Tag Archives: article

Antibacterial plants from Gayo Lues Highland

J. Pharm. Pharmacogn. Res., vol. 11, no. 1, pp. 117-128, January-February 2023.

DOI: https://doi.org/10.56499/jppres22.1526_11.1.117

Original Article

Phytochemical screening and antibacterial activity of ethnomedicinal plants from Gayo Lues Highland, Indonesia

[Cribado fitoquímico y actividad antibacteriana de plantas etnomedicinales del altiplano de Gayo Lues, Indonesia]

Hawa Purnama Celala Ary Cane1, Musri Musman2, Mustanir Yahya3, Nurdin Saidi3, Darusman Darusman4,Muhammad Nanda5, Diva Rayyan Rizki6,7, Kana Puspita2*

1Department of Chemistry, Institut Teknologi Sumatera, Lampung Selatan 35365, Indonesia.

2Department of Chemistry Education, Universitas Syiah Kuala, Banda Aceh 23111, Indonesia.

3Department of Chemistry, Universitas Syiah Kuala, Banda Aceh 23111, Indonesia.

4Department of Soil Science, Universitas Syiah Kuala, Banda Aceh 23111, Indonesia.

5Department of Marine Sciences, Universitas Syiah Kuala, Banda Aceh 23111, Indonesia.

6Medical Research Unit, School of Medicine, Universitas Syiah Kuala, Banda Aceh, 23111, Indonesia.

7Innovative Sustainability Lab, PT. Biham Riset dan Edukasi, Banda Aceh 23243, Indonesia.

*E-mail: kanapuspita@unsyiah.ac.id

Abstract

Context: Investigations of phytochemical screening and antibacterial activity were carried out on traditional medicinal plants collected in the highlands of Gayo Lues, Aceh Province, at an elevation of 1,000 meters above sea level (m.a.s.l.).

Aims: To evaluate the antibacterial activity of plants chosen based on the interview results with the traditional healers (n = 5) in Gayo Lues.

Methods: Ethanolic maceration was performed on the 12 identified ethnomedicinal plants and qualitatively screened for the phytochemical contents. Antibacterial activities against Escherichia coli ATCC 25922 and Staphylococcus aureus were tested for each extract based on the disc diffusion method, and MIC was determined using cephazolin as a reference drug.

Results: The phytochemical screening of twelve plant species showed secondary metabolites class steroids, terpenoids, flavonoids, phenols, alkaloids, and saponins. Evaluation of the antibacterial activity of the extract (10 mg/mL) yielded inhibition zone ranges of 9.8 ± 0.26 to 21.87 ± 0.47 mm for E. coli and 8.93 ± 0.9 to 23.97 ± 0.68 for S. aureus. The ethanolic extract of Garcinia macrophylla Mart stem barks showed the highest antibacterial activity, where at the lowest concentration (1.25 mg/mL), the inhibition zones were found to be 19.2 ± 0.61 and 20.72 ± 0.44 mm for E. coli and S. aureus, respectively. The MIC was found to be 1.25 mg/mL.

Conclusions: This study concludes that the twelve plant species are worthy of further investigation for novel antibacterial agent exploration.

Keywords: antibacterial; Escherichia coli; ethnomedicinal plant; Garcinia macrophylla; phytochemical; Staphylococcus aureus.

Resumen

Contexto: Se llevaron a cabo investigaciones de cribado fitoquímico y actividad antibacteriana en plantas medicinales tradicionales recolectadas en las tierras altas de Gayo Lues, provincia de Aceh, a una altitud de 1.000 metros sobre el nivel del mar (m.s.n.m.).

Objetivos: Evaluar la actividad antibacteriana de plantas elegidas basándose en los resultados de las entrevistas con los curanderos tradicionales (n = 5) de Gayo Lues.

Métodos: Se realizó una maceración etanólica de las 12 plantas etnomedicinales identificadas y se analizó cualitativamente su contenido fitoquímico. Se probó la actividad antibacteriana de cada extracto contra Escherichia coli ATCC 25922 y Staphylococcus aureus mediante el método de difusión en disco y se determinó la CMI utilizando la cefazolina como fármaco de referencia.

Resultados: El cribado fitoquímico de doce especies de plantas mostró una clase de metabolitos secundarios de esteroides, terpenoides, flavonoides, fenoles, alcaloides y saponinas. La evaluación de la actividad antibacteriana del extracto (10 mg/mL), arrojó rangos de zona de inhibición de 9,8 ± 0,26 a 21,87 ± 0,47 mm para E. coli y de 8,93 ± 0,9 a 23,97 ± 0,68 para S. aureus. El extracto etanólico de la corteza del tallo de Garcinia macrophylla Mart mostró la mayor actividad antibacteriana, ya que a la concentración más baja (1,25 mg/mL) las zonas de inhibición fueron de 19,2 ± 0,61 y 20,72 ± 0,44 mm para E. coli y S. aureus, respectivamente. La CMI fue de 1,25 mg/mL.

Conclusiones: Este estudio concluye que las doce especies de plantas son dignas de una mayor investigación para la exploración de nuevos agentes antibacterianos.

Palabras Clave: antibacteriano; Escherichia coli; fitoquímico; Garcinia macrophylla; planta etnomedicinal; Staphylococcus aureus.

Citation Format: Cane HPCA, Musman M, Yahya M, Saidi N, Darusman D, Nanda M, Rizki DR, Puspita K (2023) Phytochemical screening and antibacterial activity of ethnomedicinal plants from Gayo Lues Highland, Indonesia. J Pharm Pharmacogn Res 11(1): 117–128. https://doi.org/10.56499/jppres22.1526_11.1.117
References

Ajaib M, Khan ZUD (2012) Bischofia javanica: A new record to the Flora of Pakistan. Biologia (Pakistan) 58(1-2): 179-183.

Aththorick TA, Berutu L (2018) Ethnobotanical study and phytochemical screening of medicinal plants on Karonese people from North Sumatra, Indonesia. J Phys Conf Ser 1116(5): 052008. https://doi.org/10.1088/1742-6596/1116/5/052008

Attiq A, Jalil J, Husain K (2017) Annonaceae: Breaking the wall of inflammation. Front Pharmacol 8: 752. https://doi.org/10.3389/fphar.2017.00752

Barnes PJ (2010) Inhaled corticosteroids. Pharmaceuticals (Basel) 3(3): 514–540. https://doi.org/10.3390/ph3030514

Barreto de Deus T, Barros LSS, Mendes da Silva R, Karine da Silva Lima W, Virgens Lima DD, Dos Santos Silva A (2017) Staphylococcus aureus and Escherichia coli in Curd cheese sold in the Northeastern Region of South America. Int J Microbiol 2017: 8173741. https://doi.org/10.1155/2017/8173741

Batan A, Daniel D, Simanjuntak P (2018) Isolation of chemical active compounds antioxidant from ethyl acetate fraction of betel leaf forest  (Piper aduncum L.). J Atomik 3(2): 83–90.

Bouzada MLM, Fabri RL, Nogueira M, Konno TUP, Duarte GG, Scio E (2009) Antibacterial, cytotoxic and phytochemical screening of some traditional medicinal plants in Brazil. Pharm Biol 47(1): 44–52. https://doi.org/10.1080/13880200802411771

BPS (2015) Profile of Gayo Lues 2015, in: BAPPEDA (Ed.). Central Bureau of Statistics and Agency for Regional Development of Gayo Lues Regency, Blangkejeren.

BPS (2020) Gayo Lues Regency in Numbers. Central Bureau of Statistics of Gayo Lues, Blangkejeren.

Buru AS, Pichika MR, Neela V, Mohandas K (2014) In vitro antibacterial effects of Cinnamomum extracts on common bacteria found in wound infections with emphasis on methicillin-resistant Staphylococcus aureus. J Ethnopharmacol 153(3): 587–595. https://doi.org/10.1016/j.jep.2014.02.044

Chahal J, Ohlyan R, Kandale A, Walia A, Puri S (2011) Introduction, phytochemistry, traditional uses and biological activity of genus Piper: A review. Int J Curr Pharm Rev Res 2: 131–144.

Che Hassan NKN, Taher M, Susanti D (2018) Phytochemical constituents and pharmacological properties of Garcinia xanthochymus– a review. Biomed Pharmacother 106: 1378–1389. https://doi.org/10.1016/j.biopha.2018.07.087

Chen WC, Liou SS, Tzeng TF, Lee SL, Liu IM (2012) Wound repair and anti-inflammatory potential of Lonicera japonica in excision wound-induced rats. BMC Complement Altern Med 12: 226. https://doi.org/10.1186/1472-6882-12-226

Cowan MM (1999) Plant products as antimicrobial agents. Clin Microbiol Rev 12(4): 564–82. https://doi.org/10.1128/CMR.12.4.564

Cushnie TP, Cushnie B, Lamb AJ (2014) Alkaloids: an overview of their antibacterial, antibiotic-enhancing and antivirulence activities. Int J Antimicrob Agents 44(5): 377–386. https://doi.org/10.1016/j.ijantimicag.2014.06.001

Djufri D (2015) Leuser Ecosystem of Aceh Province as a natural laboratory for the study of biodiversity to find the raw materials of drugs. Pros Sem Nas Masy Biodiv Indon 1: 1543–1552.

Doğan A, Otlu S, Çelebi Ö, Aksu Kiliçle P, Gülmez Sağlam A, Doğan ANC, Mutlu N (2017) An investigation of antibacterial effects of steroids. Turk J Vet Anim Sci 41: 302–305. https://doi.org/10.3906/vet-1510-24

Elliott S, Brimacombe J (1987) The medicinal plants of Gunung Leuser National Park, Indonesia. J Ethnopharmacol 19(3): 285–317. https://doi.org/10.1016/0378-8741(87)90006-7

Espineli DL, Agoo EMG, Shen CC, Ragasa CY (2013) Chemical constituents of Cinnamomum iners. Chem Nat Compd 49: 932–933. https://doi.org/10.1007/s10600-013-0783-x

Fitrianti Y, Wahyudi A, Saifullah and Pratiwi NL (2012) Gayo Ethnic of Tetingi Village, Blang Pegayon Sub-District, Gayo Lues District, Nanggroe Aceh Darussalam Province. Health Research and Development Agency, Ministry of Health of the Republic of Indonesia, Surabaya.

Francis G, Kerem Z, Makkar HP, Becker K (2002) The biological action of saponins in animal systems: a review. Br J Nutr 88(6): 587–605. https://doi.org/10.1079/BJN2002725

Frickmann H, Hahn A, Berlec S, Ulrich J, Jansson M, Schwarz NG, Warnke P, Podbielski A (2019) On the etiological relevance of Escherichia coli and Staphylococcus aureus in superficial and deep infections – A hypothesis-forming, retrospective assessment. Eur J Microbiol Immunol 9(4): 124–130. https://doi.org/10.1556/1886.2019.00021

Guvenalp Z, Ozbek H, Kuruuzum-Uz A, Kazaz C, Demirezer LO (2012) Chemical constituents of Lonicera etrusca. Chem Nat Compd 48: 693–695. https://doi.org/10.1007/s10600-012-0353-7

Hammid SA, Assim Z, Ahmad F (2016) Chemical composition of Cinnamomum species collected in Sarawak. Sains Malaysiana 45: 627–632.

Harahap D, Niaci S, Mardina V, Zaura B, Qanita I, Purnama A, Puspita K, Rizki DR, Iqhrammullah M (2022) Antibacterial activities of seven ethnomedicinal plants from family Annonaceae. J Adv Pharm Technol Res 13(3): 148–153. https://doi.org/10.4103/japtr.japtr_111_22

Hemshekhar M, Sunitha K, Santhosh MS, Devaraja S, Kemparaju K, Vishwanath BS, Niranjana SR, Girish KS (2011) An overview on genus garcinia: phytochemical and therapeutical aspects. Phytochem Rev 10: 325–351. https://doi.org/10.1007/s11101-011-9207-3

Hosseinzadeh S, Jafarikukhdan A, Hosseini A, Armand R (2015) The application of medicinal plants in traditional and modern medicine: A review of Thymus vulgaris. Int J Clin Med 6: 635–642. http://dx.doi.org/10.4236/ijcm.2015.69084

Huang D, Shi F, Chai M, Li R, Li H (2015) Interspecific and intersexual differences in the chemical composition of floral scent in Glochidion species (Phyllanthaceae) in South China. J Chem 2015: 865694. https://doi.org/10.1155/2015/865694

Istiawan ND, Kastono D (2019) Effect of plant elevation on yield and quality of clove oil (Syzygium aromaticum (L.) Merr. & Perry.) in Samigaluh District, Kulon Progo. Vegetalika 8: 27–41.

Jagtap UB, Bapat VA (2010) Artocarpus: A review of its traditional uses, phytochemistry and pharmacology. J Ethnopharmacol 129: 142–166. https://doi.org/10.1016/j.jep.2010.03.031

Jambak K, Nainggolan M, Dalimunthe A (2019) Antioxidant activity of ethanolic extract and n-hexane fraction from sikkam (Bischofia javanica blume) stem bark. Asian J Pharm Res Dev 7: 1–5. https://doi.org/10.22270/ajprd.v7i2.486

Jasmine R, Selvakumar BN, Daisy P (2011) Investigating the mechanism of action of terpenoids and the effect of interfering substances on an Indian medicinal plant extract demonstrating antibacterial activity. Int J Pharm Stud Res II(II): 19–24.

Jones KE, Patel NG, Levy MA, Storeygard A, Balk D, Gittleman JL, Daszak P (2008) Global trends in emerging infectious diseases. Nature 451(7181): 990–993. https://doi.org/10.1038/nature06536

Kadhim WA, Kadhim MJ, Hameed IH (2016) Antibacterial activity of several plant extracts against Proteus species. Int J Pharm Clin Res 8: 1673–1684.

Kartika R, Sudrajat, Bustanussalam, Simanjuntak P (2019) Hydrochalcone compounds from Indonesian medicinal plant, ‘sirih hutan’, Piper aduncum (piperaceae). Rasayan J Chem 12: 1022–1026. http://dx.doi.org/10.31788/RJC.2019.1235186

Khan UA, Rahman H, Niaz Z, Qasim M, Khan J, Tayyaba, Rehman B (2013) Antibacterial activity of some medicinal plants against selected human pathogenic bacteria. Eur J Microbiol Immunol 3(4): 272–274. https://doi.org/10.1556/EuJMI.3.2013.4.6

Lastari W, Agustina ZA (2018) Meta-ethnography of delivery cultures in Indonesian. J Masy Budaya 20(1): 49–60.

Lipkovskaya NA, Barvinchenko VN, Fedyanina TV, Rugal AA (2014) Physicochemical properties of quercetin and rutin in aqueous solutions of decamethoxin antiseptic drug. Russian J Appl Chem 87: 36–41. https://doi.org/10.1134/S1070427214010054

MagadulaJoseph JJ (2014) Phytochemistry and pharmacology of the genus Macaranga: A review. J Med Plant Res 8: 489–503. https://doi.org/10.5897/JMPR2014.5396

McCarthy JF (2002) Power and interest on Sumatra’s rainforest frontier: clientelist coalitions, illegal logging and conservation in the Alas valley. J Southeast Asian Stud 33: 77–106.

Mostafa AA, Al-Askar AA, Almaary KS, Dawoud TM, Sholkamy EN, Bakri MM (2018a) Antimicrobial activity of some plant extracts against bacterial strains causing food poisoning diseases. Saudi J Biol Sci 25(2): 361–366. https://doi.org/10.1016/j.sjbs.2017.02.004

Nabavi SF, Di Lorenzo A, Izadi M, Sobarzo-Sánchez E, Daglia M, Nabavi SM (2015) Antibacterial effects of Cinnamon: From farm to food, cosmetic and pharmaceutical industries. Nutrients 7(9): 7729–7748. https://doi.org/10.3390/nu7095359

Ngule MC, Ndiku HM (2014) Antidiarrheal activity of Tetradenia riparia and Wubergia ugandensis antidiarrheal activity ethnobotanical plants in Kenya. World J Pharm Scie 2: 1180–1183.

Oliveira Filho A, Fernandes H, Assis T (2015) Lauraceae’s family: A brief review of cardiovascular effects. Int J Pharmacogn Phytochem Res 7: 22–26.

Pacheco FV, Alvarenga ICA, Junior PMR, Pinto JEBP, Avelar RdP, Alvarenga AA (2014) Growth and production of secondary compounds in monkey-pepper (Piper aduncum L.) leaves cultivated under altered ambient ligh. Australian J Crop Sci 8: 1510–1516.

Pascal OA, Bertran AEV, Esaïe T, Sylvie HAM, Eloi AY (2017) A review of the ethnomedical uses, phytochemistry and pharmacology of the Euphorbia genus. Pharma Innov J 6(1): 34–39.

Potgieter MJ, Schori M, Utteridge TMA (2016) Stemonuraceae. In: Kadereit, J.W., Bittrich, V. (Eds.), Flowering Plants. Eudicots. Springer Switzerland, pp. 367–376.

Pulingam T, Parumasivam T, Gazzali AM, Sulaiman AM, Chee JY, Lakshmanan M, Chin CF, Sudesh K (2022) Antimicrobial resistance: Prevalence, economic burden, mechanisms of resistance and strategies to overcome. Eur J Pharm Sci 170: 106103. https://doi.org/10.1016/j.ejps.2021.106103

Rizk AFM (1987) The chemical constituents and economic plants of the Euphorbiaceae. Bot J Linn Soc 94: 293–326. https://doi.org/10.1111/j.1095-8339.1987.tb01052.x

Rosita S, Wani R (2018) The relationship of social cultural and exposure to information toward use of traditional medicine for parturition at district of Teragun regency the Gayo Lues. Maj Kesehat Masy Aceh 1(2): 86–93.

Sabbineni J (2016) Phenol-An effective antibacterial agent. J Med Org Chem 3(2): 182–191.

Saetan P, Usawakesmanee W, Siripongvutikorn S (2016) Influence of hot water blanching process on phenolic profile and antioxidant activity of Cinnamomum porrectum herbal tea. Funct Foods Health Dis 6: 836–854. https://doi.org/10.31989/ffhd.v6i12.315

Shaaban HA, Ali HS, Bareh GF, Al-Khalifa ARS, Amer MM (2017) Antimicrobial activity of two polysaccharide edible films incorporated with essential oils against three pathogenic bacteria. J Appl Sci 17: 171–183. http://dx.doi.org/10.3923/jas.2017.171.183

Somashekhar M, Nayeem N, Mahesh A (2013) Botanical study of four ficus species of family Moraceae: A review. Int J Universal Pharm Bio Sci 2: 558–570.

Takos AM, Rook F (2013) Towards a molecular understanding of the biosynthesis of Amaryllidaceae alkaloids in support of their expanding medical use. Int J Mol Sci 14: 11713–11741. https://doi.org/10.3390/ijms140611713

Tetra Tech ARD (2013) Indonesia forest and climate support: conservation plan for nature of Gayo Lues district Aceh. USAID-IFACS, Jakarta, pp. 93.

Tiwari PK, Kumar B, Kaur M, Kauer G, Kaur H (2011) Phytochemical screening and extraction: A review. Int Pharm Sci 1: 98–106.

Torres-Pelayo VR, Fernandez MS, Carmona-Hernandez O, Molina-Torres J, Lozada-Garcia JA (2016) A phytochemical and ethnopharmacological review of the genus Piper: as a potent bio-insecticide. Res Rev: Res J Biol 4(2): 45–51.

Utami S (2016) Antibacterials patentability of plant Garcinia. J Kedokteran Yarsi 24: 69–79.

Wasis B (2012) Soil Properties in Natural Forest Destruction and Conversion to Agricultural Land,in Gunung Leuser National Park, North Sumatera Province. J Man Hut Trop 18: 206–212. http://dx.doi.org/10.7226/jmht.18.3.206

Wink M (2003) Evolution of secondary metabolites from an ecological and molecular phylogenetic perspective. Phytochemistry 64: 3–19. https://doi.org/10.1016/S0031-9422(03)00300-5

Xie Y, Yang W, Tang F, Chen X, Ren L (2015) Antibacterial activities of flavonoids: structure-activity relationship and mechanism. Curr Med Chem 22: 132–149. https://doi.org/10.2174/0929867321666140916113443

Zhao W, Gong XW, Duan YX, Yang J, Wu X, Jiang XJ, Xu XH, Chen YK., Yang L, Wang F, Yang XL (2019) Two new triterpenoids with antimicrobial activity from the leaves and twigs of Orophea yunnanensis. Nat Prod Res 33: 3472–3477. https://doi.org/10.1080/14786419.2018.1481843

© 2023 Journal of Pharmacy & Pharmacognosy Res

Targeted proteins for vaginal epithelial repair

J. Pharm. Pharmacogn. Res., vol. 11, no. 1, pp. 110-116, January-February 2023.

DOI: https://doi.org/10.56499/jppres22.1512_11.1.110

Original Article

Epithelial thinning in vaginal atrophy related to lowering of calcitonin gene-related protein, vascular endothelial growth factor, and nerve growth factor expressions in a menopausal rat model

[Adelgazamiento epitelial en la atrofia vaginal relacionado con la disminución de las expresiones de la proteína relacionada con el gen de la calcitonina, el factor de crecimiento endotelial vascular y el factor de crecimiento nervioso en un modelo de rata menopáusica]

An Nisa Fithri1,2*, Yuyun Yueniwati3, I Wayan Arsana4, Husnul Khotimah5, Wiwit Nurwidyaningtyas6

1Doctoral Program of Medical Sciences, Faculty of Medicine, Universitas Brawijaya, Indonesia.

2Midwifery Program, Sekolah Tinggi Ilmu Kesehatan Kendedes Malang, 65126, Indonesia.

3Department of Radiology, Public Saiful Anwar Hospital, Malang, Indonesia,

4Department of Fertility, Endocrinology and Reproduction, Obstetric and Gynecology Laboratory, Public Saiful Anwar Hospital, Faculty of Medicine, Universitas Brawijaya, Indonesia.

5Department of Pharmacology, Universitas Brawijaya, Indonesia.

6Department Molecular and Cellular Biology, Sekolah Tinggi Ilmu Kesehatan Kendedes, Malang, 65126, Indonesia.

*E-mail: teh.nisa1@gmail.com

Abstract

Context: Vaginal atrophy has been observed as a common sexual problem in post-menopausal women. The targeted protein to counteract menopause problems related to vaginal epithelial thinning is currently a research problem that has not been fully investigated.

Aims: To explore the possible mechanism underlying vaginal atrophy in rat models.

Methods: Following three-week ovariectomy (OVX), Sprague-Dawley female rats were randomly divided into two groups and orally administered estradiol for two weeks in the treated group. In parallel with this, six rats with sham surgery were used as control. Marker-related vaginal atrophy, including calcitonin gene-related protein (CGRP), vascular endothelial growth factor (VEGF), and nerve growth factor (NGF) in the vaginal wall, were compared using immunohistochemistry.

Results: OVX as a menopausal model significantly induced vaginal epithelial cell thinning and decreased the expression of CGRP, VEGF, and NGF compared with sham surgery animals (p<0.05). Estrogen replacement in OVX rats reversed the vaginal atrophic by recovering the protein expression CGRP, VEGF, and NGF (p<0.05).

Conclusions: Thus, it may be concluded that a possible mechanism underlying the OVX-induced vaginal atrophy may be related to the downregulation expression of CGRP, VEGF, and NGF in vaginal tissue.

Keywords: calcitonin gene-related protein; menopause; nerve growth factor; ovariectomy model; vaginal atrophy; vascular endothelial growth factor.

Resumen

Contexto: Se ha observado que la atrofia vaginal es un problema sexual común en las mujeres posmenopáusicas. La proteína dirigida a contrarrestar los problemas de la menopausia relacionados con el adelgazamiento del epitelio vaginal es actualmente un problema de investigación que no se ha investigado completamente.

Objetivos: Explorar el posible mecanismo subyacente a la atrofia vaginal en modelos de rata.

Métodos: Tras una ovariectomía (OVX) de tres semanas, se dividieron aleatoriamente ratas hembras Sprague-Dawley en dos grupos y se les administró estradiol por vía oral durante dos semanas en el grupo tratado. Paralelamente, se utilizaron como control seis ratas con cirugía simulada. Se compararon mediante inmunohistoquímica los marcadores de atrofia vaginal, como la proteína relacionada con el gen de la calcitonina (CGRP), el factor de crecimiento endotelial vascular (VEGF) y el factor de crecimiento nervioso (NGF) en la pared vaginal.

Resultados: La OVX como modelo menopáusico indujo significativamente el adelgazamiento de las células epiteliales vaginales y disminuyó la expresión de CGRP, VEGF y NGF en comparación con los animales sometidos a cirugía simulada (p<0,05). El reemplazo de estrógenos en las ratas OVX revirtió la atrofia vaginal recuperando la expresión de proteínas CGRP, VEGF y NGF (p<0,05).

Conclusiones: Por lo tanto, se puede concluir que un posible mecanismo subyacente a la atrofia vaginal inducida por la OVX puede estar relacionado con la disminución de la expresión de CGRP, VEGF y NGF en el tejido vaginal.

