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Sonchus arvensis L. against SARS-CoV-2 infection

Pharmaceutical Science, , , , , ,

J. Pharm. Pharmacogn. Res., vol. 10, no. 6, pp. 1126-1138, November-December 2022.

DOI: https://doi.org/10.56499/jppres22.1489_10.6.1126

Original Article

Molecular simulation of compounds from n-hexane fraction of Sonchus arvensis L. leaves as SARS-CoV-2 antiviral through inhibitor activity targeting strategic viral protein

[Simulación molecular de compuestos de la fracción de n-hexano de las hojas de Sonchus arvensis L. como antivirales del SARS-CoV-2 a través de la actividad inhibidora dirigida a la proteína viral estratégica]

Dwi Kusuma Wahyuni1,2*, Sumrit Wacharasindhu3, Wichanee Bankeeree2, Hunsa Punnapayak2, Hery Purnobasuki1, Junairiah1, Arif NM Ansori4, Viol Dhea Kharisma1,5, Arli Aditya Parikesit6, Listyani Suhargo1*, Sehanat Prasongsuk1,2*

1Department of Biology, Faculty of Science and Technology, Universitas Airlangga Surabaya, East Java, 60115, Indonesia.

2Plant Biomass Utilization Research Unit, Department of Botany, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand.

3Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok,10330, Thailand.

4Professor Nidom Foundation, Surabaya, East Java, 60115, Indonesia.

5Computational Virology Research Unit, Division of Molecular Biology and Genetics, Generasi Biologi Indonesia Foundation, Gresik, East Java, 61171, Indonesia.

6Department of Bioinformatics, School of Life Science, Indonesia International Institute for Life Sciences, Jakarta, 13210, Indonesia.

*E-mail: dwi-k-w@fst.unair.ac.id (DKW), listyani-s@fst.unair.ac.id (LS), sehanat.p@chula.ac.th (SP)

Abstract

Context: COVID-19 was caused by the spread and transmission of SARS-CoV-2 at the end of 2019 until now. The problem comes when antiviral drugs have not yet been found and patients infected with SARS-CoV-2 can trigger a cytokine storm condition due to the effects of viral replication. Indonesia has various kinds of medicinal plants, such as Sonchus arvensis L., which are used as medicinal plants.

Aims: To analyze the activity of the inhibitor as SARS-CoV-2 antiviral agents from n-hexane fractions of S. arvensis leaves.

Methods: The sample was collected from GC-MS analysis, PubChem, and Protein Databank database, then drug-likeness identification using Lipinski Rule of Five server and bioactive prediction of bioactive compounds as inhibitor activity was conducted by Molinspiration server. Furthermore, the docking simulation was performed using PyRx 0.9.9 software to determine the binding activity, molecular interaction by Discovery Studio software to identify position and interaction type, 3D molecular visualization by PyMol 2.5. software, and dynamic by CABS-flex 2.0 server to predict interaction stability.

Results: α-Amyrin and β-amyrin from n-hexane fractions of S. arvensis leaves had activity as SARS-CoV-2 inhibitors through interactions on helicase, RdRp, Mpro, and RBD-Spike, both compounds had more negative binding affinity than control drug and can produce stable chemical bond interactions in the ligand-protein complexes. However, the results were merely computational, so they must be validated through an in vivo and in vitro research approach.

Conclusions: Sonchus arvensis L. leaves were predicted to have SARS-CoV-2 antiviral through inhibitor activity by α-amyrin and β-amyrin.

Keywords: antiviral; bioinformatics; SARS-CoV-2; Sonchus arvensis L.

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Resumen

Contexto: La propagación y la transmisión del SARS-CoV-2 han sido causadas por el COVID-19 desde finales de 2019 hasta ahora. El problema surge cuando aún no se han encontrado medicamentos antivirales y los pacientes infectados por el SARS-CoV-2 pueden desencadenar una condición de tormenta de citocinas debido a los efectos de la replicación viral. Indonesia tiene varios tipos de plantas medicinales, como Sonchus arvensis L., que se utilizan como plantas medicinales.

Objetivos: Analizar la actividad inhibidora de SARS-CoV-2 de fracciones de n-hexano de las hojas de S. arvensis.

