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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


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.


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

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© 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


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.


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

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© 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


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.


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

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© 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


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


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.


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

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© 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


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.


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

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© 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


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.


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

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

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© 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


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.


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

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© 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


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).


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

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© 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


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.


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

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© 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


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.



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.

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

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