Palabras Clave: atrofia vaginal; factor de crecimiento endotelial vascular; factor de crecimiento nervioso; ; menopausia; modelo de ovariectomía; proteína relacionada con el gen de la calcitonina.

Citation Format: Fithri AN, Yueniwati Y, Arsana IW, Khotimah H, Nurwidyaningtyas W (2023) Epithelial thinning in vaginal atrophy related to lowering of calcitonin gene-related protein, vascular endothelial growth factor, and nerve growth factor expressions in a menopausal rat model. J Pharm Pharmacogn Res 11(1): 110–116. https://doi.org/10.56499/jppres22.1512_11.1.110
References

Ali A, Syed SM, Jamaluddin M, Colino-Sanguino Y, Gallego-Ortega, D, Tanwar PS (2020) Cell lineage tracing identifies hormone-regulated and Wnt-responsive vaginal epithelial stem cells. Cell Rep 30(5): 1463–1477.e7. https://doi.org/10.1016/j.celrep.2020.01.003

Armayanti LY, Wulansari NT (2020) Regulation of sex steroid sex hormones on calcitonin gene-related peptide (CGRP)’s mRNA expression in vaginal mucosa epitel of bilateral ovarectomized Wistar rats. Biomed Pharmacol J 13(1): 263–268. https://dx.doi.org/10.13005/bpj/1885

Bleibel B, Nguyen H (2022) Vaginal Atrophy. [Updated 2022 Jul 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK559297/

Chow C, Che S, Qin HY, Kwan HY, Bian ZX, Wong H (2019) From psychology to physicality: How nerve growth factor transduces early life stress into gastrointestinal motility disorders later in life. Cell Cycle 18(16): 1824–1829. https://doi.org/10.1080/15384101.2019.1637203

Cora MC, Kooistra L, Travlos G (2015) Vaginal cytology of the laboratory rat and mouse: Review and criteria for the staging of the estrous cycle using stained vaginal smears. Toxicol Pathol 43: 776–793. https://doi.org/10.1177/0192623315570339

Dos Santos CCM, Uggioni MLR, Colonetti T, Colonetti L, Grande AJ, Da Rosa MI (2021) Hyaluronic acid in postmenopause vaginal atrophy: A systematic review. J Sex Med 18(1): 156–166. https://doi.org/10.1016/j.jsxm.2020.10.016

Edwards D, Panay N (2016) Treating vulvovaginal atrophy/genitourinary syndrome of menopause: How important is vaginal lubricant and moisturizer composition? Climacteric 19(2): 151–161. https://doi.org/10.3109/13697137.2015.1124259

Gao H, Xiao M, Bai H, Zhang Z (2017) Sexual function and quality of life among patients with endometrial cancer after surgery. Int J Gynecol Cancer 27(3): 608–612. https://doi.org/10.1097/IGC.0000000000000905

Geller EJ, Bretschneider CE, Wu JM, Kenton K, Matthews CA (2021) Sexual function after minimally invasive total hysterectomy and sacrocolpopexy. J Minim Invasive Gynecol 28(9): 1603–1609. https://doi.org/10.1016/j.jmig.2021.01.021

Handy AB, Meston CM (2021) An objective measure of vaginal lubrication in women with and without sexual arousal concerns. J Sex Marital Ther 47(1): 32–42. https://doi.org/10.1080/0092623X.2020.1801542

Isaza PG (2019) Use of growth factors for vulvo/vaginal bio-stimulation. Surg Technol Int 15(34): 269–273.

Karppinen JE, Törmäkangas T, Kujala UM, Sipilä S, Laukkanen J, Aukee P, Kovanen V, Laakkonen EK (2022) Menopause modulates the circulating metabolome: evidence from a prospective cohort study. Eur J Prev Cardiol 29(10): 1448–1459. https://doi.org/10.1093/eurjpc/zwac060

Kasap B, Kasap Ş Vatansever S, Kendirci R, Yılmaz O, Ćaşlır M, Edgṻnlṻ T, Akın MN (2019) Effects of adipose and bone marrow-derived mesenchymal stem cells on vaginal atrophy in a rat menopause model. Gene 711: 143937. https://doi.org/10.1016/j.gene.2019.06.027

Laumann EO, Paik A, Rosen RC (1999) Sexual dysfunction in the United States: Prevalence and predictors. JAMA 281(6): 537–544. https://doi.org/10.1001/jama.281.6.537

Li S, Herrera GG, Tam KK, Lizarraga JS, Beedle MT, Winuthayanon W (2018) Estrogen action in the epithelial cells of the mouse vagina regulates neutrophil infiltration and vaginal tissue integrity. Sci Rep 8(1): 11247. https://doi.org/10.1038/s41598-018-29423-5

Liu H, Zhong L, Zhang Y, Liu X, Li J (2018) Rutin attenuates cerebral ischemia-reperfusion injury in ovariectomized rats via estrogen-receptor-mediated BDNF-TrkB and NGF-TrkA signaling. Biochem Cell Biol 96(5): 672–681. https://doi.org/10.1139/bcb-2017-0209

Molnár I (2020) Interactions among thyroid hormone (FT4), chemokine (MCP-1) and neurotrophin (NGF-β) levels studied in Hungarian post-menopausal and obese women. Cytokine 127: 154948. https://doi.org/10.1016/j.cyto.2019.154948

Mueck AO, Ruan X, Prasauskas V, Grob P, Ortmann O (2018) Treatment of vaginal atrophy with estriol and Lactobacilli combination: A clinical review. Climateric 21(2): 140–147. https://doi.org/10.1080/13697137.2017.1421923

Nakamura T, Miyagawa S, Katsu Y, Sato T, Iguchi T, Ohta Y (2012) Sequential changes in the expression of Wnt- and Notch-related genes in the vagina and uterus of ovariectomized mice after estrogen exposure. In Vivo 26(6): 899-906.

Nappi R, Martini E, Cucinella L, Martella S, Tiranini L, Inzoli A, Brambilla E, Bosoni D, Cassani C, Gardella B (2019) Addressing vulvovaginal atrophy (VVA)/genitourinary syndrome of menopause (GSM) for healthy aging in women. Front Endocrinol 10: 561. https://doi.org/10.3389/fendo.2019.00561

Naumova I, Castelo-Branco C (2018) Current treatment options for post-menopausal vaginal atrophy. Int J Womens Health 10: 387–395. https://doi.org/10.2147/IJWH.S158913

Oliveira MA, Lima WG, Schettini DA, Tilelli CQ, Chaves VE (2019) Is calcitonin gene-related peptide a modulator of menopausal vasomotor symptoms? Endocrine 63(2): 193–203. https://doi.org/10.1007/s12020-018-1777-z

Palacios S, Nappi R, Bruyniks N, Particco M, Panay N, EVES Study Investigators (2018) The European Vulvovaginal Epidemiological Survey (EVES): Prevalence, symptoms and impact of vulvovaginal atrophy of menopause. Climacteric 21(3): 286–291. https://doi.org/10.1080/13697137.2018.1446930

Pan Z, Wen S, Qiao X, Yang M, Shen X, Xu L (2022) Different regimens of menopausal hormone therapy for improving sleep quality: a systematic review and meta-analysis. Menopause 29(5): 627–635. https://doi.org/10.1097/GME.0000000000001945

Pérez-Herrezuelo I, Aibar-Almazán A, Martínez-Amat A, Fábrega-Cuadros R, Díaz-Mohedo E, Wangensteen R, Hita-Contreras F (2020) Female sexual function and its association with the severity of menopause-related symptoms. Int J Environ Res Public Health 17(19): 7235. https://doi.org/10.3390/ijerph17197235

Shafaat S, Mangir N, Chapple C, MacNeil S, Hearnden V (2022) A physiologically relevant, estradiol-17β[E2]-responsive in vitro tissue-engineered model of the vaginal epithelium for vaginal tissue research. Neurourol Urodyn 41(4): 905–917. https://doi.org/10.1002/nau.24908

Shang X, Zhang L, Jin R, Yang H, Tao H (2021) Estrogen regulation of the expression of pain factor NGF in rat chondrocytes. J Pain Res 9(14): 931–940. https://doi.org/10.2147/JPR.S297442

Shen Z, Fahey JV, Bodwell JE, Rodriguez-Garcia M, Rossoll RM, Crist SG, Patel MV, Wira CR (2013) Estradiol regulation of nucleotidases in female reproductive tract epithelial cells and fibroblasts. PLoS One 8(7): e69854. https://doi.org/10.1371/journal.pone.0069854

Tsai T, Yeh C, Hwang T (2011) Female sexual dysfunction: physiology, epidemiology, classification, evaluation and treatment. Urol Sci 22(1): 7–13. https://doi.org/10.1016/S1879-5226(11)60002-X

Winuthayanon W, Lierz SL, Delarosa KC, Sampels SR, Donoghue LJ, Hewitt SC, Korach KS (2017) Juxtacrine activity of estrogen receptor α in uterine stromal cells is necessary for estrogen-induced epithelial cell proliferation. Sci Rep 7(1): 8377. https://doi.org/10.1038/s41598-017-07728-1

Yin QZ, Lu H, Li LM, Yie SM, Hu X, Liu ZB, Zheng X, Cao S, Yao ZY (2013) Impacts of You Gui Wan on the expression of estrogen receptors and angiogenic factors in OVX‑rat vagina: A possible mechanism for the trophic effect of the formula on OVX‑induced vaginal atrophy. Mol Med Rep 8(5): 1329–1336. https://doi.org/10.3892/mmr.2013.1670

© 2023 Journal of Pharmacy & Pharmacognosy Research

Bioadsorption of silver ions by chitin derivatives

J. Pharm. Pharmacogn. Res., vol. 11, no. 1, pp. 101-109, January-February 2023.

DOI: https://doi.org/10.56499/jppres22.1529_11.1.101

Original Article

Bioadsorption of silver ions by calcareous chitin, chitin and chitosan

[Bioadsorción de iones de plata por quitina calcárea, quitina y quitosano]

John Jáuregui-Nongrados1, Angel T. Alvarado2*, Miguel Mucha1, Ana M. Muñoz3, Haydee Chávez4, Aura Molina-Cabrera4, Pompeyo A. Cuba-García4, Elizabeth J. Melgar-Merino4, Mario Bolarte-Arteaga5, Jaime A. Mori-Castro6

1Environmental Engineering, San Ignacio de Loyola University, La Molina 15024, Lima, Peru.

2International Research Network of Pharmacology and Precision Medicine (REDIFMEP), San Ignacio de Loyola University, La Molina 15024, Lima, Peru.

3Institute of Food Science and Nutrition, ICAN, San Ignacio de Loyola University, La Molina 15024, Lima, Peru.

4Faculty of Pharmacy and Biochemistry, San Luis Gonzaga National University of Ica, 11004, Ica, Peru.

5Human Medicine, Continental University, Los Olivos 15304, Lima, Peru.

6Professional School of Nursing, Faculty of Health Sciences, Norbert Wiener University, Lince 15046, Lima, Peru.

*E-mail: angel.alvarado@usil.pe

Abstract

Context: Calcareous chitin, chitin, chitosan, and their modifications are used as bioadsorbents of metals and dyes that cause environmental pollution, endocrine disruption, and human diseases.

Aims: To evaluate the selective bioadsorption of silver ions (Ag+) by calcareous chitin, chitin, and chitosan.

Methods: Experimental and prospective study. The presence of functional groups of the bioadsorbents was identified by Fourier-transformed infrared spectroscopy (FT-IR), 1H-NMR spectroscopy and scanning electron microscopy (SEM). The Langmuir, Freundlich, and Elovich models were applied to describe the adsorption capacity of bioadsorbents according to granule size (20-40, 40-60, 60-80 meshes) and temperature (10, 20, and 30°C).

Results: The FT-IR spectrum of calcareous chitin indicates the presence of carbonate (CO3= 1420 cm-1), amide III (1313 cm-1), –OH groups (3441.90 cm-1), and pyranose structure (952.83 cm-1); chitin has –OH groups (3441.90 cm-1), NH (3268 cm-1), amide I (1654 cm-1) and II (1559 cm-1); chitosan has –OH groups (3419.90 cm-1), –NH (3200 cm-1), amide I (1712.18 cm-1), –NH2 (1654.46 cm-1), amide III (1317.11 cm-1) and pyranose structure (1070.12 cm-1 and 1031 cm-1). The Langmuir model indicates greater bioadsorption of Ag+ ions at smaller particle sizes (60-80 = 0.25-0.18 mm) and at a temperature of 20-30°C.

Conclusions: The bioadsorption of silver ions (Ag+) by chitosan is greater with respect to calcareous chitin and chitin; the Langmuir model fits for the Ag+ isotherm and suggests that the process is controlled by physisorption.

Keywords: bioadsorption; calcareous chitin; chitin; chitosan; silver ions.

Resumen

Contexto: La quitina calcárea, quitina, quitosano y sus modificaciones se utilizan como bioadsorbentes de metales y tintes causantes de la contaminación medioambiental, disrupción endocrina y enfermedades en humanos.

Objetivos: Evaluar la bioadsorción selectiva de iones plata (Ag+) por quitina calcárea, quitina y quitosano.

Métodos: Estudio experimental y prospectivo. Se identificó la presencia de grupos funcionales de los bioadsorbentes por espectroscopia infrarroja transformada de Fourier (FT-IR), espectroscopia 1H-RMN y por microscopía electrónica de barrido (SEM). Se aplicó los modelos de Langmuir, Freundlich, y Elovich, para describir la capacidad de adsorción de los bioadsorbentes de acuerdo al tamaño del granulo (20-40, 40-60, 60-80 meshes) y temperatura (10, 20 y 30°C).

Resultados: El espectro FT-IR de la quitina calcárea indica presencia de carbonato (CO3= 1420 cm-1), amida III (1313 cm-1), grupos –OH (3441,90 cm-1) y estructura piranósica (952,83 cm-1); quitina presenta grupos –OH (3441,90 cm-1), NH (3268 cm-1), amida I (1654cm-1) y II (1559 cm-1); quitosano se identifica grupos –OH (3419.90 cm-1), –NH (3200 cm-1), amida I (1712.18 cm-1), –NH2 (1654.46 cm-1), amida III (1317.11 cm-1) y estructura piranósica (1070.12 cm-1 y 1031 cm-1). El modelo de Langmuir indica mayor bioadsorción de iones Ag+ a menor tamaño de partícula (60-80 = 0.25-0.18 mm) y a una temperatura de 20-30°C.

Conclusiones: La bioadsorción de iones de plata (Ag+) por quitosano es mayor respecto a quitina calcárea y quitina; el modelo de Langmuir se ajusta para la isoterma de Ag+ y sugiere que el proceso está controlado por fisisorción.

Palabras Clave: bioadsorción; iones plata; quitina; quitina calcárea; quitosano.

Citation Format: Jáuregui J, Alvarado AT, Mucha M, Muñoz AM, Chávez H, Molina A, Cuba PA, Melgar EJ, Bolarte M, Mori JA (2023) Bioadsorption of silver ions by calcareous chitin, chitin and chitosan. J Pharm Pharmacogn Res 11(1): 101–109. https://doi.org/10.56499/jppres22.1529_11.1.101
References

Al-Wabel MI, Ahmad M, Usman ARA, Al-Farraj ASF (2021) Designing chitosan based magnetic beads with Conocarpus waste-derived biochar for efficient sulfathiazole removal from contaminated water. Saudi J Biol Sci 28(11): 6218–6229. https://doi.org/10.1016/j.sjbs.2021.06.072

Azizkhani S, Hussain SA, Abdullah N, Ismail MHS, Mohammad AW (2021) Synthesis and application of functionalized Graphene oxide-silica with chitosan for removal of Cd (II) from aqueous solution. J Environ Health Sci Eng 19(1): 491–502. https://doi.org/10.1007/s40201-021-00622-z

Banisheykholeslami F, Hosseini M, Najafpour Darzi G (2021) Design of PAMAM grafted chitosan dendrimers biosorbent for removal of anionic dyes: Adsorption isotherms, kinetics and thermodynamics studies. International J Biol Macromol 177: 306–316. https://doi.org/10.1016/j.ijbiomac.2021.02.118

Basova TV, Vikulova ES, Dorovskikh SI, Hassan A, Morozova NB (2021) The use of noble metal coatings and nanoparticles for the modification of medical implant materials. Maters Des 204: 109672. https://doi.org/10.1016/j.matdes.2021.109672

Ding Y, Zhang S, Liu B, Zheng H, Chang C, Ekberg C (2019) Recovery of precious metals from electronic waste and spent catalysts: A review. Resour Conserv Recycl 141: 284–298. https://doi.org/10.1016/j.resconrec.2018.10.041

El-Naggar ME, Radwan EK, Rashdan HRM, El-Wakeel ST, Koryam AA, Sabt A (2022) Simultaneous removal of Pb2+ and direct red 31 dye from contaminated water using N-(2-hydroxyethyl)-2-oxo-2H-chromene-3-carboxamide loaded chitosan nanoparticles. RSC Adv 12(29): 18923–18935. https://doi.org/10.1039/D2RA02526D

Gao Y, Zhou Y, Wang H, Lin W, Wang Y, Sun D, Hong J, Li, Q (2013) Simultaneous silver recovery and cyanide removal from electroplating wastewater by pulse current electrolysis using static cylinder electrodes. Ind Eng Chem Res 52(17): 5871–5879. https://doi.org/10.1021/ie301731g

Golnaraghi Ghomi A, Asasian-Kolur N, Sharifian S, Golnaraghi A (2020) Biosorpion for sustainable recovery of precious metals from wastewater. J Environ Chem Eng 8(4): 103996. https://doi.org/10.1016/j.jece.2020.103996

Goulet PJG, Lennox RB (2010) New insights into Brust−Schiffrin metal nanoparticle synthesis. J Am Chem Soc 132: 9582–9584. https://doi.org/10.1021/ja104011b

Hsu E, Barmak K, West AC, Park AHA (2019) Advancements in the treatment and processing of electronic waste with sustainability: A review of metal extraction and recovery technologies. Green Chem 21(5): 919–936. https://doi.org/10.1039/C8GC03688H

Jiang Y, Fu C, Wu S, Liu G, Guo J, Su Z (2017) Determination of the deacetylation degree of chitooligosaccharides. Mar Drugs 15(11): 332. https://doi.org/10.3390/md15110332

Khayrova A, Lopatin S, Varlamov V (2021) Obtaining chitin, chitosan and their melanin complexes from insects. Int J of Biol Macromol 167: 1319–1328. https://doi.org/10.1016/j.ijbiomac.2020.11.086

Kumar D, Niraula P, Aryal H, Budhathoki B, Phuyal S, Marahatha R, Subedi K (2022) Plant-mediated green synthesis of Ag NPs and their possible applications: A critical review. J Nanotechnol 2022: 2779237. https://doi.org/10.1155/2022/2779237

Lee SH, Jun BH (2019) Silver nanoparticles: Synthesis and application for nanomedicine. Int J Mol Sci 20(4): 865. https://doi.org/10.3390/ijms20040865

Li Q, Mao Q, Li M, Zhang S, He G, Zhang W (2020) Cross-linked chitosan microspheres entrapping silver chloride via the improved emulsion technology for iodide ion adsorption. Carbohydr Polym 234: 115926. https://doi.org/10.1016/j.carbpol.2020.115926

Mao J, Lin S, Lu XJ, Wu XH, Zhou T, Yun YS (2020) Ion-imprinted chitosan fiber for recovery of Pd(II): Obtaining high selectivity through selective adsorption and two-step desorption. Environ Res 182: 108995. https://doi.org/10.1016/j.envres.2019.108995

Mousavi SM, Hashemi SA, Ghasemi Y, Atapour A, Amani AM, Savar Dashtaki A, Babapoor A, Arjmand O (2018) Green synthesis of silver nanoparticles toward bio and medical applications: Review study. Artif Cells Nanomed Biotechnol 46(Supp. 3): S855–S872. https://doi.org/10.1080/21691401.2018.1517769

Murcia-Salvador A, Pellicer JA, Fortea MI, Gómez-López VM, Rodríguez-López MI, Núñez-Delicado E, Gabaldón JA (2019) Adsorption of direct blue 78 using chitosan and cyclodextrins as adsorbents. Polymers 211(6): 1003. https://doi.org/10.3390/polym11061003

Oliver AL, Oliver A (2017) La nanotecnología, la arquitectura y el arte. Mundo Nano 10(19): 117–128. https://doi.org/10.22201/ceiich.24485691e.2017.19.57719

Pascu B, Ardean C, Davidescu CM, Negrea A, Ciopec M, Duțeanu N, Negrea P, Rusu G (2020) Modified chitosan for silver recovery-kinetics, thermodynamic, and equilibrium studies. Materials 13(3): 657. https://doi.org/10.3390/ma13030657

Pavlova O, Trusova M (2021) Optimisation of conditions for deacetylation of chitin-containing raw materials. Food Sci Technol 15(3): 63–70. https://doi.org/10.15673/fst.v15i3.2152

Petrova YS, Pestov AV, Usoltseva MK, Neudachina LK (2015) Selective adsorption of silver(I) ions over copper(II) ions on a sulfoethyl derivative of chitosan. J Hazard Mater 299: 696–701. https://doi.org/10.1016/j.jhazmat.2015.08.001

Sadiq AC, Rahim NY, Suah FBM (2020) Adsorption and desorption of malachite green by using chitosan-deep eutectic solvents beads. Int J Biol Macromol 164: 3965–3973. https://doi.org/10.1016/j.ijbiomac.2020.09.029

Sergeevna KA, Leonidovna CM, Konstantinovna NL, Sergeevich PI (2020) Method of adsorption-atomic-absorption determination of silver (I) using a modified polysiloxane. React Funct Polym 152: 104596. https://doi.org/10.1016/j.reactfunctpolym.2020.104596

Sharef HY, Fakhre NA (2022) Rapid adsorption of some heavy metals using extracted chitosan anchored with new aldehyde to form a Schiff base. PLoS One 17(9): e0274123. https://doi.org/10.1371/journal.pone.0274123

Soto-Vazquez R, Záyago E, Maldonado LA (2022) Gobernanza de la nanomedicina: Una revisión sistemática. Mundo Nano 15(28): 1e–25e. https://doi.org/10.22201/ceiich.24485691e.2022.28.69682

Sportelli MC, Izzi M, Kukushkina EA, Hossain SI, Picca RA, Ditaranto N, Cioffi N (2020) Can nanotechnology and materials science help the fight against SARS-CoV-2? Nanomaterials (Basel) 10(4): 802. https://doi.org/10.3390/nano10040802

Terzioğlu D, Dalgıç Bozyiğit G, Fırat Ayyıldız M, Chormey DS, Bakırdere S (2021) Combination of slotted quartz tube flame atomic absorption spectrometry and dispersive liquid–liquid microextraction for the trace determination of silver in electroplating rinse bath. Anal Lett 54: 761–771. https://doi.org/10.1080/00032719.2020.1780603

Wang Z, Li Q, Xu L, Ma J, Wei B, An Z, Wu W, Liu S (2020) Silver nanoparticles compromise the development of mouse pubertal mammary glands through disrupting internal estrogen signaling. Nanotoxicology 14(6): 740–756. https://doi.org/10.1080/17435390.2020.1755470

Weißpflog J, Vehlow D, Müller M, Kohn B, Scheler U, Boye S, Schwarz S (2021) Characterization of chitosan with different degree of deacetylation and equal viscosity in dissolved and solid state-Insights by various complimentary methods. Int J Biol Macromol 171: 242–261. https://doi.org/10.1016/j.ijbiomac.2021.01.010

Zhao F, Peydayesh M, Ying Y, Ping J, Mezzenga R (2020) Transition metal dichalcogenide-silk nanofibril membrane for one-step water purification and precious metals recovery. ACS Appl Mater Interfaces 12(21): 24521–24530 https://doi.org/10.1021/acsami.0c07846

© 2023 Journal of Pharmacy & Pharmacognosy Research

Adverse cardiac events following mRNA COVID-19 vaccination

J. Pharm. Pharmacogn. Res., vol. 11, no. 1, pp. 76-100, January-February 2023.

DOI: https://doi.org/10.56499/jppres22.1524_11.1.76

Review

Adverse cardiac events following mRNA COVID-19 vaccination: A systematic review and meta-analysis

[Eventos cardíacos adversos tras la vacunación con COVID-19 ARNm: Una revisión sistemática y metaanálisis]

Eka Arum Cahyaning Putri1*, Misbakhul Munir1, Hayuris Kinandita Setiawan1, Lilik Herawati1, Gadis Meinar Sari1, Citrawati Dyah Kencono Wungu1, Hendri Susilo2,3, Henry Sutanto4

1Department of Medical Physiology and Biochemistry, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.

2Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.

3Department of Cardiology and Vascular Medicine, Universitas Airlangga Hospital, Surabaya, Indonesia.

4Department of Cardiology, CARIM School for Cardiovascular Diseases, Maastricht University, 6211 Maastricht, The Netherlands.