Métodos: La muestra se recogió del análisis GC-MS, PubChem y la base de datos Protein Databank, luego se identificó la similitud de los fármacos utilizando el servidor Lipinski Rule of Five y se realizó la predicción de los compuestos bioactivos como actividad inhibidora mediante el servidor Molinspiration. Además, se realizó la simulación de acoplamiento mediante el software PyRx 0.9.9 para determinar la actividad de unión, la interacción molecular mediante el software Discovery Studio para identificar la posición y el tipo de interacción, la visualización molecular 3D mediante el software PyMol 2.5. y la dinámica mediante el servidor CABS-flex 2.0 para predecir la estabilidad de la interacción.

Resultados: La α-amirina y la β-amirina de las fracciones de n-hexano de las hojas de S. arvensis tuvieron actividad como inhibidores del SARS-CoV-2 a través de las interacciones en la helicasa, RdRp, Mpro y RBD-Spike, ambos compuestos tuvieron más afinidad de unión negativa que el fármaco de control y pueden producir interacciones de enlace químico estables en los complejos ligando-proteína. Sin embargo, los resultados fueron meramente computacionales, por lo que deben ser validados mediante un enfoque de investigación in vivo e in vitro.

Conclusiones: Se predijo que las hojas de S. arvensis tienen actividad antiviral contra el SARS-CoV-2 a través de la actividad inhibidora de la α-amirina y la β-amirina.

Palabras Clave: antiviral; bioinformática; SARS-CoV-2; Sonchus arvensis L.

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Citation Format: Wahyuni DK, Wacharasindhu S, Bankeeree W, Punnapayak H, Parikesit AA, Kharisma VD, Ansori ANM, Suhargo L, Prasongsuk S (2022) Molecular simulation of compounds from n-hexane fraction of Sonchus arvensis L. leaves as SARS-CoV-2 antiviral through inhibitor activity targeting strategic viral protein. J Pharm Pharmacogn Res 10(6): 1126–1138. https://doi.org/10.56499/jppres22.1489_10.6.1126
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© 2022 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Valproic acid concentrations in people with epilepsy

Pharmaceutical Science, , , , ,

J. Pharm. Pharmacogn. Res., vol. 10, no. 6, pp. 1117-1125, November-December 2022.

DOI: https://doi.org/10.56499/jppres22.1500_10.6.1117

Original Article

Serum concentrations of valproic acid in people with epilepsy: Clinical implication

[Concentraciones séricas de ácido valproico en personas con epilepsia: Implicación clínica]

Angel T. Alvarado1*, Juan Cotuá2, Maryori Delgado2, Alexis Morales3, Ana María Muñoz4, César Li Amenero5, María R. Bendezú6, Jorge A. García6, Doris Laos-Anchante6, Felipe Surco-Laos6, Berta Loja7, Mario Bolarte-Arteaga8, Mario Pineda-Pérez9

1International Research Network of Pharmacology and Precision Medicine (REDIFMEP), Human Medicine, San Ignacio de Loyola University, La Molina 15024, Lima, Peru.

2Neurology and Neurosurgery of the Sabana Neurosabana, Sincelejo 700001, Colombia.

3Department of Toxicology and Pharmacology, Faculty of Pharmacy and Bioanalysis, Universidad Los Andes, 5101, Merida, Venezuela.

4Institute of Food Science and Nutrition, ICAN, San Ignacio de Loyola University, La Molina 15024, Lima, Peru.

5Outpatient Clinic, Victor Larco Herrera Hospital, 15076, Lima, Peru.

6Faculty of Pharmacy and Biochemistry, San Luis Gonzaga National University of Ica, 11004, Ica, Peru.

7Environmental Engineering, Faculty of Engineering, San Ignacio de Loyola University, La Molina 15024, Lima, Peru.

8Human Medicine, Continental University, Los Olivos 15304, Lima, Peru.

9Pharmacy and Biochemistry, Faculty of Health Sciences, Scientific University of the South, UCSUR, 15067, Lima, Peru.

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

Abstract

Context: Therapeutic drug monitoring (TDM) allows personalizing the dose of valproic acid in patients with epilepsy to optimize drug therapy, minimize adverse effects and detect interactions.

Aims: To determine valproic acid concentrations in serum samples from people with epilepsy and to analyze its clinical implications.