*E-mail: eka-arum-cp@fk.unair.ac.id

Abstract

Context: Although have been proven able to control the prevalence of coronavirus disease-19 (COVID-19), Pfizer-BioNTech and Moderna COVID-19 vaccines are reported to have possible side effects on the heart.

Aims: To know the magnitude of adverse events in the cardiac after messenger ribonucleic acid (mRNA)-based vaccination.

Methods: An electronic search in PubMed, Web of Science, Scopus, and Ebsco/Cinahl was performed. The keywords were: “COVID-19 vaccine”, “SARS-CoV-2 vaccine”, “myocarditis”, “myopericarditis”, “pericarditis”, “myocardial infarction”, and “myocardial injury”. The electronic search was updated until March 2022. STATA/MP Statistical Software: Release 14 (StataCorp LLC, College Station, Texas) was used in this study to perform a meta-analysis of a random-effect for myocarditis, pericarditis, myocarditis, myocardial infarction, and myocardial injury.

Results: Twenty-one case reports/case series studies with a total of 62 individuals who had been vaccinated against COVID-19 mRNA (Pfizer-BioNTech and Moderna) were included in the systematic review. Whereas seven observational cohort studies had 170,053,333 people who had been vaccinated, 245 of whom had myocarditis. In addition, two observational cohort studies with 13,948,595 vaccinated individuals, 16 of whom developed pericarditis. There was only one observational cohort study that had a total of 7,183,889 people who had been vaccinated and 11 had myopericarditis. Based on the pooled incidence, the result is <0.002%.

Conclusions: The Pfizer-BioNTech and Moderna vaccines have a low incidence of myocarditis. Men are more likely to develop post-COVID-19 myocarditis with an average age of 22 years and in the age range of 21-40 years. The type of mRNA COVID-19 vaccine that causes myocarditis the most is Pfizer. The diagnosis of myocarditis is mostly made by troponin examination. COVID-19 mRNA vaccination has a low incidence of myocarditis.

Keywords: cardiac disease; cardiac events; COVID-19; mRNA vaccines; SARS-CoV-2.

Resumen

Contexto: Aunque se ha demostrado que pueden controlar la prevalencia de la enfermedad por coronavirus-19 (COVID-19), se ha informado que las vacunas contra COVID-19 de Pfizer-BioNTech y Moderna tienen posibles efectos secundarios sobre el corazón.

Objetivos: Conocer la magnitud de los efectos adversos en el corazón tras la vacunación basada en ácido ribonucleico mensajero (ARNm).

Métodos: Se realizó una búsqueda electrónica en PubMed, Web of Science, Scopus y Ebsco/Cinahl. Las palabras clave fueron: “vacuna COVID-19”, “vacuna SARS-CoV-2”, “miocarditis”, “miopericarditis”, “pericarditis”, “infarto de miocardio” y “lesión miocárdica”. La búsqueda electrónica se actualizó hasta marzo de 2022. Software estadístico STATA/MP: Versión 14 (StataCorp LLC, College Station, Texas) se utilizó en este estudio para realizar un metanálisis de efecto aleatorio para miocarditis, pericarditis, miocarditis, infarto de miocardio y lesión miocárdica.

Resultados: Se incluyeron en la revisión sistemática 21 estudios de informes de casos/series de casos con un total de 62 individuos que habían sido vacunados contra COVID-19 ARNm (Pfizer-BioNTech y Moderna). Mientras que siete estudios observacionales de cohortes contaban con 170.053.333 personas que habían sido vacunadas, 245 de las cuales presentaron miocarditis. Además, dos estudios observacionales de cohortes con 13.948.595 personas vacunadas, 16 de las cuales desarrollaron pericarditis. Sólo hubo un estudio observacional de cohortes con un total de 7.183.889 personas vacunadas y 11 tuvieron miopericarditis. Basándose en la incidencia agrupada, el resultado es <0,002%.

Conclusiones: Las vacunas Pfizer-BioNTech y Moderna tienen una baja incidencia de miocarditis. Los hombres son más propensos a desarrollar miocarditis post-COVID-19 con una edad media de 22 años y en el rango de edad de 21-40 años. El tipo de vacuna COVID-19 de ARNm que causa más miocarditis es Pfizer. El diagnóstico de la miocarditis se realiza principalmente mediante el examen de troponina. La vacunación con ARNm COVID-19 tiene una baja incidencia de miocarditis.

Palabras Clave: enfermedad cardiaca; eventos cardiacos; COVID-19; vacunas de ARNm; SARS-CoV-2.

Citation Format: Putri EAC, Munir M, Setiawan HK, Herawati L, Sari GM, Wungu CDK, Susilo H, Sutanto H (2023) Adverse cardiac events following mRNA COVID-19 vaccination: A systematic review and meta-analysis. J Pharm Pharmacogn Res 11(1): 76–100. https://doi.org/10.56499/jppres22.1524_11.1.76
References

Ammirati E, Cipriani M, Moro C, Raineri C, Pini D, Sormani P, Mantovani R, Varrenti M, Pedrotti P, Conca C, Mafrici A, Grosu A, Briguglia D, Guglielmetto S, Perego GB, Colombo S, Caico SI, Giannattasio C, Maestroni A, Carubelli V, Metra M, Lombardi C, Campodonico J, Agostoni P, Peretto G, Scelsi L, Turco A, Di Tano G, Campana C, Belloni A, Morandi F, Mortara A, Cirò A, Senni M, Gavazzi A, Frigerio M, Oliva F, Camici PG; Registro Lombardo delle Miocarditi (2018) Clinical presentation and outcome in a contemporary cohort of patients with acute myocarditis: Multicenter Lombardy Registry. Circulation 138(11): 1088–1099. https://doi.org/10.1161/CIRCULATIONAHA.118.035319

Ammirati E, Frigerio M, Adler E, Basso C, Birnie D, Brambatti M (2020) Management of acute myocarditis and chronic inflammatory cardiomyopathy: An expert consensus document. Circ Heart Fail 13(11): e007405. https://doi.org/10.1161/CIRCHEARTFAILURE.120.007405

Anzini M, Merlo M, Sabbadini G, Barbati G, Finocchiaro G, Pinamonti B, Salvi A, Perkan A, Di Lenarda A, Bussani R, Bartunek J, Sinagra G (2013) Long-term evolution and prognostic stratification of biopsy-proven active myocarditis. Circ Res 128: 2384–2394. https://doi.org/10.1161/CIRCULATIONAHA.113.003092

 Aquaro GD, Perfetti M, Camastra G, Monti L, Dellegrottaglie S, Moro C, Pepe A, Todiere G, Lanzillo C, Scatteia A, Di Roma M, Pontone G, Perazzolo Marra M, Barison A, Di Bella G (2017) Cardiac magnetic resonance working group of the Italian Society of Cardiology. Cardiac MR with late gadolinium enhancement in acute myocarditis with preserved systolic function: ITAMY study. J Am Coll Cardiol 70: 1977–1987. https://doi.org/10.1016/j.jacc.2017.08.044

Aromataris E, Munn Z (Editors) (2020) JBI Manual for Evidence Synthesis. JBI. https://doi.org/10.46658/JBIMES-20-01

Arvin AM, Fink K, Schmid MA, Cathcart A, Spreafico R, Havenar-Daughton C, Lanzavecchia A, Corti D, Virgin HW (2020) A perspective on potential antibody-dependent enhancement of SARS-CoV-2. Nature 584: 353–363. https://doi.org/10.1038/s41586-020-2538-8

Barda N, Dagan N, Ben-Shlomo Y, Kepten E, Waxman J, Ohana R, Hernán MA, Lipsitch M, Kohane I, Netzer D, Reis BY, Balicer RD (2021) Safety of the BNT162b2 mRNA COVID-19 vaccine in a nationwide setting. New Engl J Med 385(12): 1078–1090. https://doi.org/10.1056/NEJMoa2110475

Bartok E, Hartmann G (2020) Immune sensing mechanisms that discriminate self from altered self and foreign nucleic acids. Immunity 53: 54–77. https://doi.org/10.1016/j.immuni.2020.06.014

Bass A, Patterson JH, Adams KF Jr (2010) Perspective on the clinical application of troponin in heart failure and states of cardiac injury. Heart Fail Rev 15(4): 305–317. https://doi.org/10.1007/s10741-008-9124-8

Biesbroek PS, Beek AM, Germans T, Niessen HW, van Rossum AC (2015) Diagnosis of myocarditis: Current state and future perspectives. Int J Cardiol 191: 211–219. https://doi.org/10.1016/j.ijcard.2015.05.008

Bleier J, Vorderwinkler KP, Falkensammer J, Mair P, Dapunt O, Puschendorf B, Mair J (1998) Different intracellular compartmentations of cardiac troponins and myosin heavy chains: a causal connection to their different early release after myocardial damage. Clin Chem 44: 1912–1918.

Boehmer TK, Kompaniyets L, Lavery AM, Hsu J, Ko JY, Yusuf H, Romano SD, Gundlapalli AV, Oster ME, Harris AM (2021) Association between COVID-19 and myocarditis using hospital-based administrative data – United States, March 2020-January 2021. MMWR Morb Mortal Wkly Rep 70(35): 1228–1232. http://dx.doi.org/10.15585/mmwr.mm7035e5

Buttà C, Zappia L, Laterra G, Roberto M (2020) Diagnostic and prognostic role of electrocardiogram in acute myocarditis: A comprehensive review. Ann Noninvasive Electrocardiol 25(3): e12726. https://doi.org/10.1111/anec.12726

Caforio AL, Calabrese F, Angelini A, Tona F, Vinci A, Bottaro S, Ramondo A, Carturan E, Iliceto S, Thiene G, Daliento L (2007) A prospective study of biopsy-proven myocarditis: prognostic relevance of clinical and aetiopathogenetic features at diagnosis. Eur Heart J 28(11): 1326–1333. https://doi.org/10.1093/eurheartj/ehm076

Cai C, Peng Y, Shen E, Huang Q, Chen Y, Liu P, Guo C, Feng Z, Gao L, Zhang X, Gao Y, Liu Y, Han Y, Zeng S, Shen H (2021) A comprehensive analysis of the efficacy and safety of COVID-19 vaccines. Mol Ther 29(9): 2794–2805. https://doi.org/10.1016/j.ymthe.2021.08.001

CDC (2021a) Centres for Diseases Control and Prevention (CDC). Local Reactions, Systemic Reactions, Adverse Events, and Serious Adverse Events: Moderna COVID-19 Vaccine. https://www.cdc.gov/vaccines/covid-19/info-by-product/moderna/reactogenicity.html [Consulted: 7 February 2022].

CDC (2021b) Centres for Diseases Control and Prevention (CDC). Reactions and Adverse Events of the Pfizer-BioNTech COVID-19 Vaccine. Available online: https://www.cdc.gov/vaccines/covid-19/info-by-product/pfizer/reactogenicity.html [Consulted: 7 February 2022].

CDC (2021c) Centres for Diseases Control and Prevention (CDC). Multisystem Inflammatory Syndrome (MIS). Atlanta, ga: us department of health and human services. https://www.cdc.gov/mis/index.html [Consulted: 20 March 2022].

Cheng MP, Kozoriz MG, Ahmadi AA, Kelsall J, Paquette K, Onrot JM (2016) Post-vaccination myositis and myocarditis in a previously healthy male. Allergy Asthma Clin Immunol 12: 6. https://doi.org/10.1186/s13223-016-0114-4

Cereda A, Conca C, Barbieri L, Ferrante G, Tumminello G, Lucreziotti S, Guazzi M, Mafrici A (2021) Acute myocarditis after the second dose of SARS-CoV-2 vaccine: Serendipity or atypical causal relationship? Anatol J Cardiol 25(7): 522–523. https://doi.org/10.5152/AnatolJCardiol.2021.99

Crowley A, Ackerman M (2019) Mind the gap: How interspecies variability in igg and its receptors may complicate comparisons of human and non-human primate effector function. Front Immunol 10: 697. https://doi.org/10.3389/fimmu.2019.00697

Deb A, Abdelmalek J, Iwuji K, Nugent K (2021) Acute myocardial injury following COVID-19 vaccination: a case report and review of current evidence from vaccine adverse events reporting system database. J Prim Care Community Health 12: 21501327211029230. https://doi.org/10.1177/21501327211029230

Dekkers G, Bentlage AEH, Stegmann TC, Howie HL, Lissenberg-Thunnissen S, Zimring J, Rispens T, Vidarsson G (2017) Affinity of human IgG subclasses to mouse Fc gamma receptors. MAbs 9(5): 767–773. https://doi.org/10.1080/19420862.2017.1323159  

di Dedda EA, Barison A, Aquaro GD, Ismail TF, Hua A, Mantini C, Ricci F, Pontone G, Volpe A, Secchi F, Di Renzi P, Lovato L, Niro F, Liguori C, De Biase C, Monti L, Cirò A, Marano R, Natale L, Moliterno E, Esposito A, Vignale D, Faletti R, Gatti M, Porcu M, Saba L, Chimenti C, Galea N, Francone M (2022) Cardiac magnetic resonance imaging of myocarditis and pericarditis following COVID-19 vaccination: a multicenter collection of 27 cases. Eur Radiol 32(7): 4352–4360. https://doi.org/10.1007/s00330-022-08566-0

Dickey JB, Albert E, Badr M, Laraja KM, Sena LM, Gerson DS, Saucedo JE, Qureshi W, Aurigemma GP (2021) A series of patients with myocarditis following SARS-CoV-2 vaccination with mRNA-1279 and BNT162b2. JACC: Cardiovasc Imaging 14(9): 1862–1863. https://doi.org/10.1016/j.jcmg.2021.06.003

Dye C, Mills MC (2021) COVID-19 vaccination passports. Science 371(6535): 1184. https://doi.org/10.1126/science.abi5245

Ehrlich P, Klingel K, Ohlmann-Knafo S Hüttinger S, Sood  N, Pickuth D, Kindermann M (2021) Biopsy-proven lymphocytic myocarditis following first mRNA COVID-19 vaccination in a 40-year-old male: case report. Clin Res Cardiol 110(11): 1855–1859. https://doi.org/10.1007/s00392-021-01936-6

Fairweather D, Cooper LT Jr, Blauwet LA (2013) Sex and gender differences in myocarditis and dilated cardiomyopathy. Curr Probl Cardiol 38(1): 7–46. https://doi.org/10.1016/j.cpcardiol.2012.07.003

Feng S, Chiu SS, Chan ELY, Kwan MYW, Wong JSC, Leung CW, Chung Lau Y, Sullivan SG, Malik Peiris JS, Cowling BJ (2018) Effectiveness of influenza vaccination on influenza-associated hospitalizations over time among children in Hong Kong: a test-negative case-control study. Lancet Respir Med 6(12): 925–934. https://doi.org/10.1016/s2213-2600(18)30419-3

Ferdinands JM, Gaglani M, Martin ET, Monto AS, Middleton D, Silveira F, Talbot HK, Zimmerman R, Patel M (2021) Waning vaccine effectiveness against influenza-associated hospitalizations among adults, 2015-2016 to 2018-2019, United States hospitalized adult influenza vaccine effectiveness network. Clin Infect Dis 73(4): 726–729. https://doi.org/10.1093/cid/ciab045

Fischinger S, Boudreau CM, Butler AL, Streeck H, Alter G (2019) Sex differences in vaccine-induced humoral immunity. Semin Immunopathol 41(2): 239–249. https://doi.org/10.1007/s00281-018-0726-5

Frisancho-Kiss S, Coronado MJ, Frisancho JA, Lau VM, Rose NR, Klein SL, Fairweather D (2009) Gonadectomy of male BALB/c mice increases Tim-3(+) alternatively activated M2 macrophages, Tim-3(+) T cells, Th2 cells and Treg in the heart during acute coxsackievirus-induced myocarditis. Brain Behav Immun 23(5): 649–657. https://doi.org/10.1016/j.bbi.2008.12.002

Gargano JW, Wallace M, Hadler SC, Langley G, Su JR, Oster ME, Broder KR, Gee J, Weintraub E, Shimabukuro T, Scobie HM, Moulia D, Markowitz LE, Wharton M, McNally VV, Romero JR, Talbot HK, Lee GM, Daley MF, Oliver SE (2021) Use of mRNA COVID-19 vaccine after reports of myocarditis among vaccine recipients: update from the advisory committee on immunization practices – united states, June 2021. MMWR Morb Mortal Wkly Rep 70(27): 977–982. http://dx.doi.org/10.15585/mmwr.mm7027e2

Guo CW, Alexander M, Dib Y, Lau PKH, Weppler AM, Au-Yeung G, Lee B, Khoo C, Mooney D, Joshi SB, Creati L, Sandhu S (2020) A closer look at immune-mediated myocarditis in the era of combined checkpoint blockade and targeted therapies. Eur J Cancer 124: 15–24. https://doi.org/10.1016/j.ejca.2019.09.009

Gürdoğan M, Yalta K (2020) Myocarditis associated with immune checkpoint inhibitors: Practical considerations in diagnosis and management. Anatol J Cardiol 24(2): 68–75. https://doi.org/10.14744/anatoljcardiol.2020.79584

Hasnie AA, Hasnie UA, Patel N, Aziz MU, Xie M, Lloyd SG, Prabhu SD (2021) Perimyocarditis following first dose of the mRNA-1273 SARS-CoV-2 (Moderna) vaccine in a healthy young male: a case report. BMC Cardiovasc Disord 21: 375. https://doi.org/10.1186/s12872-021-02183-3

Higgins JPT, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, Savović J, Schulz KF, Weeks L, Sterne JAC (2011) The Cochrane collaboration’s tool for assessing risk of bias in randomised trials. BMJ (Online) 343(7829): 1–9. https://doi.org/10.1136/bmj.d5928

Hudson B, Mantooth R, DeLaney M (2021) Myocarditis and pericarditis after vaccination for COVID-19. JACEP Open 2: e12498. https://doi.org/10.1002/emp2.12498

Imazio M, Angelico G, Andriani M, Lobetti-Bodoni L, Davini O, Giustetto C, Rinaldi M (2018) Prevalence and prognostic impact of septal late gadolinium enhancement in acute myocarditis with or without preserved left ventricular function. Am J Cardiol 122(11): 1955–1958. https://doi.org/10.1016/j.amjcard.2018.08.038

Imazio M, Brucato A, Barbieri A, Ferroni F, Maestroni S, Ligabue G, Chinaglia A, Cumetti D, Della Casa G, Bonomi F, Mantovani F, Di Corato P, Lugli R, Faletti R, Leuzzi S, Bonamini R, Modena MG, Belli R (2013) Good prognosis for pericarditis with and without myocardial involvement: Results from a multicenter, prospective cohort study. Circulation 128(1): 42–49. https://doi.org/10.1161/CIRCULATIONAHA.113.001531

Imazio M, Brucato A, Spodick D, Adler Y (2014) Prognosis of myopericarditis as determined from previously published reports. J Cardiovasc Med (Hagerstown) 15: 835–839. https://doi.org/10.2459/jcm.0000000000000082

Jackson N, Kester K, Casimiro D, Gurunathan S, DeRosa F (2020) The promise of mRNA vaccines: A biotech and industrial perspective. NPJ Vaccines 5: 11. https://doi.org/10.1038/s41541-020-0159-8

Jensen S, Thomsen A (2012) Sensing of RNA viruses: a review of innate immune receptors involved in recognizing RNA virus invasion. J Virol 86: 2900–2910. https://doi.org/10.1128/jvi.05738-11

June Choe Y, Yi S, Hwang I, Kim J, Park YJ, Cho E, Jo M, Lee H, Hwa Choi E (2022) Safety and effectiveness of BNT162b2 mRNA COVID-19 vaccine in adolescents. Vaccine 40(5): 691–694. https://doi.org/10.1016/j.vaccine.2021.12.044

Kim HW, Jenista ER, Wendell DC, Azevedo CF, Campbell MJ, Darty SN, Parker MA, Kim RJ (2021) Patients with acute myocarditis following mRNA COVID-19 vaccination. JAMA Cardiol 6(10): 1196–1201. https://doi.org/10.1001/jamacardio.2021.2828

Kim IC, Kim H, Lee HJ, Kim JY, Kim JY (2021) Cardiac imaging of acute myocarditis following COVID-19 mRNA vaccination. J Korean Med Sci 36(32): e229. https://doi.org/10.3346/jkms.2021.36.e229

King WW, Petersen MR, Matar RM, Budweg JB, Cuervo Pardo L, Petersen JW (2021) Myocarditis following mRNA vaccination against SARS-CoV-2, a case series. Am Heart J Plus: Cardiol Res Pract 8: 100042. https://doi.org/10.1016/j.ahjo.2021.100042

Klugar M, Riad A, Mekhemar M, Conrad J, Buchbender M, Howaldt HP, Attia S (2021) Side effects of mRNA-based and viral vector-based COVID-19 vaccines among german healthcare workers. Biology 10(8): 752. https://doi.org/10.3390/biology10080752

Knowlton KU, Knight S, Muhlestein JB, Le VT, Horne BD, May HT, Stenehjem E, Anderson JL (2021) A small but significant increased incidence of acute pericarditis identified after vaccination for SARS-COV-2. Circulation 144(Suppl. 1): A11396. https://doi.org/10.1161/circ.144.suppl_1.11396

Lasrado N, Reddy J (2020) An overview of the immune mechanisms of viral myocarditis. Rev Med Virol 30: e2131. https://doi.org/10.1002/rmv.2131

Lyden D, Olszewski J, Feran M, Job L, Huber S (1987) Coxsackievirus B-3-induced myocarditis. Effect of sex steroids on viremia and infectivity of cardiocytes. Am J Pathol 126: 432–438.