Methods: Cloned donor enzyme immunoassay; descriptive, cross-sectional, non-randomized, convenience recruitment study of 57 voluntary patients with epilepsy (n = 39 male, 68.42%; n = 18 female, 31.58%) aged between 19 and 62 years. After three months of treatment with valproic acid, a single blood sample was collected from each volunteer at a minimal concentration.

Results: Serum drug concentrations 51.30-100.10 mg/L (SD 5.94) and level/dose 2.17-5.31 (SD 1.14) were observed. Association was shown between the dose ratio/dose of valproic acid (R2 = 0.8693; p<0.05) and the Mann-Whitney U test (p<0.05). Valproic acid monotherapy and association with carbamazepine and phenytoin are not different between treatment groups (Mann-Whitney U test: p = 0.391 > α = 0.05).

Conclusions: Serum valproic acid concentrations are within the therapeutic range, and there is a significant inverse linear correlation between dose ratio/dose, which must be considered to personalize the dose and optimize the pharmacotherapeutic result.

Keywords: dose-dose relationship; epilepsy; serum concentration; therapeutic monitoring; valproic acid.

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Resumen

Contexto: La monitorización terapéutica del fármaco (TDM) permite personalizar la dosis de ácido valproico en pacientes con epilepsia, para optimizar la terapia farmacológica, minimizar los efectos adversos y detectar interacciones.

Objetivos: Determinar las concentraciones de ácido valproico en muestras de suero de personas con epilepsia, y analizar su implicancia clínica.

Métodos: Inmunoensayo de enzima donante clonada; estudio descriptivo, transversal, reclutamiento por conveniencia y no aleatorizado de 57 pacientes voluntarios con epilepsia (n = 39 masculinos, 68,42%; n =18 femenino, 31,58%) edad entre 19 y 62 años. Después de tres meses de tratamiento con ácido valproico, se colectó una sola muestra de sangre de cada voluntario a concentración mínima.

Resultados: Se observó concentraciones de fármaco en suero 51,30-100,10 mg/L (SD 5,94), nivel/dosis 2,17-5,31 (SD 1,14). Se mostró asociación entre relación dosis/dosis de ácido valproico (R2 = 0,8693; p<0,05), y Prueba U de Mann-Whitney (p<0,05). Monoterapia de ácido valproico y asociación con carbamazepina y fenitoína no son diferentes entre los grupos de tratamiento (Prueba U de Mann-Whitney: p = 0,391 > α = 0,05).

Conclusiones: Las concentraciones de ácido valproico en suero se encuentra dentro del intervalo terapéutico y existe una correlación lineal inversa significativa entre relación dosis/dosis, que se deben considerar para personalizar la dosis, y optimizar el resultado farmacoterapéutico.

Palabras Clave: ácido valproico; concentración sérica; relación dosis-dosis; epilepsia; seguimiento terapéutico.

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Citation Format: Alvarado AT, Cotuá J, Delgado M, Morales A, Muñoz AM, Li C, Bendezú MR, García JA, Laos-Anchante D, Surco-Laos F, Loja B, Bolarte-Arteaga M, Pineda-Pérez M (2022) Serum concentrations of valproic acid in people with epilepsy: Clinical implication. J Pharm Pharmacogn Res 10(6): 1117–1125. https://doi.org/10.56499/jppres22.1500_10.6.1117
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© 2022 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Phyllanthus tenellus and Kaempferia parviflora compounds inhibit SARS-CoV-2

Pharmaceutical Science, , , , , , ,

J. Pharm. Pharmacogn. Res., vol. 10, no. 6, pp. 1103-1116, November-December 2022.

DOI: https://doi.org/10.56499/jppres22.1485_10.6.1103

Original Article

Phyllanthus tenellus Roxb. and Kaempferia parviflora Wall. ex Baker compounds as inhibitors of SARS-CoV-2 main protease and RNA-dependent RNA polymerase: A molecular docking study

[Compuestos de Phyllanthus tenellus Roxb. y Kaempferia parviflora Wall. ex Baker como inhibidores de la proteasa principal del SARS-CoV-2 y de la ARN polimerasa dependiente de ARN: Un estudio de acoplamiento molecular]

Suhaina Supian*, Muhamad Aizuddin Ahmad, Lina Rozano, Machap Chandradevan, Zuraida Ab Rahman

Biotechnology and Nanotechnology Research Centre, Malaysian Agricultural Research and Development Institute (MARDI), Serdang 43400, Selangor, Malaysia.