Maron BJ, Udelson JE, Bonow RO, Nishimura RA, Ackerman MJ, Estes NAM, Cooper LT, Link MS, Maron MS (2015) Eligibility and disqualification recommendations for competitive athletes with cardiovascular abnormalities: task force 3: hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy and other cardiomyopathies, and myocarditis. Circulation 132(22): e273–e280. https://doi.org/10.1161/CIR.0000000000000239

Marshall M, Ferguson ID, Lewis P, Jaggi P, Gagliardo C, Collins JS, Shaughnessy R,  Caron R, Fuss C, Corbin KJE, Emuren L, Faherty E, Hall EK, Pentima CD, Oster ME, Paintsil E, Siddiqui S, Timchak DM, Guzman-Cottrill JA (2021) Symptomatic acute myocarditis in 7 adolescents after Pfizer-BioNTech COVID-19 vaccination. Pediatrics 148(3): e2021052478. https://doi.org/10.1542/peds.2021-052478

Matta A, Kunadharaju R, Osman M (2021) Clinical presentation and outcomes of myocarditis post mRNA vaccination: a meta-analysis and systematic review. Cureus 11: e19240. https://doi.org/10.7759/cureus.19240

McLean K, Johnson TJ (2021) Myopericarditis in a previously healthy adolescent male following COVID-19 vaccination: A case report. Acad Emerg Med 28(8): 918–921. https://doi.org/10.1111/acem.14322

Mevorach D, Anis E, Cedar N, Bromberg M, Haas EJ, Nadir E, Olsha-Castell S, Arad D, Hasin T, Levi N, Asleh R, Amir O, Meir K, Cohen D, Dichtiar R, Novick D, Hershkovitz Y, Dagan R, Leitersdorf I, Ben-Ami R, Miskin I, Saliba W, Muhsen K, Levi Y, Green MS, Keinan-Boker L, Alroy-Preis S (2021) Myocarditis after BNT162b2 mRNA vaccine against COVID-19 in Israel. N Engl J Med  385(23): 2140–2149. https://doi.org/10.1056/nejmoa2109730  

Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, Shekelle P, Stewart LA, Group PP (2015) Preferred reporting items for systematic review and meta-analysis protocols (Prisma-p) 2015 statement. Syst Rev 4(1): 1. https://doi.org/doi:10.1186/2046-4053-4-1

Montgomery J, Ryan M, Engler R, Hoffman D, McClenathan B, Collins L, Loran D, Hrncir D, Herring K, Platzer M, Adams N, Sanou A, Cooper LT (2021) Myocarditis following immunization with mRNA COVID-19 vaccines in members of the US military. JAMA Cardiol 6(10): 1202–1206. https://doi.org/10.1001/jamacardio.2021.2833

Nassar M, Nso N, Gonzalez C, Lakhdar S, Alshamam M, Elshafey M, Abdalazeem Y, Nyein A, Punzalan B, Durrance RJ, Alfishawy M, Bakshi S, Rizzo V (2021) COVID-19 vaccine-induced myocarditis: Case report with literature review. Diabetes Metab Syndr 15(5): 102205. https://doi.org/10.1016/j.dsx.2021.102205

Nevet A (2021) Acute myocarditis associated with anti-COVID-19 vaccination. Clin Exp Vaccine Res 10(2): 196–197. https://doi.org/10.7774/cevr.2021.10.2.196

Oster ME, Shay DK, Su JR, Gee J, Creech CB, Broder KR, Edwards K, Soslow JH, Dendy JM, Schlaudecker E, Lang SM, Barnett ED, Ruberg FL, Smith MJ, Campbell MJ, Lopes RD, Sperling LS, Baumblatt JA, Thompson DL, Marquez PL, Strid P, Woo J, Pugsley R, Reagan-Steiner S, DeStefano F, Shimabukuro TT (2022) Myocarditis cases reported after mRNA-based COVID-19 vaccination in the US from December 2020 to august 2021. JAMA 327(4): 331–340. https://doi.org/doi:10.1001/jama.2021.24110

Pardi N, Hogan M, Porter F, Weissman D (2018) mRNA vaccines – a new era in vaccinology. Nat Rev Drug Discov 17: 261–279. https://doi.org/10.1038/nrd.2017.243

Park JW, Lagniton PNP, Liu Y, Xu RH (2021) mRNA vaccines for COVID-19: What, why and how. Int J Biol Sci 17(6): 1446–1460. https://doi.org/10.7150/ijbs.59233

Patel YR, Louis DW, Atalay M. Agarwal S, Shah NR (2021) Cardiovascular magnetic resonance findings in young adult patients with acute myocarditis following mRNA COVID-19 vaccination: a case series. J Cardiovasc Magn Reson 23: 101. https://doi.org/10.1186/s12968-021-00795-4

Patone M, Mei XW, Handunnetthi L, Dixon S, Zaccardi F, Shankar-Hari M, Watkinson P, Khunti K, Harnden A, Coupland CAC, Channon KM, Mills NL, Sheikh A, Hippisley-Cox J (2022) Risks of myocarditis, pericarditis, and cardiac arrhythmias associated with COVID-19  vaccination or SARS-CoV-2 infection. Nat Med 28(2): 410–422. https://doi.org/10.1038/s41591-021-01630-0

Pilishvili T, Fleming-Dutra KE, Farrar JL, Gierke R, Mohr NM, Talan DA, Krishnadasan A, Harland KK, Smithline HA, Hou PC, Lee LC, Lim SC, Moran GJ, Krebs E, Steele M, Beiser DG, Faine B, Haran JP, Nandi U, Schrading WA, Chinnock B, Henning DJ, Vecchio FL, Nadle J, Barter D, Brackney M, Britton A, Marceaux-Galli K, Lim S, Phipps EC, Dumyati G, Pierce R, Markus TM, Anderson DJ, Debes AK, Lin M, Mayer J, Babcock HM, Safdar N, Fischer M, Singleton R, Chea N, Magill SS, Verani J, Schrag S (2021) Interim estimates of vaccine effectiveness of Pfizer-BioNTech and Moderna COVID-19  vaccines among health care personnel – 33 US sites, January-March 2021. MMWR. Morb Mortal Wkly Rep 70(20): 753–758. https://doi.org/10.15585/mmwr.mm7020e2

Potluri T, Fink A, Sylvia K, Dhakal S, Vermillion MS, Steeg LV,  Deshpande S, Narasimhan H, Klein SL (2019) Associated changes in the impact of sex steroids on influenza vaccine responses in males and females. NPJ Vaccines 4: 29. https://doi.org/10.1038/s41541-019-0124-6

Rombey T, Doni K, Hoffmann F, Pieper D, Allers K (2020) More systematic reviews were registered in PROSPERO each year, but few records’ status was up-to-date. J Clin Epidemiol 117: 60–67. https://doi.org/10.1016/j.jclinepi.2019.09.026

Rosner CM, Genovese L, Tehrani BN, Atkins M, Bakhshi H, Chaudhri S, Damluji AA, Lemos JAD, Desai SS, Emaminia A, Flanagan MC, Khera A, Maghsoudi A, Mekonnen G, Muthukumar A, Saeed IM, Sherwood MW, Sinha SS, O’Connor CM, deFilippi CR (2021) Myocarditis temporally associated with COVID-19 vaccination. Circulation 144(6): 502–505. https://doi.org/10.1161/CIRCULATIONAHA.121.055891

Rowland C, Johnson CY (2020) Even finding a COVID-19 vaccine won’t be enough to end the pandemic. Washington Post. May 11, 2020. https://www.washingtonpost.com/business/2020/05/11/coronavirus-vaccine-global-supply/ [Consulted: 1 February 2022].

Ruggieri A, Anticoli S, D’Ambrosio A, Giordani L, Viora M (2016) The influence of sex and gender on immunity, infection and vaccination. Ann Ist Super Sanita 52(2): 198–204. https://doi.org/10.4415/ann_16_02_11

Sahin U, Kariko K, Tureci O (2014) mRNA-based therapeutics–developing a new class of drugs. Nat Rev Drug Discov 13: 759–780. https://doi.org/10.1038/nrd4278

Salah HM, Mehta JL (2021) COVID-19 vaccine and myocarditis. Am J Cardiol 157: 146–148. https://doi.org/10.1016/j.amjcard.2021.07.009

Shaw KE, Cavalcante JL, Han BK, Gössl M (2021) Possible association between COVID-19 vaccine and myocarditis: Clinical and CMR findings. JACC: Cardiovascular Imaging 14(9): 1856–1861. https://doi.org/10.1016/j.jcmg.2021.06.002

Shiyovich A, Witberg G, Aviv Y, Eisen A, Orvin K, Wiessman M, Grinberg T, Porter A, Kornowski R, Hamdan A (2021) Myocarditis following COVID-19 vaccination: magnetic resonance imaging study. Eur Heart J Cardiovasc Imaging 3(8): 1075–1082. https://doi.org/10.1093/ehjci/jeab230

Simone A, Herald J, Chen A, Gulati N, Shen AYJ, Lewin B, Lee MS (2021) Acute myocarditis following COVID-19 mRNA vaccination in adults aged 18 years or  older. JAMA Intern Med 181(12): 1668–1670. https://doi.org/10.1001/jamainternmed.2021.5511

Singh B, Kaur P, Cedeno L, Brahimi T, Patel P, Virk H, Shamoon F, Bikkina M (2021) COVID-10 mRNA vaccine and myocarditis. Eur J Case Rep Intern Med 14;8(7): 002681. https://doi.org/10.12890/2021_002681

Singh VP, Pir MS, Buch T, Kaur A, Kela K, Shah P, Miller J, Naseer R, Ghosh P (2021) Myocarditis linked to Pfizer-Biontech COVID-19 vaccine. Chest 160(4): A444. https://doi.org/10.1016/j.chest.2021.07.437

Snapiri O, Danziger CR, Shirman N, Weissbach A, Lowenthal A, Ayalon I, Adam D, Yarden-Bilavsky H, Bilavsky E (2021) Transient cardiac injury in adolescents receiving the BNT162b2 mRNA COVID-19 vaccine. Pediatr Infect Dis J 40(10): e360–e363. https://doi.org/10.1097/INF.0000000000003235

Starekova J, Bluemke DA, Bradham WS, Grist TM, Schiebler ML, Reeder SB (2021) Myocarditis associated with mRNA COVID-19 vaccination. Radiology 301(2): E409–E411. https://doi.org/10.1148/radiol.2021211430

Sung JG, Sobieszczyk PS, Bhatt DL (2021) Acute myocardial infarction within 24 hours after COVID-19 vaccination. Am J Cardiol 156: 129–131. https://doi.org/10.1016/j.amjcard.2021.06.047

Tenforde M, Olson S, Self W, Network IVY, Investigators H (2021) Effectiveness of Pfizer-BioNTech and Moderna vaccines against COVID-19 among hospitalized adults aged ≥65 years—United States, January–March 2021. Morb Mortal Wkly Rep 70: 674–679. https://doi.org/10.15585/mmwr. mm7018e1

Thevathasan T, Kenny MA, Schreiber F, Fairweather D, Cooper LT, Last J, Krause FJJ, Paul J, Poller WC, Skurk C, Landmesser U, Balzer F, Heidecker B (2021) The strongest sex difference in myocarditis prevalence occurred in young adult patients – A descriptive, multi-center cohort study in 7,031 patients over 22 years. Circulation 144(Suppl. 1): A11548–A11548. https://doi.org/10.1161/circ.144.suppl_1.11548  

Thompson M, Burgess J, Naleway A, Tyner H, Yoon S, Meece J, Olsho L, Caban-Martinez A, Fowlkes A, Lutrick K, Groom H, Dunnigan K, Odean M, Hegmann K, Stefanski E, Edwards L, Schaefer-Solle N, Grant L, Ellingson K, Kuntz J, Zunie T, Thiese M, Ivacic L, Wesley M, Mayo Lamberte J, Sun X, Smith M, Phillips A, Groover K, Yoo Y, Gerald J, Brown R, Herring M, Joseph G, Beitel S, Morrill T, Mak J, Rivers P, Poe B, Lynch B, Zhou Y, Zhang J, Kelleher A, Li Y, Dickerson M, Hanson E, Guenther K, Tong S, Bateman A, Reisdorf E, Barnes J, Azziz-Baumgartner E, Hunt D, Arvay M, Kutty P, Fry A, Gaglani M (2021) Prevention and attenuation of COVID-19 with the BNT162b2 and mRNA-1273 vaccines. N Engl J Med 385: 320–329. https://doi.org/10.1056/NEJMoa2107058  

Trachtenberg BH, Hare JM (2017) Inflammatory cardiomyopathic syndromes. Circ Res 121: 803–818. https://doi.org/10.1161/CIRCRESAHA.117.310221

Trigunaite A, Dimo J, Jørgensen TN (2015) Suppressive effects of androgens on the immune system. Cell Immunol 294(2): 87–94. https://doi.org/10.1016/j.cellimm.2015.02.004

Vaccines and Related Biological Products Advisory Committee Meeting (2020) FDA briefing document: Pfizer-BioNTech COVID-19 Vaccine. New York (NY): Pfizer and BioNTech.

Valbuena-López S, Hinojar R, Puntmann VO (2016) Cardiovascular magnetic resonance in cardiology practice: A concise guide to image acquisition and clinical interpretation. Rev Esp Cardiol 69(2): 202–210. https://doi.org/10.1016/j.rec.2015.11.011

Verma AK, Lavine KJ, Lin CY (2021) Myocarditis after Covid-19 mRNA vaccination. N Engl J Med 385: 1332–1334. https://doi.org/10.1056/NEJMc2109975 

Vollmann D, Eiffert H, Schuster A (2021) Acute perimyocarditis following first dose of mRNA vaccine against COVID-19. Dtsch Arztebl Int 118: 546. https://doi.org/10.3238/arztebl.m2021.0288

WHO (2020a) World Health Organization. Statement on the second meeting of the international health. Regulations (2005) emergency committee regarding the outbreak of novel coronavirus. https://www.who.int/news-room/detail/30-01-2020-st [Consulted: 1 February 2022].

WHO (2020b) World Health Organization. COVID-19 Dashboard. In Available online: https://covid19.who.int/ [Consulted: 7 February 2022].

Witberg G, Barda N, Hoss S, Richter I, Wiessman M, Aviv Y, Grinberg T, Auster O, Dagan N, Balicer RD, Kornowski R (2021) Myocarditis after COVID-19 Vaccination in a Large Health Care Organization. N Engl Med 385: 2132–2139. https://doi.org/10.1056/NEJMoa2110737

Wittrup A, Lieberman J (2015) Knocking down disease: a progress report on siRNA therapeutics. Nat Rev Genet 16(9): 543–552. https://doi.org/10.1038/nrg3978

Woudstra L, Juffermans LJM, Rossum VAC (2018) Infectious myocarditis: The role of the cardiac vasculature. Heart Fail Rev 23: 583–595. https://doi.org/10.1007/s10741-018-9688-x

Yap J, Tham MY, Poh J, Toh D, Chan CL, Lim TW, Lim SL, Chia YW, Lim YT, Choo J, Ding ZP, Foo LL, Kuo S, Lau YH, Lee A, Yeo KK (2022) Pericarditis and myocarditis after COVID-19 mRNA vaccination in a nationwide  setting. Ann Acad Med Singap 51(2): 96–100. https://doi.org/10.47102/annals-acadmedsg.2021425

Zachary M, Edoardo A, Catalin T (2019) The development of software to support multiple systematic review types. Int J Evid Based Healthc 17(1): 36–43. https://doi.org/10.1097/XEB.0000000000000152

Zhang L, Awadalla M, Mahmood SS, Nohria A, Hassan MZO, Thuny F, Zlotoff DA, Murphy SP, Stone JR, Golden DLA, Alvi RM, Rokicki A, Jones-O’Connor M, Cohen JV, Heinzerling LM, Mulligan C, Armanious M, Barac A, Forrestal BJ, Sullivan RJ, Kwong RY, Yang EH, Damrongwatanasuk R, Chen CL, Gupta D, Kirchberger MC, Moslehi JJ, Coelho-Filho OR, Ganatra S, Rizvi MA, Sahni G, Tocchetti CG, Mercurio V, Mahmoudi M, Lawrence DP, Reynolds KL, Weinsaft JW, Baksi AJ, Ederhy S, Groarke JD, Lyon AR, Fradley MG, Thavendiranathan P, Neilan TG (2020b) Cardiovascular magnetic resonance in immune checkpoint inhibitor-associated myocarditis. Eur Heart J 41(18): 1733–1743. https://doi.org/10.1093/eurheartj/ehaa051

Zhang NN, Li XF, Deng YQ, Zhao H, Huang YJ, Yang G, Huang WJ, Gao P, Zhou C, Zhang RR, Guo Y, Sun SH, Fan H, Zu SL, Chen Q, He Q, Cao TS, Huang XY, Qiu HY, Nie JH, Jiang Y, Yan HY, Ye Q, Zhong X, Xue XL, Zha ZY, Zhou D, Yang X, Wang, YC, Ying B, Qi CF (2020a) A thermostable mRNA vaccine against COVID-19. Cell 182(5): 1271–1283.e16. https://doi.org/10.1016/j.cell.2020.07.024

© 2023 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Oxidative stress in COVID-19 infection

J. Pharm. Pharmacogn. Res., vol. 11, no. 1, pp. 63-75, January-February 2023.

DOI: https://doi.org/10.56499/jppres22.1535_11.1.63

Original Article

Oxidative stress in diverse clinical conditions of SARS-CoV-2 Cuban hospitalized patients

[Estrés oxidativo en diferentes condiciones clínicas de pacientes cubanos hospitalizados con SARS-CoV-2]

Lizette Gil-del Valle1*, Rosario Gravier-Hernández1, Mario M. Delgado-Guerra2, Joniel A. Sánchez-Márquez2, Olga E. López-Fernández2, Miguel A. Acosta-Suárez1, Teresa Rosell-Guerra1, Rodolfo Suárez-Iznaga3, Raiza Martínez-Casanueva3, Zullyt Zamora-Rodriguez4, Lidia A. Fernández-García4, Yusimit Bermudez-Alfonso1, María C. Hernández-Gonzalez-Abreu1, Gabino Garrido5**

1Institute “Pedro Kourí” (IPK), Havana, Cuba.

2Hospital Ernesto Guevara, University of Informatics’ Science, Havana, Cuba.

3Hospital Salvador Allende, Havana, Cuba.

4National Center of Scientific Research, BioCubaFarma, Havana, Cuba.

5Departamento de Ciencias Farmacéuticas, Facultad de Ciencias, Universidad Católica del Norte, Antofagasta, Chile.

*E-mail: *lgil@ipk.sld.cu, **gabino.garrido@ucn.cl

Abstract

Context: COVID-19 related to SARS-CoV-2 infection generates inflammation with increased reactive oxygen species production. Drug treatment and others factors could influence systemic oxidative stress during pathogenic insult.

Aims: To determine the redox status in COVID-19 patients with different clinical conditions and explore the relationship between redox and hematological hemochemical variables.

Methods: In this comparative longitudinal study, blood samples were drawn from 160 individuals divided into four groups: COVID-19 asymptomatic, COVID-19 symptomatic (low and moderate symptoms), COVID-19 convalescent, and presumable healthy subjects. Demographic, redox, hematological, and hemochemical indices were assessed. Statistical analyses compared the median values of each variable and explored individual, simultaneous indices, and multivariate alteration.

Results: Relative to the healthy group, acute COVID-19, and convalescent groups had significant differences in global damage indices and antioxidant status (p<0.05). The convalescent group showed significantly higher damage (malondialdehyde, advanced oxidation protein products, nitric oxide) and lower antioxidant enzymatic activities and glutathione concentration compared to other groups (p<0.05). Global modification of redox indices showed that more than 80% of studied individuals in acute conditions had simultaneous detrimental differences compared to a healthy status. The discriminant analysis permitted obtaining two canonical functions (p< 0.05) that reflect 98% of redox variables with 95% of variances with successful case classifications.

Conclusions: These results corroborate that oxidative stress occurred in different COVID-19 and post-acute conditions with different molecular alterations of redox indices. Redox diagnosis should be considered in early diagnosis and treatment of infection, which would be worthwhile to conduct a more comprehensive study and management of disease evolution.

Keywords: antioxidant status; COVID-19; oxidative stress; oxidative damage; SARS-CoV-2.

Resumen

Contexto: El COVID-19 relacionado con la infección por SARS-CoV-2 genera inflamación con aumento de la producción de especies reactivas del oxígeno. El tratamiento farmacológico y otros factores podrían influir en el estrés oxidativo sistémico durante el insulto patogénico.

Objetivos: Determinar el estado redox en pacientes con COVID-19 con diferentes condiciones clínicas y explorar la relación entre las variables redox y hemoquímicas.

Métodos: En este estudio longitudinal comparativo, se extrajeron muestras de sangre de 160 individuos divididos en cuatro grupos: COVID-19 asintomáticos, COVID-19 sintomáticos (síntomas bajos y moderados), COVID-19 convalecientes y sujetos presuntamente sanos. Se evaluaron los índices demográficos, redox, hematológicos y hemoquímicos. Los análisis estadísticos compararon los valores medios de cada variable y exploraron las alteraciones en los índices individuales, simultáneos y multivariadas.

Resultados: En relación con el grupo sano, los grupos COVID-19 agudo y convaleciente presentaron diferencias significativas en los índices de daño global y en el estado antioxidante (p<0,05). El grupo convaleciente mostró un daño significativamente mayor (malondialdehído, productos proteicos de oxidación avanzada, óxido nítrico) y menores actividades enzimáticas antioxidantes y concentración de glutatión en comparación con los otros grupos (p<0,05). La modificación global de los índices redox mostró que más del 80% de los individuos estudiados tenían diferencias perjudiciales simultáneas en comparación con el estado saludable. El análisis discriminante permitió obtener dos funciones canónicas (p< 0,05) que reflejan el 98% de las variables redox con el 95% de las varianzas con clasificaciones de casos acertadas.

Conclusiones: Estos resultados corroboran que el estrés oxidativo se presentó en diferentes COVID-19 y condiciones post-agudas con diferentes alteraciones moleculares de los índices redox. El diagnóstico redox debe ser considerado en el diagnóstico y tratamiento precoz de la infección, lo que valdría la pena para realizar un estudio y manejo más exhaustivo de la evolución de la enfermedad.

Palabras Clave: daño oxidativo; COVID-19; estado antioxidante; estrés oxidativo; SARS-CoV-2.

Citation Format: Gil-del Valle L, Gravier-Hernández R, Delgado-Guerra MM, Sánchez-Márquez JA, López-Fernández OE, Acosta-Suárez MA, Rosell-Guerra T, Suárez-Iznaga R, Martínez-Casanueva R, Zamora-Rodriguez Z, Fernández-García LA, Bermudez-Alfonso Y, Hernández-Gonzalez-Abreu MC, Garrido G (2023) Oxidative stress in diverse clinical conditions of SARS-CoV-2 Cuban hospitalized patients. J Pharm Pharmacogn Res 11(1): 63–75. https://doi.org/10.56499/jppres22.1535_11.1.63
References

Ahmed SM, Luo L, Namani A, Wang XJ, Tang X (2017) Nrf2 signaling pathway: Pivotal roles in inflammation. Biochim Biophys Acta Mol Basis Dis 1863(2): 585–597. https://doi.org/10.1016/j.bbadis.2016.11.005

Amatore D, Sgarbanti R, Aquilano K, Baldelli S, Limongi D, Civitelli L, Nencioni L, Garaci E, Ciriolo MR, Palamara AT (2015) Influenza virus replication in lung epithelial cells depends on redox-sensitive pathways activated by NOX4-derived ROS. Cell Microbiol 17(1): 131–45. https://doi.org/10.1111/cmi.12343

Azkur AK, Akdis M, Azkur D, Sokolowska M, van de Veen W, Brüggen MC, O’Mahony L, Gao Y, Nadeau K, Akdis CA (2020) Immune response to SARS-CoV-2 and mechanisms of immunopathological changes in COVID-19. Allergy 75(7): 1564–1581. https://doi.org/10.1111/all.14364

Ballatori N, Krance SM, Notenboom S, Shi S, Tieu K, Hammond CL (2009) Glutathione dysregulation and the etiology and progression of human diseases. Biol Chem 390(3): 191–214. https://doi.org/10.1515/BC.2009.033

Bhaskar S, Sinha A, Banach M, Mittoo S, Weissert R, Kass JS, Rajagopal S, Pai AR, Kutty S (2020) Cytokine storm in COVID-19-immunopathological mechanisms, clinical considerations, and therapeutic approaches: The REPROGRAM Consortium position paper. Front Immunol 11: 1648. https://doi.org/10.3389/fimmu.2020.01648

Cecchini R, Cecchini AL (2020) SARS-CoV-2 infection pathogenesis is related to oxidative stress as a response to aggression. Med Hypotheses 143: 110102. https://doi.org/10.1016/j.mehy.2020.110102

Ceriello A, Testa R (2009) Antioxidant anti-inflammatory treatment in type 2 diabetes. Diabetes Care 32 Suppl 2(Suppl 2): S232–S236. https://doi.org/10.2337/dc09-S316

Channappanavar R, Perlman S (2017) Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Semin Immunopathol 39(5): 529–539. https://doi.org/10.1007/s00281-017-0629-x

Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Xia J, Yu T, Zhang X, Zhang L (2020a) Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 395(10223): 507–513. https://doi.org/10.1016/S0140-6736(20)30211-7

Chen R, Sang L, Jiang M, Yang Z, Jia N, Fu W, Xie J, Guan W, Liang W, Ni Z, Hu Y, Liu L, Shan H, Lei C, Peng Y, Wei L, Liu Y, Hu Y, Peng P, Wang J, Liu J, Chen Z, Li G, Zheng Z, Qiu S, Luo J, Ye C, Zhu S, Zheng J, Zhang N, Li Y, He J, Li J, Li S, Zhong N; Medical Treatment Expert Group for COVID-19 (2020b) Longitudinal hematologic and immunologic variations associated with the progression of COVID-19 patients in China. J Allergy Clin Immunol 146(1): 89–100. https://doi.org/10.1016/j.jaci.2020.05.003

Chiscano-Camón L, Ruiz-Rodriguez JC, Ruiz-Sanmartin A, Roca O, Ferrer R (2020) Vitamin C levels in patients with SARS-CoV-2-associated acute respiratory distress syndrome. Crit Care 24(1): 522. https://doi.org/10.1186/s13054-020-03249-y

Clairborne A (1986) Catalase activity. In: Green-Wald R, editor. Handbook of Methods for Oxygen Radical Research. Boca Ratón: CRC Press, p. 283–284.

Conti P, Ronconi G, Caraffa A, Gallenga CE, Ross R, Frydas I, Kritas SK (2020) Induction of pro-inflammatory cytokines (IL-1 and IL-6) and lung inflammation by Coronavirus-19 (COVI-19 or SARS-CoV-2): anti-inflammatory strategies. J Biol Regul Homeost Agents 34(2): 327–331. https://doi.org/10.23812/CONTI-E

Dasgupta A, Kalhan A, Kalra S (2020) Long term complications and rehabilitation of COVID-19 patients. J Pak Med Assoc 70(Suppl 3)(5): S131-S135. https://doi.org/10.5455/JPMA.32

Deavall DG, Martin EA, Horner JM, Roberts R (2012) Drug-induced oxidative stress and toxicity. J Toxicol 2012: 645460. https://doi.org/10.1155/2012/645460

Delgado-Roche L, Mesta F (2020) Oxidative stress as key player in severe acute respiratory syndrome coronavirus (SARS-CoV) infection. Arch Med Res 51(5): 384–387. https://doi.org/10.1016/j.arcmed.2020.04.019

Di Meo S, Reed TT, Venditti P, Victor VM (2016) Role of ROS and RNS sources in physiological and pathological conditions. Oxid Med Cell Longev 2016: 1245049. https://doi.org/10.1155/2016/1245049

Dosch SF, Mahajan SD, Collins AR (2009) SARS coronavirus spike protein-induced innate immune response occurs via activation of the NF-kappaB pathway in human monocyte macrophages in vitro. Virus Res 142(1-2): 19–27. https://doi.org/10.1016/j.virusres.2009.01.005

Dysangco A, Liu Z, Stein JH, Dubé MP, Gupta SK (2017) HIV infection, antiretroviral therapy, and measures of endothelial function, inflammation, metabolism, and oxidative stress. PLoS One 12(8): e0183511. https://doi.org/10.1371/journal.pone.0183511

Erdelmeier I, Gérard-Monnier D, Yadan JC, Chaudière J (1998) Reactions of N-methyl-2-phenylindole with malondialdehyde and 4-hydroxyalkenals. Mechanistic aspects of the colorimetric assay of lipid peroxidation. Chem Res Toxicol 11(10): 1184–1194. https://doi.org/10.1021/tx970180z

Fakhri S, Nouri Z, Moradi SZ, Farzaei MH (2020) Astaxanthin, COVID-19 and immune response: Focus on oxidative stress, apoptosis and autophagy. Phytother Res 34(11): 2790–2792. https://doi.org/10.1002/ptr.6797

Fang FC (2011) Antimicrobial actions of reactive oxygen species. mBio 2(5): e00141–11. https://doi.org/10.1128/mBio.00141-11

Gadotti AC, Lipinski AL, Vasconcellos FT, Marqueze LF, Cunha EB, Campos AC, Oliveira CF, Amaral AN, Baena CP, Telles JP, Tuon FF, Pinho RA (2021) Susceptibility of the patients infected with Sars-Cov2 to oxidative stress and possible interplay with severity of the disease. Free Radic Biol Med 165: 184–190. https://doi.org/10.1016/j.freeradbiomed.2021.01.044

Gemelli Against COVID-19 Post-Acute Care Study Group (2020) Post-COVID-19 global health strategies: the need for an interdisciplinary approach. Aging Clin Exp Res 32(8): 1613–1620. https://doi.org/10.1007/s40520-020-01616-x

Goud PT, Bai D, Abu-Soud HM (2021) A multiple-hit hypothesis involving reactive oxygen species and myeloperoxidase explains clinical deterioration and fatality in COVID-19. Int J Biol Sci 17(1): 62–72. https://doi.org/10.7150/ijbs.51811

Granger DL, Taintor RR, Boockvar KS, Hibbs JB, Jr. (1996) Measurement of nitrate and nitrite in biological samples using nitrate reductase and Griess reaction. Methods Enzymol 268: 142-151. https://doi.org/10.1016/s0076-6879(96)68016-1

Greenhalgh T, Knight M, A’Court C, Buxton M, Husain L (2020) Management of post-acute covid-19 in primary care. BMJ 370: m3026. https://doi.org/10.1136/bmj.m3026

Ifrim DC, Quintin J, Joosten LA, Jacobs C, Jansen T, Jacobs L, Gow NA, Williams DL, van der Meer JW, Netea MG (2014) Trained immunity or tolerance: opposing functional programs induced in human monocytes after engagement of various pattern recognition receptors. Clin Vaccine Immunol 21(4): 534–545. https://doi.org/10.1128/CVI.00688-13

Imai Y, Kuba K, Neely GG, Yaghubian-Malhami R, Perkmann T, van Loo G, Ermolaeva M, Veldhuizen R, Leung YH, Wang H, Liu H, Sun Y, Pasparakis M, Kopf M, Mech C, Bavari S, Peiris JS, Slutsky AS, Akira S, Hultqvist M, Holmdahl R, Nicholls J, Jiang C, Binder CJ, Penninger JM (2008) Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury. Cell 133(2): 235–249. https://doi.org/10.1016/j.cell.2008.02.043

Kalem AK, Kayaaslan B, Neselioglu S, Eser F, Hasanoglu İ, Aypak A, Akinci E, Akca HN, Erel O, Guner R (2021) A useful and sensitive marker in the prediction of COVID-19 and disease severity: Thiol. Free Radic Biol Med 166: 11–17. https://doi.org/10.1016/j.freeradbiomed.2021.02.009

Kemp HI, Corner E, Colvin LA (2020) Chronic pain after COVID-19: implications for rehabilitation. Br J Anaesth 125(4): 436–440. https://doi.org/10.1016/j.bja.2020.05.021

Khomich OA, Kochetkov SN, Bartosch B, Ivanov AV (2018) Redox biology of respiratory viral infections. Viruses 10(8): 392. https://doi.org/10.3390/v10080392

Kobayashi EH, Suzuki T, Funayama R, Nagashima T, Hayashi M, Sekine H, Tanaka N, Moriguchi T, Motohashi H, Nakayama K, Yamamoto M (2016) Nrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription. Nat Commun 7: 11624. https://doi.org/10.1038/ncomms11624

Kosanovic T, Sagic D, Djukic V, Pljesa-Ercegovac M, Savic-Radojevic A, Bukumiric Z, Lalosevic M, Djordjevic M, Coric V, Simic T (2021) Time course of redox biomarkers in COVID-19 pneumonia: Relation with inflammatory, multiorgan impairment biomarkers and CT findings. Antioxidants (Basel) 10(7): 1126. https://doi.org/10.3390/antiox10071126

Lee C (2018) Therapeutic modulation of virus-induced oxidative stress via the Nrf2-dependent antioxidative pathway. Oxid Med Cell Longev 2018: 6208067. https://doi.org/10.1155/2018/6208067

Liguori I, Russo G, Curcio F, Bulli G, Aran L, Della-Morte D, Gargiulo G, Testa G, Cacciatore F, Bonaduce D, Abete P (2018) Oxidative stress, aging, and diseases. Clin Interv Aging 13: 757–772. https://doi.org/10.2147/CIA.S158513

Liu C, Zhou Q, Li Y, Garner LV, Watkins SP, Carter LJ, Smoot J, Gregg AC, Daniels AD, Jervey S, Albaiu D (2020) Research and development on therapeutic agents and vaccines for COVID-19 and related human coronavirus diseases. ACS Cent Sci 6(3): 315–331. https://doi.org/10.1021/acscentsci.0c00272

Majewska E, Kasielski M, Luczynski R, Bartosz G, Bialasiewicz P, Nowak D (2004) Elevated exhalation of hydrogen peroxide and thiobarbituric acid reactive substances in patients with community acquired pneumonia. Respir Med 98(7): 669–676. https://doi.org/10.1016/j.rmed.2003.08.015

Mao C, Yuan JQ, Lv YB, Gao X, Yin ZX, Kraus VB, Luo JS, Chei CL, Matchar DB, Zeng Y, Shi XM (2019) Associations between superoxide dismutase, malondialdehyde and all-cause mortality in older adults: a community-based cohort study. BMC Geriatr 19(1): 104. https://doi.org/10.1186/s12877-019-1109-z

Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47(3): 469–474. https://doi.org/10.1111/j.1432-1033.1974.tb03714.x

Marrocco I, Altieri F, Peluso I (2017) Measurement and clinical significance of biomarkers of oxidative stress in humans. Oxid Med Cell Longev 2017: 6501046. https://doi.org/10.1155/2017/6501046

Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB (2014) Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal 20(7): 1126–1167. https://doi.org/10.1089/ars.2012.5149

Muhammad Y, Kani YA, Iliya S, Muhammad JB, Binji A, El-Fulaty Ahmad A, Kabir MB, Umar Bindawa K, Ahmed A (2021) Deficiency of antioxidants and increased oxidative stress in COVID-19 patients: A cross-sectional comparative study in Jigawa, Northwestern Nigeria. SAGE Open Med 9: 2050312121991246. https://doi.org/10.1177/2050312121991246

Muralidharan S, Mandrekar P (2013) Cellular stress response and innate immune signaling: integrating pathways in host defense and inflammation. J Leukoc Biol 94(6): 1167–1184. https://doi.org/10.1189/jlb.0313153

Palipoch S, Koomhin P (2015) Oxidative stress-associated pathology: A review. Sains Malays 44(10): 1441–1451.

Patlevič P, Vašková J, Švorc P, Jr., Vaško L, Švorc P (2016) Reactive oxygen species and antioxidant defense in human gastrointestinal diseases. Integr Med Res 5(4): 250–258. https://doi.org/10.1016/j.imr.2016.07.004

Phaniendra A, Jestadi DB, Periyasamy L (2015) Free radicals: properties, sources, targets, and their implication in various diseases. Indian J Clin Biochem 30(1): 11–26. https://doi.org/10.1007/s12291-014-0446-0

Pickering AM, Vojtovich L, Tower J, A Davies KJ (2013) Oxidative stress adaptation with acute, chronic, and repeated stress. Free Radic Biol Med 55: 109–118. https://doi.org/10.1016/j.freeradbiomed.2012.11.001

Pincemail J, Cavalier E, Charlier C, Cheramy-Bien JP, Brevers E, Courtois A, Fadeur M, Meziane S, Goff CL, Misset B, Albert A, Defraigne JO, Rousseau AF (2021) Oxidative stress status in COVID-19 patients hospitalized in intensive care unit for severe pneumonia. A pilot study. Antioxidants (Basel) 10(2): 257. https://doi.org/10.3390/antiox10020257

Pisoschi AM, Pop A (2015) The role of antioxidants in the chemistry of oxidative stress: A review. Eur J Med Chem 97: 55–74. https://doi.org/10.1016/j.ejmech.2015.04.040

Polonikov A (2020) Endogenous deficiency of glutathione as the most likely cause of serious manifestations and death in COVID-19 patients. ACS Infect Dis 6(7): 1558–1562. https://doi.org/10.1021/acsinfecdis.0c00288

Schaefer L (2014) Complexity of danger: the diverse nature of damage-associated molecular patterns. J Biol Chem 289(51): 35237–35245. https://doi.org/10.1074/jbc.R114.619304

Schieber M, Chandel NS (2014) ROS function in redox signaling and oxidative stress. Curr Biol 24(10): R453–R462. https://doi.org/10.1016/j.cub.2014.03.034

Sebastiano M, Chastel O, de Thoisy B, Eens M, Costantini D (2016) Oxidative stress favours herpes virus infection in vertebrates: a meta-analysis. Curr Zool 62(4): 325–332. https://doi.org/10.1093/cz/zow019

Sies H, Berndt C, Jones DP (2017) Oxidative stress. Annu Rev Biochem 86: 715–748. https://doi.org/10.1146/annurev-biochem-061516-045037

Sies H, Jones DP (2020) Reactive oxygen species (ROS) as pleiotropic physiological signalling agents. Nat Rev Mol Cell Biol 21(7): 363–383. https://doi.org/10.1038/s41580-020-0230-3

Tay MZ, Poh CM, Rénia L, MacAry PA, Ng LFP (2020) The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol 20(6): 363–374. https://doi.org/10.1038/s41577-020-0311-8

Vlahos R, Stambas J, Bozinovski S, Broughton BR, Drummond GR, Selemidis S (2011) Inhibition of Nox2 oxidase activity ameliorates influenza A virus-induced lung inflammation. PLoS Pathog 7(2): e1001271. https://doi.org/10.1371/journal.ppat.1001271

WHO (2020) Coronavirus disease (COVID-2019) situation reports 2020 [cited 13/7/2022][Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports

Witko-Sarsat V, Friedlander M, Nguyen Khoa T, Capeillère-Blandin C, Nguyen AT, Canteloup S, Dayer JM, Jungers P, Drüeke T, Descamps-Latscha B (1998) Advanced oxidation protein products as novel mediators of inflammation and monocyte activation in chronic renal failure. J Immunol 161(5): 2524–2532.

Xuan Y, Gào X, Anusruti A, Holleczek B, Jansen E, Muhlack DC, Brenner H, Schöttker B (2019) Association of serum markers of oxidative stress with incident major cardiovascular events, cancer incidence, and all-cause mortality in type 2 diabetes patients: Pooled results from two cohort studies. Diabetes Care 42(8): 1436–1445. https://doi.org/10.2337/dc19-0292

Ye Q, Wang B, Mao J (2020) The pathogenesis and treatment of the `Cytokine Storm’ in COVID-19. J Infect 80(6): 607–613. https://doi.org/10.1016/j.jinf.2020.03.037

Zhou P, Yang X-L, Wang X-G, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL, Chen HD, Chen J, Luo Y, Guo H, Jiang RD, Liu MQ, Chen Y, Shen XR, Wang X, Zheng XS, Zhao K, Chen QJ, Deng F, Liu LL, Yan B, Zhan FX, Wang YY, Xiao GF, Shi ZL (2020) A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579(7798): 270–273. https://doi.org/10.1038/s41586-020-2012-7

© 2023 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Role of ACE and IL-6 levels on CKD prognosis

J. Pharm. Pharmacogn. Res., vol. 11, no. 1, pp. 55-62, January-February 2023.

DOI: https://doi.org/10.56499/jppres22.1518_11.1.55

Original Article

The role of plasma angiotensin-converting enzyme and interleukin-6 levels on the prognosis of non-dialysis chronic kidney disease patients

[Papel de los niveles plasmáticos de la enzima convertidora de angiotensina e interleucina-6 en el pronóstico de los pacientes con enfermedad renal crónica no sometidos a diálisis]

Hendri Susilo1,2**, Mochammad Thaha3,4, Budi Susetyo Pikir1,2, Mochamad Yusuf Alsagaff1,2, Satriyo Dwi Suryantoro3,4, Ifan Ali Wafa5, Nando Reza Pratama5, David Setyo Budi5, Bayu Satria Wiratama6, Citrawati Dyah Kencono Wungu7,8*

1Department of Cardiology and Vascular Medicine, Universitas Airlangga Hospital, Surabaya, Indonesia.

2Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.

3Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.

4Department of Internal Medicine, Universitas Airlangga Hospital, Surabaya, Indonesia.

5Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.

6Departement of Biostatistics and Epidemiology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Indonesia.

7Department of Physiology and Medical Biochemistry, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia.

8Institute of Tropical Disease, Universitas Airlangga, Surabaya.

E-mail: *citrawati.dyah@fk.unair.ac.id; **hendrisusilo@staf.unair.ac.id

Abstract

Context: Inflammatory factors and oxidative stress were discovered to play significant roles in the progression of chronic kidney disease (CKD). There is, however, no research on the direct impact of high plasma angiotensin converting enzyme (ACE) and interleukin (IL)-6 levels on CKD prognosis, particularly in non-hemodialysis patients.

Aims: To investigate the potential role of plasma ACE and IL-6 levels in CKD prognosis.

Methods: A total of 75 non-dialysis CKD patients participated in this cross-sectional study. The estimated glomerular filtration rate (e-GFR) and albuminuria were used to determine the prognosis of CKD. The plasma ACE and IL-6 levels were measured using an enzyme-linked immunoassay (ELISA). Spearman’s rank correlational analysis was used to examine the relationship between ACE and IL-6 plasma levels with the prognosis of CKD.

Results: The result showed a statistically significant correlation between age and plasma ACE (p = 0.038, r = 0.241), serum creatinine, and urine albumin-creatinine ratio with CKD prognosis (p<0.0001). A negative significant correlation was found between the e-GFR and CKD prognosis (p<0.0001). Additionally, there were also significant correlations between plasma ACE and IL-6 with CKD prognosis (p = 0.021, r = 0.266 and p = 0.04, r = 0.238, respectively). A significant positive correlation was also found between plasma ACE and IL-6 (p = 0.024, r = 0.260).

Conclusions: There was a significant correlation between plasma ACE and IL-6 levels with CKD prognosis. Further investigation revealed a statistically significant positive relationship between plasma ACE and IL-6 levels.

Keywords: angiotensin converting enzyme; chronic kidney disease; interleukin-6; non-hemodialysis; prognosis.

Resumen

Contexto: Se ha descubierto que los factores inflamatorios y el estrés oxidativo desempeñan un papel importante en la progresión de la enfermedad renal crónica (ERC). Sin embargo, no existen investigaciones sobre la repercusión directa de los niveles elevados de la enzima convertidora de angiotensina (ECA) e interleucina (IL)-6 en plasma sobre el pronóstico de la ERC, en particular en los pacientes que no están en hemodiálisis.

Objetivos: Investigar el papel potencial de los niveles plasmáticos de ECA e IL-6 en el pronóstico de la ERC.

Métodos: Un total de 75 pacientes con ERC no en diálisis participaron en este estudio transversal. Se utilizaron la tasa de filtración glomerular estimada (TFGe) y la albuminuria para determinar el pronóstico de la ERC. Los niveles plasmáticos de ECA e IL-6 se midieron mediante un inmunoensayo enzimático (ELISA). Se utilizó el análisis correlacional por rangos de Spearman para examinar la relación entre los niveles plasmáticos de ECA e IL-6 y el pronóstico de la ERC.

Resultados: El resultado mostró una correlación estadísticamente significativa entre la edad y la ECA plasmática (p = 0,038, r = 0,241), la creatinina sérica y el cociente albúmina-creatinina en orina con el pronóstico de la ERC (p<0,0001). Se encontró una correlación negativa significativa entre el e-GFR y el pronóstico de la ERC (p<0,0001). Además, también hubo correlaciones significativas entre la ECA y la IL-6 plasmáticas con el pronóstico de la ERC (p = 0,021, r = 0,266 y p = 0,04, r = 0,238, respectivamente). También se halló una correlación positiva significativa entre la ECA plasmática y la IL-6 (p = 0,024, r = 0,260).

Conclusiones: Existe una correlación significativa entre los niveles plasmáticos de ECA e IL-6 con el pronóstico de la ERC. Investigaciones posteriores revelaron una relación positiva estadísticamente significativa entre los niveles plasmáticos de ECA e IL-6.

Palabras Clave: enfermedad renal crónica; enzima convertidora de angiotensina; interleucina-6; no hemodiálisis; pronóstico.

Citation Format: Susilo H, Thaha M, Pikir BS, Alsagaff MY, Suryantoro SD, Wafa IA, Pratama NR, Budi DS, Wiratama BS, Wungu CDK (2023) The role of plasma angiotensin-converting enzyme and interleukin-6 levels on the prognosis of non-dialysis chronic kidney disease patients. J Pharm Pharmacogn Res 11(1): 55–62. https://doi.org/10.56499/jppres22.1518_11.1.55
References

Amador-Martínez I, Pérez-Villalva R, Uribe N, Cortés-González C, Bobadilla NA, Barrera-Chimal J (2019) Reduced endothelial nitric oxide synthase activation contributes to cardiovascular injury during chronic kidney disease progression. Am J Physiol Renal Physiol 317: F275–F285. https://doi.org/10.1152/AJPRENAL.00020.2019

Anguiano L, Riera M, Pascual J, Valdivielso JM, Barrios C, Betriu A, Mojal S, Fernández E, Soler MJ, Faura A, Castro E, María V, Molí T, Soria M, Aladrén RMJ, Almirall J, Ponz E, Arteaga CJ, Bajo RMA, Belart RM, Bielsa-García S, Bover SJ, Bronsoms AJ, Cabezuelo RJB, Muray CS, Calviño VJ, Caro AP, Carreras BJ, Cases AA, Massó JE, Castilla PJ, Cigarrán GS, López PS, Comas ML, Comerma I, Compte JMT, Cuberes IM, De ÁF, Hevia OC, De ADLFG, Del PPMD, Diaz-Tejeiro IR, Dotori M, Duarte V, Estupiñan TS, Fernández RMJ, Fernández RML, Fernández G, Galán SA, García CC, García HAL, García MM, Gil SL, Aguilar M, Górriz JL, Huarte LE, Lerma JL, Liebana CA, Marín ÁJP, Martín AN, Martín GJ, Martínez CA, Martínez VM, Martínez I, Moina EI, Moreno LHS, Mouzo MR, Munar VA, Muñoz DAB, Navarro GJF, Nieto J, Carreño A, Novoa FE, Ortiz A, Fernandez B, Paraíso V, Pérez FM, Peris DA, Piñera HC, Prados GMD, Prieto VM, Puig MC, Rivera GM, Rubio E, Ruiz P, Salgueira LM, Martínez PAI, Sánchez TJA, Sánchez JE, Sans LR, Saracho R, Sarrias M, Prat O, Sousa F, Toran D, Tornero MF, Usón CJJ, Valera CI, Vilaprinyo DPMM, Virto RRC (2015) Circulating angiotensin-converting enzyme 2 activity in patients with chronic kidney disease without previous history of cardiovascular disease. Nephrol Dial Transplant 30: 1176–1185. https://doi.org/10.1093/NDT/GFV025

Bikbov B, Purcell C, Levey A, Smith M, Abdoli A, Abebe M, Adebayo O, Afarideh M, Agarwal S (2020) Global, regional, and national burden of chronic kidney disease, 1990 – 2017 : A systematic analysis for the Global Burden of Disease Study 2017. Lancet 395: 709–733. https://doi.org/10.1016/S0140-6736(20)30045-3

Carrero JJ, Stenvinkel P (2010) Inflammation in end-stage renal disease–what have we learned in 10 years? Semin Dial 23: 498–509. https://doi.org/10.1111/J.1525-139X.2010.00784.X

Chang HL, Wu CC, Lee SP, Chen YK, Su W, Su SL (2019) A predictive model for progression of CKD. Medicine (Baltimore) 98: e16186. https://doi.org/10.1097/MD.0000000000016186

Chen TK, Knicely DH, Grams ME (2019) Chronic kidney disease diagnosis and management. JAMA 322: 1294. https://doi.org/10.1001/jama.2019.14745

Christofides EA, Desai N (2021) Optimal early diagnosis and monitoring of diabetic kidney disease in type 2 diabetes mellitus: Addressing the barriers to albuminuria testing. J Prim Care Community Health 12. https://doi.org/10.1177/21501327211003683

Dai S, Ding M, Liang N, Li Z, Li D, Guan L, Liu H (2019) Associations of ACE I/D polymorphism with the levels of ACE, kallikrein, angiotensin II and interleukin-6 in STEMI patients. Sci Rep 9: 19719. https://doi.org/10.1038/s41598-019-56263-8

Duni A, Liakopoulos V, Roumeliotis S, Peschos D, Dounousi E (2019) Oxidative stress in the pathogenesis and evolution of chronic kidney disease: Untangling Ariadne’s thread. Int J Mol Sci 20: 3711. https://doi.org/10.3390/IJMS20153711

Imig JD, Ryan MJ (2013) Immune and inflammatory role in renal disease. Compr Physiol 3: 957–976. https://doi.org/10.1002/CPHY.C120028

International Society of Nephrology (2013) Summary of recommendation statements. Kidney Int Suppl 3: P5–14. https://doi.org/10.1038/kisup.2012.77

Kagami S (2012) Involvement of glomerular renin-angiotensin system (RAS) activation in the development and progression of glomerular injury. Clin Exp Nephrol 16: 214–220. https://doi.org/10.1007/S10157-011-0568-0

Kamińska J, Stopiński M, Mucha K, Jędrzejczak A, Gołębiowski M, Niewczas MA, Pączek L, Foroncewicz B (2019) IL 6 but not TNF is linked to coronary artery calcification in patients with chronic kidney disease. Cytokine 120: 9–14. https://doi.org/10.1016/J.CYTO.2019.04.002

Khosla N, Kalaitzidis R, Bakris GL (2009) The kidney, hypertension, and remaining challenges. Med Clin North Am 93: 697–715. https://doi.org/10.1016/J.MCNA.2009.02.001

Krata N, Zagożdżon R, Foroncewicz B, Mucha K (2018) Oxidative stress in kidney diseases: The cause or the consequence? Arch Immunol Ther Exp (Warsz). 66: 211–220. https://doi.org/10.1007/S00005-017-0496-0

Lambers HHJ, Gansevoort RT, Brenner BM, Cooper ME, Parving HH, Shahinfar S, De ZD (2010) Comparison of different measures of urinary protein excretion for prediction of renal events. J Am Soc Nephrol 21: 1355–1360. https://doi.org/10.1681/ASN.2010010063

Lee DE, Qamar M, Wilke RA (2021) Relative contribution of genetic and environmental factors in CKD. S D Med 74: 306–309.