*E-mail: suhaina@mardi.gov.my

Abstract

Context: The outbreak of a novel coronavirus, SARS-CoV-2 has caused an unprecedented COVID-19 pandemic. To put an end to this pandemic, effective antivirals should be identified or developed for COVID-19 treatment. However, specific and effective antivirals or inhibitors against SARS-CoV-2 are still lacking.

Aims: To evaluate bioactive compounds from Phyllanthus tenellus and Kaempferia parviflora as inhibitorsagainst two essential SARS-CoV-2 proteins, main protease (Mpro) and RNA-dependent RNA polymerase (RdRp), through molecular docking studies and to predict the drug-likeness properties of the compounds.

Methods: The inhibition potential and interaction of P. tenellus and K. parviflora compounds against Mpro and RdRp were assessed through molecular docking. The drug-likeness properties of the compounds were predicted using SwissADME and AdmetSAR tools.

Results: Rutin and ellagic acid glucoside from P. tenellus and 4-hydroxy-6-methoxyflavone and 5-hydroxy-3,7,4’-trimethoxyflavone from K. parviflora exhibited the highest binding conformations to Mpro by interacting with its substrate binding site that was predicted to halt the Mpro activity. As for RdRp, ellagitannin and rutin from P. tenellus and peonidin and 5,3’-dihydroxy-3,7,4’-trimethoxyflavone from K. parviflora were the best-docked compounds that bound to the RdRp catalytic domain (Asp760 and Asp761) and NTP-entry channel that were anticipated to stop RNA polymerization. However, in the context of drug developability, 4-hydroxy-6-methoxyflavone, 5-hydroxy-3,7,4’-trimethoxyflavone, peonidin and 5,3’-dihydroxy-3,7,4’-trimethoxyflavone from K. parviflora were highly potential to be oral active drugs compared to rutin, ellagic acid glucoside and ellagitannin from P. tenellus.

Conclusions: P. tenellus and K. parviflora compounds, particularly the aforementioned compounds, were suggested as potential inhibitors of SARS-CoV-2 Mpro and RdRp.

Keywords: antiviral; compounds; COVID-19; in silico; Kaempferia parviflora; Phyllanthus tenellus.

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Resumen

Contexto: El brote de un nuevo coronavirus, el SARS-CoV-2, ha provocado una pandemia de COVID-19 sin precedentes. Para poner fin a esta pandemia, es necesario identificar o desarrollar antivirales eficaces para el tratamiento del COVID-19. Sin embargo, aún se carece de antivirales o inhibidores específicos y eficaces contra el SARS-CoV-2.

Objetivos: Evaluar compuestos bioactivos de Phyllanthus tenellus y Kaempferia parviflora como inhibidores contra dos proteínas esenciales del SARS-CoV-2, la proteasa principal (Mpro) y la ARN polimerasa dependiente del ARN (RdRp), mediante estudios de acoplamiento molecular y predecir las propiedades de similitud con los fármacos de los compuestos.

Métodos: El potencial de inhibición y la interacción de los compuestos de P. tenellus y K. parviflora contra la Mpro y la RdRp fueron evaluados mediante docking molecular. Las propiedades de semejanza de los compuestos se predijeron mediante las herramientas SwissADME y AdmetSAR.

Resultados: La rutina y el glucósido del ácido elágico de P. tenellus y la 4-hidroxi-6-metoxiflavona y la 5-hidroxi-3,7,4′-trimetoxiflavona de K. parviflora mostraron las conformaciones de unión más altas a Mpro al interactuar con su sitio de unión al sustrato que se predijo para detener la actividad de Mpro. En cuanto a la RdRp, la elagitanina y la rutina de P. tenellus y la peonidina y la 5,3′-dihidroxi-3,7,4′-trimetoxiflavona de K. parviflora fueron los compuestos mejor acoplados que se unieron al dominio catalítico de la RdRp (Asp760 y Asp761) y al canal de entrada NTP que se anticipó que detendría la polimerización del ARN. Sin embargo, en el contexto del desarrollo de fármacos, la 4-hidroxi-6-metoxiflavona, la 5-hidroxi-3,7,4′-trimetoxiflavona, la peonidina y la 5,3′-dihidroxi-3,7,4′-trimetoxiflavona de K. parviflora tendrían un gran potencial para ser fármacos activos por vía oral en comparación con la rutina, el glucósido de ácido elágico y la elagitanina de P. tenellus.