Lee DL, Sturgis LC, Labazi H, Osborne JB, Fleming C, Pollock JS, Manhiani M, Imig JD, Brands MW (2006) Angiotensin II hypertension is attenuated in interleukin-6 knockout mice. Am J Physiol Heart Circ Physiol 290: H935–H940. https://doi.org/10.1152/AJPHEART.00708.2005

Levin A, Stevens PE, Bilous RW, Coresh J, De FALM, De JPE, Griffith KE, Hemmelgarn BR, Iseki K, Lamb, EJ, Levey AS, Riella MC, Shlipak MG, Wang H, White CT, Winearls CG (2013) Kidney disease: Improving global outcomes (KDIGO) CKD work group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 3: P1–150. https://doi.org/10.1038/kisup.2012.73

Luther JM, Gainer JV, Murphey LJ, Yu C, Vaughan DE, Morrow JD, Brown NJ (2006) Angiotensin II induces interleukin-6 in humans through a mineralocorticoid receptor-dependent mechanism. Hypertension 48: 1050–1057. https://doi.org/10.1161/01.HYP.0000248135.97380.76

Magno AL, Herat LY, Carnagarin R, Schlaich MP, Matthews VB (2019) Current knowledge of IL-6 cytokine family members in acute and chronic kidney disease. Biomedicines 7: 19. https://doi.org/10.3390/BIOMEDICINES7010019

Miller WG, Bruns DE, Hortin GL, Sandberg S, Aakre KM, McQueen MJ, Itoh Y, Lieske JC, Seccombe DW, Jones G, Bunk DM, Curhan GC, Narva AS (2009) Current issues in measurement and reporting of urinary albumin excretion. Clin Chem 55: 24–38. https://doi.org/10.1373/CLINCHEM.2008.106567

Miura H, Nakayama M, Sato T (1984) Serum angiotensin converting enzyme (S-ACE) activity in patients with chronic renal failure on regular hemodialysis. Jpn Heart J 25: 87–92. https://doi.org/10.1536/IHJ.25.87

Oberg BP, McMenamin E, Lucas FL, McMonagle E, Morrow J, Ikizler TA, Himmelfarb J (2004) Increased prevalence of oxidant stress and inflammation in patients with moderate to severe chronic kidney disease. Kidney Int 65: 1009–1016. https://doi.org/10.1111/J.1523-1755.2004.00465.X

Perna A, Ruggenenti P, Testa A, Spoto B, Benini R, Misefari V, Remuzzi G, Zoccali C (2000) ACE genotype and ACE inhibitors induced renoprotection in chronic proteinuric nephropathies1. Kidney Int 57: 274–281. https://doi.org/10.1046/J.1523-1755.2000.00818.X

Rodríguez-Ortiz ME, Pontillo C, Rodríguez M, Zürbig P, Mischak H, Ortiz A (2018) Novel urinary biomarkers for improved prediction of progressive EGFR loss in early chronic kidney disease stages and in high risk individuals without chronic kidney disease. Sci Rep 8: 15940. https://doi.org/10.1038/S41598-018-34386-8

Roy N, Rosas SE (2021) IL-6 is associated with progression of coronary artery calcification and mortality in incident dialysis patients. Am J Nephrol 52: 745–752. https://doi.org/10.1159/000518652

Shi C, Lu K, Xia H, Zhang P, Zhang B (2020) Alteration and association between serum ACE2/ angiotensin(1-7)/Mas axis and oxidative stress in chronic kidney disease: A pilot study. Medicine (Baltimore). 99: E21492. https://doi.org/10.1097/MD.0000000000021492

Soler MJ, Riera M, Crespo M, Mir M, Márquez E, Pascual MJ, Puig JM, Pascual J (2012) Circulating angiotensin-converting enzyme 2 activity in kidney transplantation: a longitudinal pilot study. Nephron Clin Pract 121: c144–c150. https://doi.org/10.1159/000345508

Su H, Lei CT, Zhang C (2017) Interleukin-6 signaling pathway and its role in kidney disease: An update. Front Immunol 8: 405. https://doi.org/10.3389/fimmu.2017.00405

Susilo H, Pikir BS, Thaha M, Alsagaff MY, Suryantoro SD, Wungu CDK, Wafa IA, Pakpahan C, Oceandy D (2022) The effect of angiotensin converting enzyme (ACE) I/D polymorphism on atherosclerotic cardiovascular disease and cardiovascular mortality risk in non-hemodialyzed chronic kidney disease: The mediating role of plasma ace level. Genes (Basel) 13: 1121. https://doi.org/10.3390/genes13071121

Tang WH, Hung WC, Wang CP, Wu CC, Hsuan CF, Yu TH, Hsu CC, Cheng YA, Chung FM, Lee YJ, Lu YC (2022) The lower limit of reference of urinary albumin/creatinine ratio and the risk of chronic kidney disease progression in patients with type 2 diabetes mellitus. Front Endocrinol (Lausanne) 13: 858267. https://doi.org/10.3389/FENDO.2022.858267

Vaidya SR, Aeddula NR (2022) Chronic Renal Failure. In: StatPearls. Treasure Island (FL): StatPearls Publishing.

Yan MT, Chao CT, Lin SH (2021) Chronic Kidney Disease: Strategies to Retard Progression. Int J Mol Sci 22. https://doi.org/10.3390/IJMS221810084

Yang CW, Lu LC, Chang CC, Cho CC, Hsieh WY, Tsai CH, Lin YC, Lin CS (2017) Imbalanced plasma ACE and ACE2 level in the uremic patients with cardiovascular diseases and its change during a single hemodialysis session. Ren Fail 39: 719–728. https://doi.org/10.1080/0886022X.2017.1398665

Zhang W, Wang W, Yu H, Zhang Y, Dai Y, Ning C, Tao L, Sun H, Kellems RE, Blackburn MR, Xia Y (2012) Interleukin 6 underlies angiotensin II-induced hypertension and chronic renal damage. Hypertension 59: 136–144. https://doi.org/10.1161/HYPERTENSIONAHA.111.173328

Zhong J, Yang HC, Fogo AB (2017) A perspective on chronic kidney disease progression. Am J Physiol Renal Physiol 312: F375–F384. https://doi.org/10.1152/AJPRENAL.00266.2016

© 2023 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Effect of rhamnetin on HMG-CoA reductase and LDLR expression

J. Pharm. Pharmacogn. Res., vol. 11, no. 1, pp. 47-54, January-February 2023.

DOI: https://doi.org/10.56499/jppres22.1507_11.1.47

Original Article

Rhamnetin decreases the expression of HMG-CoA reductase gene and increases LDL receptor in HepG2 cells

[Ramnetina disminuye la expresión del gen de la HMG-CoA reductasa y aumenta los receptores de LDL en las células HepG2]

Raghad R. Al-Yousef1, Manal M. Abbas1,2, Razan Obeidat2, Manal A. Abbas1,2*

1Faculty of Allied Medical Sciences, Al-Ahliyya Amman University, Amman 19328, Jordan.

2Pharmacological and Diagnostic Research Center, Al-Ahliyya Amman University, Amman 19328, Jordan.

*E-mail: m.abbas@ammanu.edu.jo

Abstract

Context: Rhamnetin is a naturally occurring methylated derivative of quercetin. This flavonoid is abundant in Syzygium aromaticum, Coriandrum sativum Prunus cerasus, and Rhamnus spp.

Aims: To evaluate the effects of rhamnetin on HMG-CoA reductase and low-density lipoprotein receptor (LDLR) gene and protein expressions in the HepG2 hepatoma cell line.

Methods: The expression of HMG-CoA reductase and LDLR genes and proteins were studied in HepG2 liver cancer cell line by PCR, Western blot, and indirect ELISA, as well as their antioxidant activity.

Results: Rhamnetin was non-toxic up to 200 μM on HepG2 at 24, 48, and 72 h. Rhamnetin (25 µM) upregulated LDLR gene expression by 1.66 folds compared to 3.12 folds exerted by the well-known hypocholesterolemic drug simvastatin. Rhamnetin (100 µM) increased the expression of LDLR protein at the cell membrane, while the other concentrations produced no significant change from the control (vehicle-treated). In HepG2 cell lysate, LDLR was increased by 50 µM of rhamnetin. Also, rhamnetin increased SOD activity significantly by 100.98, 86.28, and 100.98% by the concentrations 25, 50, and 100 µM, respectively. Using the same concentrations, rhamnetin reduced H2O2 levels by 50, 67, and 76.34%, respectively.

Conclusions: This study demonstrated for the first time that rhamnetin reduced HMG-CoA reductase gene expression and increased LDLR in HepG2 cells.

Keywords: HepG2; hydroxymethylglutaryl CoA reductase; LDL; rhamnetin; receptors.

Resumen

Contexto: La ramnetina es un derivado metilado natural de la quercetina. Este flavonoide abunda en las especies Syzygium aromaticum, Coriandrum sativum, Prunus cerasus y Rhamnus spp.

Objetivos: Evaluar los efectos de la ramnetina en las expresiones génicas y proteicas de la HMG-CoA reductasa y el receptor de la lipoproteína de baja densidad (LDLR) en la línea celular de hepatoma HepG2.

Métodos: Se estudió la expresión de los genes y proteínas de la HMG-CoA reductasa y del LDLR en la línea celular de hepatoma HepG2 mediante PCR, Western blot y ELISA indirecto, así como su actividad antioxidante.

Resultados: La ramnetina fue no tóxica hasta 200 μM en HepG2 a las 24, 48 y 72 h. La ramnetina (25 µM) aumentó la expresión del gen LDLR en 1,66 veces en comparación con 3,12 veces ejercida por el conocido fármaco hipocolesterolemiante simvastatina. La ramnetina (100 µM) aumentó la expresión de la proteína LDLR en la membrana celular, mientras que las demás concentraciones no produjeron cambios significativos con respecto al control (tratado con vehículo). En el lisado de células HepG2, el LDLR aumentó con 50 µM de ramnetina. Asimismo, la ramnetina aumentó significativamente la actividad de la SOD en 100,98; 86,28 y 100,98% mediante las concentraciones de 25, 50 y 100 µM, respectivamente. Utilizando las mismas concentraciones, la ramnetina redujo los niveles de H2O2 en 50, 67 y 76,34%, respectivamente.

Conclusiones: Este estudio demostró por primera vez que la ramnetina redujo la expresión del gen de la HMG-CoA reductasa y aumentó el LDLR en células HepG2.

Palabras Clave: HepG2; hidroximetilglutaril CoA reductasa; LDL; ramnetina; receptores.

Citation Format: Al-Yousef RR, Abbas MM, Obeidat R, Abbas MA (2023) Rhamnetin decreases the expression of HMG-CoA reductase gene and increases LDL receptors in HepG2 cells. J Pharm Pharmacogn Res 11(1): 47–54. https://doi.org/10.56499/jppres22.1507_11.1.47
References

Abbas MM, Kandil Yİ, Abbas MA (2020) R-(-)-carvone attenuated doxorubicin induced cardiotoxicity in vivo and potentiated its anticancer toxicity in vitro. Balkan Med J 37: 98–103. https://doi.org/10.4274/balkanmedj.galenos.2019.2019.7.117

Brown MS, Goldstein JL (1986) A receptor-mediated pathway for cholesterol homeostasis. Science 232: 34–47. https://doi.org/10.1126/science.3513311

Chaudhry N, Tariq P (2006) Bactericidal activity of black pepper, bay leaf, aniseed and coriander against oral isolates. Pak J Pharm Sci 19: 214-218.

Cuoco G, Mathe C, Vieillescazes C (2014) Liquid chromatographic analysis of flavonol compounds in green fruits of three Rhamnus species used in Stil de grain. Microchem J 115: 130-137. https://doi.org/10.1016/j.microc.2014.03.006

Goldstein JL, Brown MS (1990) Regulation of the mevalonate pathway. Nature 343: 425-430. https://doi.org/10.1038/343425a0

Grundy SM (2005) The issue of statin safety: where do we stand? Circulation 111: 3016-3019. https://doi.org/10.1161/CIRCULATIONAHA.105.557652

Hansson GK (2001) Immune mechanisms in atherosclerosis. Arterioscler Thromb Vasc Biol 21: 1876-1890. https://doi.org/10.1161/hq1201.100220

Igarashi K, Ohmuma M (1995) Effects of isorhamnetin, rhamnetin, and quercetin on the concentrations of cholesterol and lipoperoxide in the serum and liver and on the blood and liver antioxidative enzyme activities of rats. Biosci Biotechnol Biochem 59: 595-601. https://doi.org/10.1271/bbb.59.595

Jiang H, Zhan W, Liu X,  Jiang S (2008) Antioxidant activities of extracts and flavonoid compounds from Oxytropis falcate Bunge. Nat Prod Res 22: 1650-1656. https://doi.org/10.1080/14786410701875686

Jnawali HN, Lee E, Jeong K-W, Shin A, Heo Y-S, Kim Y (2014) Anti-inflammatory activity of rhamnetin and a model of its binding to c-Jun NH2-terminal kinase 1 and p38 MAPK. J Natl Prod 77: 258-263. https://doi.org/10.1021/np400803n

Khan MA, Hashim MJ, Mustafa H, Baniyas MY, Al Suwaidi SKBM, AlKatheeri R, Alblooshi FM, Almatrooshi ME, Alzaabi ME, Al Darmaki RS, Lootah SN (2020) Global epidemiology of ischemic heart disease: Results from the global burden of disease study. Cureus 12(7): e9349. https://doi.org/10.7759/cureus.9349

Kotseva K, Stagmo M, De Bacquer D, De Backer G, Wood D, Group EIS (2008) Treatment potential for cholesterol management in patients with coronary heart disease in 15 European countries: findings from the EUROASPIRE II survey. Atherosclerosis 197: P710-717. https://doi.org/10.1016/j.atherosclerosis.2007.07.004

Lee H, Kim HJ, Chae H, Yoon NE, Jung BH (2021) Aster glehni F. Schmidt extract modulates the activities of HMG-CoA reductase and fatty acid synthase. Plants 10: 2287. https://doi.org/10.3390/plants10112287

Lee KP, Kim J-E, Park W-H (2015) Cytoprotective effect of rhamnetin on miconazole-induced H9c2 cell damage. Nutr Res Pract 9: 586-591. https://doi.org/10.4162/nrp.2015.9.6.586

Mahdavi A, Bagherniya M, Fakheran O, Reiner Ž, Xu S, Sahebkar A (2020) Medicinal plants and bioactive natural compounds as inhibitors of HMG‐CoA reductase: A literature review. BioFactors 46: 906-926. https://doi.org/10.1002/biof.1684

Mayne J, Dewpura T, Raymond A, Cousins M, Chaplin A, Lahey KA, LaHaye SA, Mbikay M, Ooi TC, Chrétien M (2008) Plasma PCSK9 levels are significantly modified by statins and fibrates in humans. Lipids in health and disease 7(1): 22. https://doi.org/10.1186/1476-511X-7-22

Mattarei A, Biasutto L, Rastrelli F, Garbisa S, Marotta E, Zoratti M, Paradisi C (2010) Regioselective O-derivatization of quercetin via ester intermediates. An improved synthesis of rhamnetin and development of a new mitochondriotropic derivative. Molecules 15: 4722-4736. https://doi.org/10.3390/molecules15074722

Morikawa S, Umetani M, Nakagawa S, Yamazaki H, Suganami H, Inoue K, Kitahara M, Hamakubo T, Kodama T, Saito Y (2000) Relative induction of mRNA for HMG CoA reductase and LDL receptor by five different HMG-CoA reductase inhibitors in cultured human cells. J Atheroscler Thromb 7(3): 138-144. https://doi.org/10.5551/jat1994.7.138

Nawrocki JW, Weiss SR, Davidson MH, Sprecher DL, Schwartz SL, Lupien P-J, Jones PH, Haber HE, Black DM (1995) Reduction of LDL cholesterol by 25% to 60% in patients with primary hypercholesterolemia by atorvastatin, a new HMG-CoA reductase inhibitor. Arterioscler Thromb Vasc Biol 15: 678-682. https://doi.org/10.1161/01.atv.15.5.678

Nimkuntod P, Tongdee P (2015) Plasma low-density lipoprotein cholesterol/high-density lipoprotein cholesterol concentration ratio and early marker of carotid artery atherosclerosis. J Med Assoc Thai 98: S58-63.

Novo Belchor M, Hessel Gaeta H, Fabri Bittencourt Rodrigues C, Ramos da Cruz Costa C, de Oliveira Toyama D, Domingues Passero LF, Dalastra Laurenti M, Hikari Toyama M (2017) Evaluation of rhamnetin as an inhibitor of the pharmacological effect of secretory phospholipase A2. Molecules 22: 1441. https://doi.org/10.3390/molecules22091441

Park E-S, Kang JC, Jang YC, Park JS, Jang SY, Kim D-E, Kim B, Shin HS (2014) Cardioprotective effects of rhamnetin in H9c2 cardiomyoblast cells under H2O2-induced apoptosis. J Ethnopharmacol 153: 552-560. https://doi.org/10.1016/j.jep.2014.02.019

Reiner Ž (2010) Combined therapy in the treatment of dyslipidemia. Fundam Clin Pharmacol 24: 19-28. https://doi.org/10.1111/j.1472-8206.2009.00764.x

Reiner Ž, De Bacquer D, Kotseva K, Prugger C, De Backer G, Wood D, EUROASPIRE III study group (2013) Treatment potential for dyslipidaemia management in patients with coronary heart disease across Europe: findings from the EUROASPIRE III survey. Atherosclerosis 231: P300-307. https://doi.org/10.1016/j.atherosclerosis.2013.09.020

Szabo ME, Gallyas E, Bak I, Rakotovao A, Boucher F, de Leiris J, Nagy N, Varga E, Tosaki A (2004) Heme oxygenase-1–related carbon monoxide and flavonoids in ischemic/reperfused rat retina. Invest Ophthalmol Vis Sci 45: 3727-3732. https://doi.org/10.1167/iovs.03-1324

Tacherfiout M, Petrov PD, Mattonai M, Ribechini E, Ribot J, Bonet ML, Khettal B (2018) Antihyperlipidemic effect of a Rhamnus alaternus leaf extract in Triton-induced hyperlipidemic rats and human HepG2 cells. Biomed Pharmacother 101: 501-509. https://doi.org/10.1016/j.biopha.2018.02.106

Vogel RA (2012) PCSK9 inhibition: the next statin? Am Coll Cardiol 59: 2354-2355. https://doi.org/10.1016/j.jacc.2012.03.011

Vosgen B,  Herrmann K (1980) Flavonol glycosides of pepper (Piper nigrum), clove (Syzygium aromaticum) and allspice (Pimenta dioica). 3. Phenolics of spices. Z Lebensm Unters Forch 170: 204-207. https://doi.org/10.1007/BF01042541

Yang H-X, Zhang M, Long S-Y, Tuo Q-H, Tian Y, Chen J-X, Zhang CP, Liao DF (2020) Cholesterol in LDL receptor recycling and degradation. Clin Chim Acta 500: 81-86. https://doi.org/10.1016/j.cca.2019.09.022

© 2023 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Photoprotective compounds from Baccharis papillosa

J. Pharm. Pharmacogn. Res., vol. 11, no. 1, pp. 33-46, January-February 2023.

DOI: https://doi.org/10.56499/jppres22.1477_11.1.33

Original Article

Quantification and in vitro photo-protective studies of phenolic compounds from Baccharis papillosa Rusby

[Cuantificación y estudios de fotoprotección in vitro de compuestos fenólicos de Baccharis papillosa Rusby]

Alberto Calle1#, Cecilia K. Curi-Borda1#, Cervando Gutiérrez1,2, Lily Salcedo1, Yonny Flores1, Giovanna R. Almanza1*

1Laboratorio de Bioorgánica, Instituto de Investigaciones Químicas (IIQ), Facultad de Ciencias Puras y Naturales, Universidad Mayor de San Andrés, Calle Andrés Bello y Calle 27 Cota Cota, Edificio FCPN, 4º Piso, La Paz- Bolivia.

2Instituto de Investigaciones Fármaco Bioquímicas (IIFB), Facultad de Ciencias Farmaceúticas y Bioquímicas, Universidad Mayor de San Andrés, Av. Saavedra 222, Miraflores, La Paz-Bolivia.

#Authors contributed equally to the present study.

*E-mail: galmanza@fcpn.edu.bo

Abstract

Context: The ethanolic extract of the leaves from Baccharis papillosa, a plant used in Bolivian folk medicine, presents high UVB/UVA absorption spectrum, and therefore, it could have photo-protective potential.

Aims: To isolate, identify and quantify the compounds of an enriched extract in phenolic compounds obtained from the ethanolic extract of Baccharis papillosa in different seasons and geographical altitudes, and evaluate its photo-protective potential.

Methods: The enriched extract in phenolic compounds was submitted to phytochemical analysis for compound isolation. The enriched extract and isolated compounds were identified by NMR, and monitored by HPLC and spectroscopic methods. The enriched extract with photo-protective potential was analyzed to determine its Spectroscopic Sun Protection Factor (SSPF), its Broad Spectrum Index (BSI) and its photo-protective activity on Escherichia coli bacteria.

Results: Six flavonoids and two cinnamic acid derivatives were isolated and identified. Four of them are reported in B. papillosa for the first time in this study. The highest concentration of total flavonoids was observed in spring and at the highest altitude. The major compound, drupanin, was the main responsible of the high UVB (290-320 nm) absorption spectrum. The high presence of flavonoids in the extract explains the absorption spectrum in the UVA (320-400 nm) region.

Conclusions: The phenolic compounds enriched extract has photo-protective properties comparable to standard commercial synthetic sunscreens and presents an attractive BSI.

Keywords: Broad Spectrum Index (BSI); cinnamic acid derivative; flavonoids; photo-protective activity; Spectroscopic Sun Protection Factor (SSPF).

Resumen

Contexto: El extracto etanólico de las hojas de Baccharis papillosa, planta utilizada en la medicina popular boliviana, presenta un alto espectro de absorción UVB/UVA por lo que podría presentar potencial fotoprotector.

Objetivos: Aislar, identificar y cuantificar los compuestos de un extracto enriquecido en compuestos fenólicos obtenido a partir del extracto etanólico de Baccharis papillosa en diferentes épocas del año y altitudes geográficas y evaluar su potencial fotoprotector.

Métodos: El extracto enriquecido en compuestos fenólicos fue sometido a análisis fitoquímicos para aislamiento de compuestos. El extracto enriquecido y los compuestos aislados fueron identificados por RMN, y monitoreados por HPLC y métodos espectroscópicos. El potencial fotoprotector del extracto enriquecido se analizó mediante la determinación de su Factor de Protección Solar Espectroscópico (SSPF), su Índice de Amplio Espectro (BSR) y su actividad fotoprotectora sobre bacterias Escherichia coli.

Resultados: Se aislaron e identificaron seis flavonoides y dos derivados del ácido cinámico, de los cuales, cuatro de ellos se reportan en este estudio por primera vez en esta especie. La mayor concentración de flavonoides totales se observó en primavera y a mayor altura. El compuesto mayoritario, drupanina, fue el principal responsable del alto espectro de absorción UVB (290-320 nm) del extracto enriquecido. La alta presencia de flavonoides en el extracto explica el espectro de absorción en la región UVA (320-400 nm).

Conclusiones: El extracto enriquecido en compuestos fenólicos tiene propiedades fotoprotectoras comparables a filtros solares sintéticos comerciales estándar y presenta un amplio espectro de protección solar.

Palabras Clave: derivado del ácido cinámico; factor de protección solar espectroscópico; flavonoides; fotoprotección; índice de amplio espectro.

Citation Format: Calle A, Curi-Borda CK, Gutierrez C, Salcedo L, Flores Y, Almanza GR (2023) Quantification and in vitro photo-protective studies of phenolic compounds from Baccharis papillosa Rusby. J Pharm Pharmacogn Res 11(1): 33–46. https://doi.org/10.56499/jppres22.1477_11.1.33
References

Almanza G, Arduz C, Balderrama L, Ocaña L, Flores E (2000) Estudio fitoquímico de Baccharis leptophylla, biodirigido contra Neurospora crassa. Rev Bol Quim 17: 1-8.

Almeida WA, d. S. Sousa LRD, dos Santos A, de Azevedo AS, do Nascimento AM, Amparo TR, Bianco de Souza GH, Henrique dos Santos OD, Leão Andrade  Â, Cazati T, de Abreu Vieira PM, Pires Bueno PC, Rebello dos Santos VM (2020) Green propolis: In vitro photoprotective and photostability studies of single and incorporated extracts in a sunscreen formulation. Rev Bras Farmacogn 30: 436-443. https://doi.org/10.1007/s43450-020-00071-z

Andersen OM, Markham KR (2005) Flavonoids: Chemistry, biochemistry and applications: CRC Press, pp. 1256.

Calderón H (2001) Fotoprotección, bases y aplicación. Rev Chil Reumatol 17: 54-58.

Calle A, San Martín Á, Melgarejo M, Flores Y, Almanza G (2017) Evaluation of flavonoid contents and antibacterial activity of five Bolivian Baccharis species. Rev Bol Quím 34: 112-122.

Calle A, Yupanqui J, Flores Y, Almanza GR (2012) Flavonoides de Baccharis boliviensis. Rev Bol Quím 29: 158-163.

Camacho F (2001) Antiguos y nuevos aspectos de la fotoprotección. Rev Int Dermatol Dermocosmét Clín 4: 441-448.

CAS Common Chemistry (2021) CAS, a division of the American Chemical Society, n.d. Quercetin 3,4′-dimethyl ether. Retrieved from https://commonchemistry.cas.org/detail?cas_rn=33429-83-3 [Consulted July, 2022]

Catalogue No. TM50-TM60 (2002) McFarland Standard, for in vitro use only. Dalynn, Biologicals. http://www.dalynn.com/dyn/ck_assets/files/tech/TM53.pdf [Consulted July, 2022]

ChemSpider CSID:600426 (2021) trans-caffeic acid. Retrieved from http://www.chemspider.com/Chemical-Structure.600426.html [Consulted July, 2022]

Cornard J-P, Lapouge C (2006) Absorption spectra of caffeic acid, caffeate and their 1: 1 complex with Al (III): density functional theory and time-dependent density functional theory investigations. J Phys Chem 110: 7159-7166. https://doi.org/10.1021/jp060147y

da Silva Fernandes A, Alencar AS, Evangelista H, Mazzei JL, Felzenszwalb I (2015) Photoprotective and toxicological activities of extracts from the Antarctic moss Sanionia uncinata. Pharmacogn Mag 11: 38-43. https://doi.org/10.4103/0973-1296.149701

da Silva VV, Ropke CD, de Almeida RL, Miranda DV, Kera CZ, Rivelli DP, Sawada TCH, Barros SBM (2005) Chemical stability and SPF determination of Pothomorphe umbellata extract gel and photostability of 4-nerolidylcathecol. Int J Pharm 303: 125-131. https://doi.org/10.1016/j.ijpharm.2005.07.006

Diffey BL (1994) A method for broad spectrum classification of sunscreens. Int J Cosmet Sci 16: 47-52. https://doi.org/10.1111/j.1467-2494.1994.tb00082.x

Enríquez S, Quispe RE, Amurrio P, Peñaranda JC, Calle A, Orsag V, Almanza GR (2018) Flavonoid contents in leaves of Baccharis latifolia, according to the type of leaf, and its dependence on the physicochemical properties of soils. Rev Bol Quím 35: 146-154.

Escobar Z, Flores Y, Tejeda L, Alvarado JA, Sterner O, Almanza GR (2009) Phenolic compounds from Baccharis papillosa subsp. papillosa. Rev Bol Quím 26: 111-117.

Fleming DP (2008) Quantification of the environmental solar ultraviolet radiation field at the human eye and the investigation of peripherally focused rays. (Ph.D. thesis) Technological University Dublin, Dublin, Ireland. https://doi.org/10.21427/D7XG6P

Gajardo S, Aguilar M, Stowhas T, Salas F, Lopez J, Quispe C, Buc-Calderon P, Benites J (2016) Determination of sun protection factor and antioxidant properties of six Chilean Altiplano plants. Bol Latinoam Caribe Plant Med Aromat15: 352-363.

Garcia Forero A, Villamizar Mantilla DA, Núñez LA, Ocazionez RE, Stashenko EE, Fuentes JL (2019) Photoprotective and antigenotoxic effects of the flavonoids apigenin, naringenin and pinocembrin. Photochem Photobiol 95: 1010-1018. https://doi.org/10.1111/php.13085

Gene RM, Cartañá C, Adzet T, Marin E, Parella T, Canigueral S (1996) Anti-inflammatory and analgesic activity of Baccharis trimera: Identification of its active constituents. Planta Med 62: 232-235. https://doi.org/10.1055/s-2006-957866

Grotewold E (2006) The science of flavonoids. Columbus, Ohio: Springer. https://doi.org/10.1007/978-0-387-28822-2

Körner C (2007) The use of ‘altitude’ in ecological research. Trends Ecol Evol 22: 569-574. https://doi.org/10.1016/j.tree.2007.09.006

Landry LG, Chapple CC, Last RL (1995) Arabidopsis mutants lacking phenolic sunscreens exhibit enhanced ultraviolet-B injury and oxidative damage. Plant Physiol 109: 1159-1166. https://doi.org/10.1104/pp.109.4.1159

Lavola A (1998) Accumulation of flavonoids and related compounds in birch induced by UV-B irradiance. Tree Physiol 18: 53-58. https://doi.org/10.1093/treephys/18.1.53

Li J, Ou-Lee T-M, Raba R, Amundson RG, Last RL (1993) Arabidopsis flavonoid mutants are hypersensitive to UV-B irradiation. Plant Cell 5: 171-179. https://doi.org/10.1105/tpc.5.2.171

Lim H, Draelos Z (2009) Clinical guide to sunscreens and photoprotection. New York: Informa Healthcare USA, pp. 320.

Loza Almanza R, Neri Guarachi L, López Gavincha Y, Mamani Mamani M, Arias Miranda JL, Almanza Vega G, Gonzales Dávalos E, Bermejo Benito P (2011) Evaluación de la toxicidad de los extractos etanólicos de Baccharis latifolia y Baccharis papillosa en animales de experimentación. Biofarbo 19: 22-27.

Mansur J, Rodrigues M, D’ascenção M, Azulay R (1986a) Correlação entre a determinação do fator de proteção solar em seres humanos e por espectrofotometria. An Bras Dermatol 61(4): 167-172.

Mansur J, Rodrigues M, D’ascenção M, Azulay R (1986b) Determinação do fator de proteção solar por espectrofotometria. An Bras Dermatol 61(3): 121-124.

Mazza CA, Zavala J, Scopel, AL, Ballaré CL (1999) Perception of solar UVB radiation by phytophagous insects: behavioral responses and ecosystem implications. Proc Natl Acad Sci USA 96: 980-985. https://doi.org/10.1073/pnas.96.3.980

Monschein M, Jaindl K, Buzimkić S, Bucar F (2015) Content of phenolic compounds in wild populations of Epilobium angustifolium growing at different altitudes. Pharm Biol 53: 1576-1582. https://doi.org/10.3109/13880209.2014.993039

Moreno MI, Moreno LH (2010) Fotoprotección. Rev Asoc Colomb Dermatol 18: 31-39.

Muela A, Garcia-Bringas J, Arana I, Barcina I (2000) The effect of simulated solar radiation on Escherichia coli: the relative roles of UV-B, UV-A, and photosynthetically active radiation. Microb Ecol 39: 65-71. https://doi.org/10.1007/s002489900181

Nichols JA, Katiyar SK (2010) Skin photoprotection by natural polyphenols: anti-inflammatory, antioxidant and DNA repair mechanisms. Arch Dermatol Res 302: 71-83. https://doi.org/10.1007/s00403-009-1001-3

Nole G, Johnson AW (2004) An analysis of cumulative lifetime solar ultraviolet radiation exposure and the benefits of daily sun protection. Dermatol Ther 17: 57-62. https://doi.org/10.1111/j.1396-0296.2004.04S1007.x

Peñaranda JC, Rodrigo G, Ticona-Bustillos A, Valenzuela E, Ramos S, San Martin A, Ghezzi F, Almanza GR (2020) Variation in concentration of flavonoids and chlorophyll, and changes on morphology and foliar anatomy, due to visible (PAR) or ultraviolet (UVA, UVB) radiation in Baccharis latifolia. Rev Bol Quim 37: 210-222. http://doi.org/10.34098/2078-3949.37.5.1

Pérez MT (2012) Fotoprotección: 15 consejos para un broceado seguro. Farm Prof 26: 46-50.

Rengifo-Penadillos R (2013) Cuantificación de flavonoides en el extracto etanólico de propóleos. Pharmaciencia 1: 51-56.

Ribeiro RP (2004) Desenvolvimento e validação da metodologia de análise do teor de filtros solares e determinação do FPS in vitro em formulações fotoprotetoras comerciais. PhD Thesis, UFRJ, Rio de Janeiro, Brasil.

Rigel DS, Berson DS, Ceilley RI, Cole CA, Draelos ZD (2006) Photoprotection: Recent advances in sunscreen stability. Skin and Allergy News (suppl.): 4-11.

Rodrigo GC, Almanza GR, Akesson B, Duan R-D (2010) Antiproliferative activity of extracts of some Bolivian medicinal plants. J Med Plant Res 4: 2204-2210.

Salcedo Ortiz L, Flores Y, Sterner O, Almanza Vega GR (2013) ent-kaurane diterpenoids from Baccharis leptophylla Rev Bol de Quím 30: 60-65.

Sánchez-Saldaña L, Lanchipa P, Pancorbo J, Regis A, Sánchez E (2002) Fotoprotectores tópicos. Dermatol Peru 12(2): 156-163.

Silva-Carvalho R, Baltazar F, Almeida-Aguiar C (2015) Propolis: A complex natural product with a plethora of biological activities that can be explored for drug development. Evid Based Complement Alternat Med 2015: 206439. https://doi.org/10.1155/2015/206439

Sotillo WS, Tarqui S, Huang X, Almanza G, Oredsson S (2021) Breast cancer cell line toxicity of a flavonoid isolated from Baccharis densiflora. BMC Complement Med Ther 21: 188. https://doi.org/10.1186/s12906-021-03349-4

Talhaoui N, Gómez-Caravaca AM, León L, De la Rosa R, Segura-Carretero A, Fernández-Gutiérrez A (2014) Determination of phenolic compounds of ‘Sikitita’olive leaves by HPLC-DAD-TOF-MS. Comparison with its parents ‘Arbequina’and ‘Picual’olive leaves. LWT- Food Sci Technol 58: 28-34. https://doi.org/10.1016/j.lwt.2014.03.014

Tarqui  S, Flores Y, Almanza  GR (2012) Polyoxygenated flavonoids from Baccharis pentlandii. Rev Bol Quím 29: 10-14.

Villagómez JR, Mollinedo P, Almanza GR (2006) (E)-3-prenil-4-hidroxicinamato de metilo de Baccharis santelices Rev Bol Quím 23: 13-18.

Zaratti F, Forno R, Cuarita L, Saavedra P (2003) Seis años de medidas de ozono y radiación ultravioleta en La Paz, Bolivia. Rev Bol Fis 9: 48-51.

Zdero C, Bohlmann F, Solomon J, King R, Robinson H (1989) Ent-clerodanes and other constituents from bolivian Baccharis species. Phytochemistry 28: 531-542. https://doi.org/10.1016/0031-9422(89)80047-0

© 2023 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Ethnobotanical investigation in Soran district, Iraq

J. Pharm. Pharmacogn. Res., vol. 11, no. 1, pp. 1-32, January-February 2023.

DOI: https://doi.org/10.56499/jppres22.1484_11.1.1

Original Article

Medicinal plants used in Soran district Kurdistan region of Iraq, an ethnobotanicals study

[Plantas medicinales utilizadas en el distrito de Soran, región del Kurdistán de Irak, un estudio etnobotánico]

Samiaa J. Abdulwahid-Kurdi1*, Muhsin J. Abdulwahid2, Usman Magaji3, Zeiad A. Aghwan3, Rodziah Atan4,Kasrin A. Hamadamin1

1Department of General Sciences, Faculty of Education, Soran University, Kawa street, 44008 Soran, Erbil, Kurdistan Region, Iraq.

2Salahaddin University Research Center (SURC), Erbil, Kurdistan Region of Iraq.

3Department of Agronomy, Federal University of Kashere, Gombe, Gombe State, Nigeria.

4Department of Halalan Thayyiban Research Centre, University of Islam Sultan Sharif Ali, Brunei Darussalam.

*E-mail: samiaa.abdulwahid@soran.edu.iq, samiaa.abdulwahid@gmail.com

Abstract

Context: The current study, the first of its type, focuses on the ethnobotanical uses of 97 medicinal plant species by the inhabitants in the Soran area, Kurdistan region of Iraq.

Aims: To evaluate local knowledge of medicinal plants and provision of preliminary data on the user-benefit of the accessible plant species in the area.

Methods: Between October 2021 and May 2022, key informant interviews were conducted as part of an ethnobotanical survey. Information about a particular study through face-to-face interviews with 171 participants (98 males and 73 females) was collected. For the therapeutic plants considered in the study, quantitative indices such as use value (UV), family use value (FUV), the relative frequency of citation (RFC), fidelity level (FL), and informant consensus factor (ICF) were applied in addition to detailed notes on each plant species.

Results: The survey discovered 97 plant species and 41 plant families. Leaves were the plant portion that was used the most (44%), while seeds were the least (12%). The most popular three methods of preparation were decoction (52%), row (36%), and crushed (6%). The Olea europaea species had the highest use values (0.82), while Vitex agnus-castus had (0.005). Amaryllidaceae had the highest family use value (1.218), while Asteraceae had (0.005). According to the consensus index, Ficus carica and Datura stramonium had (140.84%) and (1.011%). The digestive tract disease category was shown to have the highest informant consensus factor value out of all disease categories (0.57), while the lowest value ICF was (0.0) for tooth pain.

Conclusions: As a result of the development of natural medicines, this study gives information on the indigenous medicinal plants utilized in the Soran district to treat common illnesses that are ready for additional pharmacological and phytochemical examination. For better use of natural resources, the traditional use of plants requires conservation methods and additional research.

Keywords: ethnobotany; food; medicinal plants; Soran district; traditional medicine.

Resumen

Contexto: El presente estudio se centra en los usos etnobotánicos de 97 especies de plantas medicinales por parte de los habitantes de la zona de Soran, en la región del Kurdistán iraquí.

Objetivos: Evaluar el conocimiento local de las plantas medicinales y aportar datos preliminares sobre el uso-beneficio de las especies vegetales accesibles en la zona.

Métodos: Entre octubre de 2021 y mayo de 2022, se realizaron entrevistas a informantes clave como parte de un estudio etnobotánico. Se recogió información sobre un estudio particular a través de entrevistas cara a cara con 171 participantes (98 hombres y 73 mujeres). Para las plantas terapéuticas consideradas en el estudio, se aplicaron índices cuantitativos como el valor de uso (UV), el valor de uso familiar (FUV), la frecuencia relativa de citación (RFC), el nivel de fidelidad (FL) y el factor de consenso del informante (ICF), además de notas detalladas sobre cada especie vegetal.

Resultados: La encuesta descubrió 97 especies de plantas y 41 familias de plantas. Las hojas fueron la parte de la planta que más se utilizó (44%) mientras que las semillas fueron las menos (12%). Los tres métodos de preparación más populares fueron la decocción (52%), crudo (36%) y el triturado (6%). La especie Olea europaea tuvo los valores de uso más altos (0,82), mientras que Vitex agnus-castus tuvo (0,005). La Amaryllidaceae tuvo el mayor valor de uso de la familia (1,218), mientras que la Asteraceae tuvo (0,005). Según el índice de consenso, Ficus carica y Datura stramonium tuvieron (140,84%) y (1,011%). La categoría de enfermedad del tracto digestivo mostró tener el valor más alto del factor de consenso del informante de todas las categorías de enfermedad (0,57), mientras que el valor más bajo del ICF fue (0,0) para el dolor de muelas.

Conclusiones: Como resultado del desarrollo de las medicinas naturales, este estudio ofrece información sobre las plantas medicinales indígenas utilizadas en el distrito de Soran para tratar enfermedades comunes que están listas para un examen farmacológico y fitoquímico adicional. Para un mejor uso de los recursos naturales, el uso tradicional de las plantas requiere métodos de conservación e investigación adicional.

Palabras Clave: alimentación; distrito de Soran; etnobotánica; medicina tradicional; plantas medicinales.

Citation Format: Abdulwahid-Kurdi SJ, Abdulwahid MJ, Magaji U, Aghwan ZA, Atan R, Hamadamin KA (2023) Medicinal plants used in Soran district Kurdistan region of Iraq, an ethnobotanicals study. J Pharm Pharmacogn Res 11(1): 1–32. https://doi.org/10.56499/jppres22.1484_11.1.1
References

Abbas S, Saeed J (2021) Vascular plants of Bani Harir mountain (Harir intramural bound). Zanco J Pure Appl Sci 33(5): 57–68. https://doi.org/10.21271/ZJPAS.33.5.7

Abdulwahid SJ (2013) Water quality index of Delizhiyan springs and Shawrawa river within Soran district, Erbil, Kurdistan region of Iraq.J Appl Environ Sci 3(1): 40–48.

Abe R, Ohtani K (2013) An ethnobotanical study of medicinal plants and traditional therapies on Batan Island, the Philippines. J Ethnopharmacol 145(2): 554–565. https://doi.org/10.1016/j.jep.2012.11.029

Abuyassin B, Laher I (2016) Diabetes epidemic sweeping the Arab world. World J Diabetes 7(8): 165–174. https://doi.org/10.4239/wjd.v7.i8.165

Acar CA (2021) Green synthesis of zinc oxide nanoparticles using aqueous extract of Achiella millefolium: In vitro anti-cancer potential on lung and colon cancer cells. Turk J Health Sci Life 4(1): 40–45.

Agelet A, Vallès J (2001) Studies on pharmaceutical ethnobotany in the region of Pallars (Pyrenees, Catalonia, Iberian Peninsula). Part I. General results and new or very rare medicinal plants. J Ethnopharmacol 77(1): 57–70. https://doi.org/10.1016/s0378-8741(01)00262-8

Ahmed HM (2016) Ethnopharmacobotanical study on the medicinal plants used by herbalists in Sulaymaniyah Province, Kurdistan, Iraq. J Ethnobiol and Ethnomedicine 12(1): 8. https://doi.org/10.1186/s13002-016-0081-3

Alam MA, Jahan R, Rahman S, Das AK, Rahmatullah M (2011) Antinociceptive and anti-hyperglycemic activity of methanol leaf extract of Cyperus scariosus. Pak J Pharm Sci 24(1): 53–56.

Albuquerque UP, Lucena RF, Monteiro JM, Florentino AT, Cecília de Fátima CBR (2006) Evaluating two quantitative ethnobotanical techniques. Ethnobot Res Appl 4: 51–60.

Al–Douri NA (2014) Some important medicinal plants in Iraq.Int J Adv Herb Alter 2: 10–20.

Alsamri H, Athamneh K, Pintus G, Eid AH, Iratni R (2021) Pharmacological and antioxidant activities of Rhus coriaria L. (Sumac). Antioxidants 10(1): 73. https://doi.org/10.3390/antiox10010073

Anushiravani M, Azad FJ, Taghipour A, Mirsadraee M, Afshari JT, Salari R, Farshchi MK (2020) The effect of Plantago major seed and almond gum on refractory asthma: A proof-of-concept study. J Herb Med 19: 100297. https://doi.org/10.1016/j.hermed.2019.100297

Awan AF, Akhtar MS, Anjum I, Mushtaq MN, Fatima A, Mannan A, Ali I (2020) Anti-oxidant and hepatoprotective effects of Lactuca serriola and its phytochemical screening by HPLC and FTIR analysis. Pak J Pharm Sci 33(9): 2823–2830.

Aziz N, Mehmood MH, Siddiqi HS, Mandukhail SUR, Sadiq F, Maan W, Gilani AH (2009) Antihypertensive, antidyslipidemic and endothelial modulating activities of Orchis mascula. Hypertens Res 32(11): 997–1003. https://doi.org/10.1038/hr.2009.148

Bahmani M, Zargaran A, Rafieian-Kopaei M (2014) Identification of medicinal plants of Urmia for treatment of gastrointestinal disorders. Rev Bras Farmacogn24(4): 468–480. https://doi.org/10.1016/j.bjp.2014.08.001

Bazylko A, Stolarczyk M, Derwińska M, Kiss AK (2012) Determination of the antioxidant activity of extracts and fractions obtained from Galinsoga parviflora and Galinsoga quadriradiata, and a qualitative study of the most active fractions using TLC and HPLC methods. Nat Prod Res 26(17): 1584–1593. https://doi.org/10.1080/14786419.2011.582469

Benninger J, Schneider HT, Schuppan D, Kirchner T, Hahn EG (1999) Acute hepatitis induced by greater celandinee (Chelidonium majus). Gastroenterology 117(5): 1234–1237. https://doi.org/10.1016/s0016-5085(99)70410-5

Boscaro V, Boffa L, Binello A, Amisano G, Fornasero S, Cravotto G, Gallicchio M (2018) Antiproliferative, proapoptotic, antioxidant and antimicrobial effects of Sinapis nigra L. and Sinapis alba L. extracts. Molecules 23(11): 3004. https://doi.org/10.3390/molecules23113004

Bradusty M (2017) Soran Health Directorate is Concerned about Erbil’s Health. News Wishe. https://www.wishe.net/details.aspx?=hewal&jmare=8589&Jor=9 [23 June 2017].

Bussmann RY, Paniagua Zambrana S, Sikharulidze Z, Kikvidze D, Kikodze D, Tchelidze M, Khutsishvili K, Batsatsashvili RE (2016) A comparative ethnobotany of Khevsureti, Samtskhe-Javakheti, Tusheti, Svaneti, and Racha-Lechkhumi, Republic of Georgia (Sakartvelo), Caucasus. J Ethnobiol Ethnomed 12: 43. https://doi.org/10.1186/s13002-016-0110-2

Capistrano I R, Wouters A, Lardon F, Gravekamp C, Apers S, Pieters L (2015) In vitro and in vivo investigations on the antitumour activity of Chelidonium majus. Phytomedicine 22(14): 1279–1287. https://doi.org/10.1016/j.phymed.2015.10.013

Çolak F, Savaroğlu F, İlhan S (2009) Antibacterial and antifungal activities of Arum maculatum L. leaves extracts. J Appl Biol Sci 3(3): 13–16.

Czinner E, Hagymasi K, Blazovics A, Kery A, Szőke É, Lemberkovics E (2000) In vitro antioxidant properties of Helichrysum arenarium (L.) Moench. J Ethnopharmacol 73(3): 437–443. https://doi.org/10.1016/s0378-8741(00)00304-4

Dashtban M, Sarir H, Omidi A (2016) The effect of Prosopis farcta beans extract on blood biochemical parameters in streptozotocin-induced diabetic male rats. Adv Biomed Res 5: 116. https://doi.org/10.4103/2277-9175.185575

El-Mallah MH, El-Shami SM, Hassanein MM (2003) Detailed studies on some lipids of Silybum marianum (L.) seed oil. Grasas y Aceites 54(4): 397-402. https://doi.org/10.3989/gya.2003.v54.i4.227

Erbil Governorate (2014) Soran District. Erbil Governorate Main Report. https://web.archive.org/web/20140717073706/http://hawlergov.org/ku/region.php?id=1330758837 [17 July 2104].

Friedman J, Yaniv Z, Dafni A, Palewitch D (1986) A preliminary classification of the healing potential of medicinal plants, based on a rational analysis of an ethnopharmacological field survey among Bedouins in the Negev Desert, Israel. J Ethnopharmacol 16(2-3): 275–287. https://doi.org/10.1016/0378-8741(86)90094-2

Gañán NA, Dias AM, Bombaldi F, Zygadlo JA, Brignole EA, de Sousa HC, Braga ME (2016) Alkaloids from Chelidonium majus L.: Fractionated supercritical CO2 extraction with co-solvents.Sep Purif Technol 165: 199–207. https://doi.org/10.1016/j.seppur.2016.04.006

Gordon A, Hobbs DA, Bowden DS, Bailey MJ, Mitchell J, Francis AJ, Roberts SK (2006) Effects of Silybum marianum on serum hepatitis C virus RNA, alanine aminotransferase levels and well‐being in patients with chronic hepatitis C. J Gastroenterol Hepatol 21(1 Pt 2): 275–280. https://doi.org/10.1111/j.1440-1746.2006.04138.x

Gunes C (2019) The Kurdish conflict in Iraq: towards a sustainable solution. In: The Kurds in a New Middle East: Palgrave Macmillan, Cham, pp. 21–39. https://doi.org/10.1007/978-3-030-00539-9_2

Gunjan M, Naing TW, Saini RS, Ahmad A, Naidu JR, Kumar I (2015) Marketing trends & future prospects of herbal medicine in the treatment of various diseases. World J Pharm Res 4(9): 132–155.

Hamad R (2020) A remote sensing and GIS-based analysis of urban sprawl in Soran District, Iraqi Kurdistan. S N Appl Sci 2: 24. https://doi.org/10.1007/s42452-019-1806-4

Harris DR (1989) An evolutionary continuum of people-plant interaction. In: Foraging and farming, eds. D. R. Harris and G. C. Hillman. London: Routledge. https://doi.org/10.4324/9781315746425

Heinrich M, Ankli A, Frei B, Weimann C (1998) Medicinal plants in Mexico: Healers consensus and cultural importance. Soc Sci Med 47(11): 1859–1871. https://doi.org/10.1016/s0277-9536(98)00181-6

Hosseini SH, Sadeghi Z, Hosseini SV, Bussmann RW (2022) Ethnopharmacological study of medicinal plants in Sarvabad, Kurdistan province, Iran. J Ethnopharmacol 288: 114985. https://doi.org/10.1016/j.jep.2022.114985

Huerta-Franco MR, Vargas-Luna M, Tienda P, Delgadillo-Holtfort I, Balleza-Ordaz M, Flores-Hernandez C (2013) Effects of occupational stress on the gastrointestinal tract. World J Gastrointest Pathophysiol 4(4): 108. https://doi.org/10.4291/wjgp.v4.i4.108

Huo CH, Li Y, Zhang ML, Wang YF, Zhang Q, Qin F, Kiyota H (2013) Cytotoxic flavonoids from the flowers of Achillea millefolium. Chem Nat Compd 48(6): 958–962. https://doi.org/10.1007/s10600-013-0438-y

Ismail Y (2021) The Roots of Coexistence and Religious Tolerance in Kurdistan. Kurdistan 24 News https://www.kurdistan24.net/en/story/24908-The-roots-of-coexistence-and-religious-tolerance-in-Kurdistan [02 July 2021].