Conclusiones: Los compuestos de P. tenellus y K. parviflora, en particular los mencionados, fueron sugeridos como potenciales inhibidores de Mpro y RdRp del SARS-CoV-2.

Palabras Clave: antiviral; compuestos; COVID-19; in silico; Kaempferia parviflora; Phyllanthus tenellus.

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Citation Format: Supian S, Ahmad MA, Rozano L, Chandradevan M, Ab Rahman Z (2022) Phyllanthus tenellus Roxb. and Kaempferia parviflora Wall. ex Baker compounds as inhibitors of SARS-CoV-2 main protease and RNA-dependent RNA polymerase: A molecular docking study. J Pharm Pharmacogn Res 10(6): 1103–1116. https://doi.org/10.56499/jppres22.1485_10.6.1103
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© 2022 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Stachytarpheta jamaicensis antibacterial activity

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J. Pharm. Pharmacogn. Res., vol. 10, no. 6, pp. 1087-1102, November-December 2022.

DOI: https://doi.org/10.56499/jppres22.1474_10.6.1087

Original Article

Antibacterial activity of Stachytarpheta jamaicensis (L.) Vahl roots extract on some bacteria proteins: An in silico and in vitro study

[Actividad antibacteriana del extracto de raíces de Stachytarpheta jamaicensis (L.) Vahl sobre algunas proteínas bacterianas: un estudio in silico e in vitro]

Juliyatin Putri Utami1*, Sherli Diana2, Rahmad Arifin3, Irham Taufiqurrahman4, Kholifa Aulia Nugraha5, Milka Widya Sari5, Rizky Yoga Wardana5

1Department of Biomedicine, Faculty of Dentistry, University of Lambung Mangkurat, Banjarmasin, Indonesia.

 2Department of Conservative Dentistry, Faculty of Dentistry, University of Lambung Mangkurat, Banjarmasin, Indonesia.

3Department of Prosthodontic, Faculty of Dentistry, University of Lambung Mangkurat, Banjarmasin, Indonesia.

4Departement of Oral Maxillofacial Surgery, Faculty of Dentistry, University of Lambung Mangkurat, Banjarmasin, Indonesia.

5Undergraduate of Dentistry Program, Faculty of Dentistry, University of Lambung Mangkurat, Banjarmasin, Indonesia.

*E-mail: juliyatin.utami@ulm.ac.id

Abstract

Context: Stachytarpheta jamaicensis (L.) Vahlplant is used for traditional therapy because of its content, including flavonoids, alkaloids, tannins, saponins, terpenoids, and coumarins.

Aims: To determine the antibacterial ability of S. jamaicensis roots extract (SJRE) on some selected mouth bacteria through in vitro and in silico studies.

Methods: Phytochemical analysis and liquid chromatography-high resolution mass spectrometry (LC-HRMS) were done to explore the active compounds on SJRE. Absorption, distribution, metabolism, excretion and toxicity prediction, molecular docking simulation and visualization of luvangetin, and xanthyletin as anti-inflammatory and antibacterial were investigated in silico. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of SJRE against Aggregatibacter actinomycetemcomitans, Enterococcus faecalis, and Actinomyces spp. were calculated.

Results: Luvangetin and xanthyletin are good candidate drug molecules with low toxicity. Xanthyletin has higher binding activity than luvangetin to TNF-α, IL-6, IL-10, peptidoglycan, flagellin, and dectin protein. SJRE exhibited a high antibacterial ability, and MIC. This extract inhibits the growth of A. actinomycetemcomitans, E. faecalis and Actinomyces spp. at various concentrations 2000, 8000, and 8000 µg/mL, respectively, with statistically significant differences (p = 0.0001; p<0.05).

Conclusions: SJRE has an antibacterial ability, and 2000 µg/mL SJRE may act as an antibacterial agent in vitro. In addition, xanthyletin in SJRE has a potential role as an antibacterial and anti-inflammatory in silico.