Jadid N, Kurniawan E, Himayani S, Prasetyowati I, Purwani I, Muslihatin W, Tjahjaningrum D (2020) An ethnobotanical study of medicinal plants used by the Tengger tribe in Ngadisari village, Indonesia. PloS One 15(7): e0235886. https://doi.org/10.1371/journal.pone.0235886

Jalalpure SS, Mandavkar YD, Khalure PR, Shinde GS, Shelar PA, Shah AS (2011) Antiarthritic activity of various extracts of Mesua ferrea Linn. seed. J Ethnopharmacol 138(3): 700–704. https://doi.org/10.1016/j.jep.2011.09.042

Janbaz KH, Latif MF, Saqib F, Imran I, Zia-Ul-Haq M, De Feo V (2013) Pharmacological effects of Lactuca serriola L. in experimental model of gastrointestinal, respiratory, and vascular ailments. Evid Based Complement Alternat Med2013: 304394. https://doi.org/10.1155/2013/304394

Karimi E, Oskoueian E, Karimi A, Noura R, Ebrahimi M (2018) Borago officinalis L. flower: a comprehensive study on bioactive compounds and its health-promoting properties. J Food Meas Charact 12(2): 826–838. https://doi.org/10.1007/s11694-017-9697-9

Karwan M, Abdullah O, Amin A, Hasan B, Mohamed Z, Sulaiman L, Shekha M, Najmuldeen H, Barzingi B, Salih A, Mahmood D, Othman H, Rahman F, Mohammad D, Salih F, Ali SK, Housein Z, Mohamad T, Mahmood K, Othman G, Aali M, Qader G, Hussen B, Awla F, Qadir F, Taher D, Salihi A (2021) Cancer Statistics in Kurdistan Region of Iraq: A Tale of Two Cities. Res Squre, Preprint: 1–18. https://doi.org/10.21203/rs.3.rs-142129/v1

Kavak C, Baştürk A (2020) Antioxidant activity, volatile compounds and fatty acid compositions of Cephalaria syriaca seeds obtained from different regions in Turkey. Grasas y Aceites 71(4): e379. https://doi.org/10.3989/gya.0913192

Khan I, AbdElsalam NM, Fouad H, Tariq A, Ullah R, Adnan M (2014) Application of ethnobotanical indices on the use of traditional medicines against common diseases. Evid Based Complementary Altern Med 2014: 635371. https://doi.org/10.1155/2014/635371

Khmil M, Khmil S, Marushchak M (2020) Hormone imbalance in women with infertility caused by polycystic ovary syndrome: Is there a connection with body mass index. Open Access Maced J Med Sci 8(B): 731–737. https://doi.org/10.3889/oamjms.2020.4569

Khodabande Z, Jafarian V, Sariri R (2017) Antioxidant activity of Chelidonium majus extract at phenological stages. Appl Biol Chem 60(5): 497–503. https://doi.org/10.1007/s13765-017-0304-x

Khoja AA, Andrabi AH, Mir RA (2022) Traditional medicine in the treatment of gastrointestinal diseases in northern part of Kashmir Himalayas. Ethnobot Res Appl 23: 22. http://dx.doi.org/10.32859/era.23.22.1-17

Kolak U, Boğa M, Uruşak EA, Ulubelen A (2011) Constituents of Plantago major subsp. intermedia with antioxidant and anticholinesterase capacities. Turk J Chem 35(4): 637–645. http://dx.doi.org/10.3906/kim-1102-990

Kim HG, Nam YH, Jung YS, Oh SM, Nguyen TN, Lee MH, Baek NI (2021). Aurones and flavonols from Coreopsis lanceolata L. flowers and their anti-oxidant, pro-inflammatory inhibition effects, and recovery effects on alloxan-induced pancreatic islets in zebrafish. Molecules 26: 6098. https://doi.org/10.3390/molecules26206098

Kos B, Grčman H, Leštan D (2003) Phytoextraction of lead, zinc and cadmium from soil by selected plants. Plant Soil Environ 49(12): 548–553. http://dx.doi.org/10.17221/4192-PSE

Kumar KS, Bhowmik D, Chiranjib B, Tiwari P (2010) Allium cepa: A traditional medicinal herb and its health benefits. J Chem Pharm Res 2(1): 283–291.

Mahmood AM, Sallo AK, Hasan MA (2014) Chemical components and antibacterial activity of Gundelia tournefortii L. Compositae/Asteraceae (Iraq, Kurdistan Region, Sulaymaniyah, Penjwin area, “Kokhalan”). J Indian Chem Soc91: 2107–2111. https://doi.org/10.5281/zenodo.5741404

Mao Z, Gan C, Zhu J, Ma N, Wu L, Wang L, Wang X (2017) Anti-atherosclerotic activities of flavonoids from the flowers of Helichrysum arenarium L. MOENCH through the pathway of anti-inflammation. Bioorg Med Chem Lett 27(12): 2812–2817. https://doi.org/10.1016/j.bmcl.2017.04.076

Mitrović PM, Stamenković OS, Banković-Ilić l, Djalović IG, Nježić ZB, Farooq M, Veljković VB (2020) White mustard (Sinapis alba L.) oil in biodiesel production: A review. Front Plant Sci 11: 299. https://doi.org/10.3389/fpls.2020.00299

Molares S, Ladio A (2009) Ethnobotanical review of the Mapuche medicinal flora: Use patterns on a regional scale. J Ethnopharmacol 122(2): 251–260. https://doi.org/10.1016/j.jep.2009.01.003

Muhamad S (2020) Economic Crunch Revives Farming in Soran. Rudaw Bus https://www.rudaw.net/english/business/050720201 [05 July 2020].

Najem M, Nassiri L, Ibijbijen J (2021) Vernacular names of plants between diversity and potential risks of confusion: Case of toxic plants used in medication in the central Middle Atlas, Morocco. J Pharm Pharmacogn Res 9(2): 222–250. https://doi.org/10.56499/jppres20.950_9.2.222

Nakyai W, Pabuprapap W, Sroimee W, Ajavakom V, Yingyongnarongkul BE, Suksamrarn A (2021) Anti-acne vulgaris potential of the ethanolic extract of Mesua ferrea L. flowers. Cosmetics 8: 107. https://doi.org/10.3390/cosmetics8040107

Nugraha RV, Ridwansyah H, Ghozali M, Khairani AF, Atik N (2020) Traditional herbal medicine candidates as complementary treatments for COVID-19: A review of their mechanisms, pros and cons. Evid Based Complement Alternat Med 2020: 2560645. https://doi.org/10.1155/2020/2560645

Opuni KF, Togoh G, Frimpong-Manso S, Adu-Amoah D, Alkanji O, Boateng KP (2021) Monitoring of residual solvent contamination in herbal medicinal products in Ghana: A pilot study. Sci Afr 13: e00825. https://doi.org/10.1016/j.sciaf.2021.e00825

Özgen U, Kaya Y, Houghton P (2012) Folk medicines in the villages of Ilıca District (Erzurum, Turkey). Turk J Biol 36(1): 93–106. https://doi.org/10.3906/biy-1009-124

Payyappallimana U (2010) Role of traditional medicine in primary health care: an overview of perspectives and challenges. Yokohama J Soc Sci 14: 57–77.

Piyaviriyakul S, Siripong P, Vallisuta O (2014) HPTLC simultaneous quantification of triterpene acids for quality control of Plantago major L. and evaluation of their cytotoxic and antioxidant activities. Ind Crops Prod 60: 239–246. https://doi.org/10.1016/j.indcrop.2014.06.020

Polat R, Cakilcioglu U, Satıl F (2013) Traditional uses of medicinal plants in Solhan (Bingöl—Turkey). J Ethnopharmacol 148(3): 951–963. https://doi.org/10.1016/j.jep.2013.05.050

Rahman M, Khatun A, Liu L, Barkla BJ (2018) Brassicaceae mustards: Traditional and agronomic uses in Australia and New Zealand. Molecules 23(1): 231. https://doi.org/10.3390/molecules23010231

Rajaei P, Mohamadi N (2012) Ethnobotanical study of medicinal plants of Hezar mountain allocated in southeast of Iran. Iran J Pharm Res 11(4): 1153–1167.

Rzgar M (2021) Soran. Retrieved from Zanyare. https://zaniary.com/blog/6106acc700727 [01 August 2021].

Segal TR, Giudice LC (2019) Before the beginning: environmental exposures and reproductive and obstetrical outcomes. Fertil Steril 112(4): P613–621. https://doi.org/10.1016/j.fertnstert.2019.08.001

Shaker E, Mahmoud H, Mnaa S (2010) Silymarin, the antioxidant component and Silybum marianum extracts prevent liver damage. Food Chem Toxicol 48(3): 803–806. https://doi.org/10.1016/j.fct.2009.12.011

Sõukand RY, Hrynevich J, Prakofjewa T, Valodzina I, Vasilyeva J, Paciupa R, Shrubok A, Hlushko A, Knureva Y, Litvinava Y, Vyskvarka S, Silivonchyk H, Paulava A, Kõiva M, Kalle R (2017) Use of cultivated plants and non-plant remedies for human and animal homemedication in Liubań district, Belarus. J Ethnobiol Ethnomed 13(1): 54. https://doi.org/10.1186/s13002-017-0183-6

Sreekeesoon DP, Mahomoodally MF (2014) Ethnopharmacological analysis of medicinal plants and animals used in the treatment and management of pain in Mauritius. J Ethnopharmacol157: 181–200. https://doi.org/10.1016/j.jep.2014.09.030

Stanisavljević N, Soković Bajić S, Jovanović Ž, Matić I, Tolinački M, Popović D, Popović N, Terzić-Vidojević A, Golić N, Beškoski V, Samardžić J (2020) Antioxidant and antiproliferative activity of Allium ursinum and their associated microbiota during simulated in vitro digestion in the presence of food matrix. Front Microbiol 11: 601616. https://doi.org/10.3389/fmicb.2020.601616

Szema AM, Reeder RJ, Harrington AD, Schmidt M, Liu J, Golightly M, Rueb T, Hamidi SA (2014) Iraq dust is respirable, sharp, metal-laden, and induces lung inflammation with fibrosis in mice via IL-2 upregulation and depletion of regulatory T cells.J Occup Environ Med 56(3): 243–251. https://doi.org/10.1097/jom.0000000000000119

Tangjitman K, Wongsawad C, Kamwong K, Sukkho T, Trisonthi C (2015) Ethnomedicinal plants used for digestive system disorders by the Karen of northern Thailan. J Ethnobiol Ethnomed 11(1): 27. https://doi.org/10.1186/s13002-015-0011-9

Teall EK (2014) Medicine and doctoring in ancient Mesopotamia. Grand Valley J Hist 3(1): 2–5.

Tetik F, Civelek S, Cakilcioglu U (2013) Traditional uses of some medicinal plants in Malatya (Turkey). J Ethnopharmacol 146(1): 331–346. https://doi.org/10.1016/j.jep.2012.12.054

Tounekti T, Mahdhi M, Khemira H (2019) Ethnobotanical study of indigenous medicinal plants of Jazan region, Saudi Arabia. Evid Based Complement Alternat Med 2019: 3190670. https://doi.org/10.1155/2019/3190670

Trotter RT, Logan MH (1986) Informant consensus: A new approach for identifying potentially effective medicinal plants. In: Plants in Indigenous Medicine & Diet. Edited by Etkin NL. Redgrave Publishing Company, NY, USA: Bedford Hill, pp. 91–112. http://dx.doi.org/10.4324/9781315060385-6

Tugume P, Kakudidi EK, Buyinza M, Namaalwa J, Kamatenesi M, Mucunguzi P, Kalema J (2016) Ethnobotanical survey of medicinal plant species used by communities around Mabira Central Forest Reserve, Uganda. J Ethnobiol Ethnomedicine 12(1): 5. https://doi.org/10.1186/s13002-015-0077-4

Upadhya V, Hegde HV, Bhat S, Kholkute SD (2014) Non-codified traditional medicine practices from Belgaum Region in Southern India: present scenario. JEthnobiol Ethnomed 10(1): 49. https://doi.org/10.1186/1746-4269-10-49

Wali ZZ (2021) Budget quagmire: The Erbil-Baghdad never-ending problem. Rudaw News Analy. 2021. https://www.rudaw.net/english/analysis/24052021 [24 May 2021].

Weil AT (1981) The therapeutic value of coca in contemporary medicine. J Ethnopharmacol 3(2-3): 367–376. https://doi.org/10.1016/0378-8741(81)90064-7

WHO (2000) Programme on Traditional Medicine: General Guidelines for Methodologies on Research and Evaluation of Traditional Medicine. Geneva, Switzerland: World Health Organization. WHO/EDM/TRM/2000.1.

WHO (2012) WorldHealth Statistics: A Snapshot of Global Health. Organization Mundial De La Salud. Geneva, Switzerland: World Health Organization. WHO/IER/HSI/12.1.

Wilasrusmee C, Kittur S, Shah G, Siddiqui J, Bruch D, Wilasrusmee S, Kittur DS (2002) Immunostimulatory effect of Silybum marianum (milk thistle) extract. Med Sci Monit Int Med J Exp Clin Res8(11): BR439–443.

Yabrir B, Touati M, Adli B, Bezini E, Ghafoul M, Khalifa S, Guit B (2018) Therapeutic use of spontaneous medicinal flora from an extreme environment (dune cordon) in Djelfa region, Algeria. J Pharm Pharmacogn Res 6(5): 358–373.

Zenderland J, Hart R, Bussmann RW, Paniagua Zambrana NY, Sikharulidze S, Kikvidze Z, Kikodze D, Tchelidze D, Khutsishvili M, Batsatsashvili K (2019) The use of ‘use value’: Quantifying importance in ethnobotany. Econ Bot 73(3): 293–303. https://doi.org/10.1007/s12231-019-09480-1

© 2023 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Polyether ionophores as potential antimalarial

J. Pharm. Pharmacogn. Res., vol. 10, no. 6, pp. 1139-1148, November-December 2022.

DOI: https://doi.org/10.56499/jppres22.1478_10.6.1139

Original Article

Potential of polyether ionophore compounds as antimalarials through inhibition on Plasmodium falciparum glutathione S-transferase by molecular docking studies

[Potencial de los compuestos ionóforos de poliéter como antimaláricos mediante la inhibición de glutatión S-transferasa de Plasmodium falciparum a través de estudios de acoplamiento molecular]

Alfian Wika Cahyono1,2, Icha Farihah Deniyati Faratisha1, Nabila Erina Erwan1,3, Rivo Yudhinata Brian Nugraha1,4, Ajeng Maharani Putri1,3, Loeki Enggar Fitri1,4*

1Malaria Research Group, Faculty of Medicine, Universitas Brawijaya, Malang, East Java, 65145, Indonesia.

2Doctoral Program in Medical Science, Faculty of Medicine, Universitas Brawijaya, Malang, East Java, 65145, Indonesia.

3Master Program in Biomedical Science, Faculty of Medicine, Universitas Brawijaya, Malang, East Java, 65145, Indonesia.

4Department of Parasitology, Faculty of Medicine, Universitas Brawijaya, Malang, East Java, 65145, Indonesia.

*E-mail: lukief@ub.ac.id

Abstract

Context: Malaria is still a serious global health problem due to the development of drug resistance. It is necessary to find new drugs with renewable mechanisms that are effective in killing parasites. Our previous research has analyzed more than one compound of polyether ionophore group in ethyl acetate Streptomyces hygroscopicus subsp. hygroscopicus extract. Polyether ionophore is known to have a similar mechanism of action to chloroquine which is potent in inhibiting Plasmodium falciparum glutathione S-transferase (PfGST).

Aims: To evaluate the potential effect of polyether ionophore toward PfGST as a target protein through molecular docking.

Methods: PfGST was obtained from Protein Data Bank. Test ligands (polyether ionophore) and control ligands (chloroquine) were obtained from PubChem. Pharmacokinetic analysis was done using SwissADME, molecular docking using PyRx 0.9, visualization using LigPlot and PyMOL, and molecular dynamics using YASARA for the best ligand activity.

Results: Lenoremycin had the highest binding affinity to PfGST (-8.53 kcal/mol) among other polyether ionophores, and nigericin had the best residue bonding with hydrophobic and hydrogen with a binding affinity of -8.25 kcal/mol compared to chloroquine complex in molecular docking and molecular dynamic simulation.

Conclusions: Polyether ionophore could serve as an antimalarial agent better than chloroquine, with nigericin as the best compound candidate in inhibiting PfGST compared to other polyether ionophores.

Keywords: malaria; molecular docking; PfGST; polyether ionophore; Streptomyces hygroscopicus.

jppres_pdf_free

Resumen

Contexto: La malaria sigue siendo un grave problema sanitario mundial debido al desarrollo de resistencia a los fármacos. Es necesario encontrar nuevos fármacos con mecanismos renovables que sean eficaces para matar a los parásitos. Nuestra investigación anterior ha analizado más de un compuesto del grupo ionóforo poliéter en el extracto de acetato de etilo de Streptomyces hygroscopicus subsp. hygroscopicus. Se sabe que el poliéter ionóforo tiene un mecanismo de acción similar al de la cloroquina, que es potente inhibidor de la gutatión S-transferasa de Plasmodiun falciparum (PfGST).

Objetivos: Evaluar el efecto potencial del poliéter ionóforo hacia la PfGST como proteína diana a través del acoplamiento molecular.

Métodos: PfGST se obtuvo del Banco de Datos de Proteínas. Los ligandos de prueba (poliéter ionóforo) y los ligandos de control (cloroquina) se obtuvieron de PubChem. El análisis farmacocinético se realizó con SwissADME, el docking molecular con PyRx 0.9, la visualización con LigPlot y PyMOL, y la dinámica molecular con YASARA para la mejor actividad del ligando.

Resultados: La lenoremycina tuvo la mayor afinidad de unión a PfGST (-8,53 kcal/mol) entre otros poliéteres ionóforos, y la nigericina tuvo la mejor unión de residuos con hidrófobos e hidrógenos con una afinidad de unión de -8,25 kcal/mol en comparación con el complejo de cloroquina en el docking molecular y la simulación dinámica molecular.

Conclusiones: El ionóforo poliéter podría servir como agente antimalárico mejor que la cloroquina, siendo la nigericina el mejor candidato para inhibir el PfGST en comparación con otros ionóforos poliéter.

Palabras Clave: acoplamiento molecular; ionóforo poliéter; malaria; PfGST; Streptomyces hygroscopicus.

jppres_pdf_free
Citation Format: Cahyono AW, Faratisha IFD, Erwan NE, Nugraha RYB, Putri AM, Fitri LE (2022) Potential of polyether ionophore compounds as antimalarials through inhibition on Plasmodium falciparum glutathione S-transferase by molecular docking studies. J Pharm Pharmacogn Res 10(6): 1139–1148. https://doi.org/10.56499/jppres22.1478_10.6.1139
References

Abkar AH, Djati MS, Widodo W (2021) In silico study to predict the potential of beta asarone, methyl piperonylketone, coumaric acid in Piper crocatum as anticancer agents. J Exp Life Sci 11: 89–99. https://doi.org/10.21776/ub.jels.2021.011.03.04

Adovelande J, Schrével J (1996) Carboxylic ionophores in malaria chemotherapy: The effects of monensin and nigericin on Plasmodium falciparum in vitro and Plasmodium vinckei petteri in vivo. Life Sci 59: 309-315. https://doi.org/10.1016/s0024-3205(96)00514-0

Fitri LE, Alkarimah A, Cahyono AW, Lady WN, Endharti AT, Nugraha RYB (2019) Effect of metabolite extract of Streptomyces hygroscopicus subsp. hygroscopicus on Plasmodium falciparum 3D7 in vitro. Iran J Parasitol 14: 444–452.

Gumila C, Ancelin ML, Delort AM, Jeminet G, Vial HJ (1997) Characterization of the potent in vitro and in vivo antimalarial activities of ionophore compounds. Antimicrob Agents Chemother 41: 523–529. https://doi.org/10.1128/AAC.41.3.523

Hartuti ED, Inaoka DK, Komatsuya K, Miyazaki Y, Miller RJ, Xinying W, Sadikin M, Prabandari EE, Waluyo D, Kuroda M, Amalia E, Matsuo Y, Nugroho NB, Saimoto H, Pramisandi A, Watanabe YI, Mori M, Shiomi K, Balogun EO, Shiba T, Harada S, Nozaki T, Kita K (2018) Biochemical studies of membrane bound Plasmodium falciparum mitochondrial L-malate:quinone oxidoreductase, a potential drug target. Biochim Biophys Acta Bioenerg 1859: 191–200. https://doi.org/10.1016/j.bbabio.2017.12.004

Harwaldt P, Rahlfs S, Becker K (2002) Glutathione S-transferase of the malarial parasite Plasmodium falciparum: Characterization of a potential drug target. Biol Chem 383: 821–830. https://doi.org/10.1515/BC.2002.086

Hiller N, Fritz-Wolf K, Deponte M, Wende W, Zimmermann H, Becker K (2006) Plasmodium falciparum glutathione S-transferase–structural and mechanistic studies on ligand binding and enzyme inhibition. Protein Sci 15: 281–289. https://doi.org/10.1110/ps.051891106

Huczyński A (2012) Polyether ionophores—promising bioactive molecules for cancer therapy. Bioorg Med Chem Lett 22: 7002–7010. https://doi.org/10.1016/j.bmcl.2012.09.046

Kevin II DA, Meujo DA, Hamann MT (2009) Polyether ionophores: Broad-spectrum and promising biologically active molecules for the control of drug-resistant bacteria and parasites. Expert Opin Drug Discov 4: 109–146. https://doi.org/10.1517/17460440802661443

Liebau E, Bergmann B, Campbell AM, Teesdale-Spittle P, Brophy PM, Lüersen K, Walter RD (2002) The glutathione S-transferase from Plasmodium falciparum. Mol Biochem Parasitol 124: 85–90. https://doi.org/10.1016/s0166-6851(02)00160-3

Na M, Meujo DAF, Kevin D, Hamann MT, Anderson M, Hill RT (2008) A new antimalarial polyether from a marine Streptomyces sp. H668. Tetrahedron Lett 49: 6282–6285. https://doi.org/10.1016/j.tetlet.2008.08.052

Novilla MN, McClary D, Laudert SB (2017) Chapter 29 – Ionophores, in: Gupta, R.C. (Ed.), Reproductive and Developmental Toxicology (2th Edition). Academic Press, pp. 503–518. https://doi.org/10.1016/B978-0-12-804239-7.00029-9

Otoguro K, Kohana A, Manabe C, Ishiyama A, Ui H, Shiomi K, Yamada H, Omura S (2001) Potent antimalarial activities of polyether antibiotic, X-206. J Antibiot (Tokyo) 54: 658–663. https://doi.org/10.7164/antibiotics.54.658

Perbandt M, Eberle R, Fischer-Riepe L, Cang H, Liebau E, Betzel C (2015) High resolution structures of Plasmodium falciparum GST complexes provide novel insights into the dimer–tetramer transition and a novel ligand-binding site. J Struct Biol 191: 365–375. https://doi.org/10.1016/j.jsb.2015.06.008

PubChem (2008) Sodium carriomycin. Available: https://pubchem.ncbi.nlm.nih.gov/compound/23698022 [Accessed 24 August 2021].

PubChem (2007) Septamycin sodium salt. Available: https://pubchem.ncbi.nlm.nih.gov/compound/23693333 [Accessed 24 August 2021].

PubChem (2006) Lenoremycin. Available: https://pubchem.ncbi.nlm.nih.gov/compound/6441669 [Accessed 24 August 2021].

PubChem (2005a) Nigericin. Available: https://pubchem.ncbi.nlm.nih.gov/compound/34230 [Accessed 24 August 2021].

PubChem (2005b) Dianemycin. Available: https://pubchem.ncbi.nlm.nih.gov/compound/5475287 [Accessed 24 August 2021].

PubChem (2005c) Etheromycin. Available: https://pubchem.ncbi.nlm.nih.gov/compound/3042207 [Accessed 24 August 2021].

Rajendran V, Rohra S, Raza M, Hasan GM, Dutt S, Ghosh PC (2015) Stearylamine liposomal delivery of monensin in combination with free artemisinin eliminates blood stages of Plasmodium falciparum in culture and P. berghei infection in murine malaria. Antimicrob Agents Chemother 60: 1304–1318. https://doi.org/10.1128/AAC.01796-15

Raphemot R, Posfai D, Derbyshire ER (2016) Current therapies and future possibilities for drug development against liver-stage malaria. J Clin Invest 126: 2013–2020. https://doi.org/10.1172/JCI82981

Rivo YB, Alkarimah A, Ramadhani NN, Cahyono AW, Laksmi DA, Winarsih S, Fitri LE (2013) Metabolite extract of Streptomyces hygroscopicus Hygroscopicus inhibit the growth of Plasmodium berghei through inhibition of ubiquitin-proteasome system. Trop Biomed 30: 291–300.

Rutkowski J, Brzezinski B (2013) Structures and properties of naturally occurring polyether antibiotics. Biomed Res Int 2013: 162513. https://doi.org/10.1155/2013/162513

World Health Organization (2020) World malaria report: 20 years of global progress and challenges. Available: https://www.who.int/publications/i/item/9789240015791 [Accessed 25 August 2021].

© 2022 Journal of Pharmacy & Pharmacognosy Research (JPPRes)