Keywords: communicable disease; dentistry; infectious disease; medicine; periodontal disease.

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Resumen

Contexto: La planta de Stachytarpheta jamaicensis (L.) Vahl se utiliza para la terapia tradicional por su contenido, que incluye flavonoides, alcaloides, taninos, saponinas, terpenoides y cumarinas.

Objetivos: Determinar la capacidad antibacteriana del extracto de raíces de S. jamaicensis (SJRE) sobre algunas bacterias bucales seleccionadas mediante estudios in vitro e in silico.

Métodos: Se realizaron análisis fitoquímico y cromatografía líquida-espectrometría de masas de alta resolución (LC-HRMS) para explorar los compuestos activos en SJRE. Se investigaron in silico la absorción, la distribución, el metabolismo, la excreción y la predicción de la toxicidad, la simulación de acoplamiento molecular y la visualización de la luvangetina y la xantiletina como antiinflamatorios y antibacterianos. Se calcularon la concentración inhibitoria mínima (MIC) y la concentración bactericida mínima (MBC) de SJRE contra Aggregatibacter actinomycetemcomitans, Enterococcus faecalis y Actinomyces spp.

Resultados: Luvangetin y xanthyletin son buenas moléculas candidatos a fármacos y tienen baja toxicidad. La xantiletina tiene una mayor actividad de unión que la luvangetina a TNF-α, IL-6, IL-10, peptidoglicano, flagelina y proteína dectina. SJRE exhibió una alta capacidad antibacteriana y MIC. Este extracto inhibe el crecimiento de A. actinomycetemcomitans, E. faecalis y Actinomyces spp. a varias concentraciones 2000, 8000 y 8000 µg/mL, respectivamente, con diferencias estadísticamente significativas (p = 0,0001; p<0,05).

Conclusiones: SJRE tiene una capacidad antibacteriana y a 2000 µg/mL SJRE puede actuar como un agente antibacteriano in vitro. Además, la xantiletina en SJRE tiene un papel potencial como antibacteriano y antiinflamatorio in silico.

Palabras Clave: enfermedad infecciosa; enfermedad periodontal; enfermedad transmisible; odontología; medicamento.

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Citation Format: Utami JP, Diana S, Arifin R, Taufiqurrahman I, Nugraha KA, Sari MW, Wardana RY (2022) Antibacterial activity of Stachytarpheta jamaicensis (L.) Vahl roots extract on some bacteria proteins: An in silico and in vitro study. J Pharm Pharmacogn Res 10(6): 1087–1102. https://doi.org/10.56499/jppres22.1474_10.6.1087
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Rhodomyrtus tomentosa and HIF1α-VEGF expressions in placental

Pharmaceutical Science, , , , , , ,

J. Pharm. Pharmacogn. Res., vol. 10, no. 6, pp. 1076-1086, November-December 2022.

DOI: https://doi.org/10.56499/jppres22.1517_10.6.1076

Original Article

Effect of Rhodomyrtus tomentosa Hassk. on HIF1α and VEGF expressions on hypertension placental

[Efecto de Rhodomyrtus tomentosa Hassk. sobre las expresiones de HIF1α y VEGF sobre la hipertensión placentaria]

Putri Cahaya Situmorang1*, Syafruddin Ilyas1, Doni Aldo Samuel Siahaan1, Martina Restuati2, Endang Ratna Sari1, Chairunisa Chairunisa1, Muhammad Faldhy Maliki1

1Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Sumatera Utara, Medan, Indonesia.

2Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Negeri Medan, Medan, Indonesia.

*E-mail: putri.cahaya@usu.ac.id

Abstract

Context: HIF1α and VEGF are proteins marker oxidative stress and a decrease in placental growth factor (PlGF). Decreasing of HIF1α and VEGF in rats displayed poor trophoblast differentiation, placental abnormalities, and fetal mortality. Rhodomyrtus tomentosa is a flowering plant in the Myrtaceae family that has the potential to be a source of health-promoting chemicals.

Aims: To analyze HIF1α and VEGF in serum and hypertension placental tissue after giving Rhodomyrtus tomentosa (RHO) leaves extract.

Methods: Six treatments were given to the rats that were identified as being pregnant and pregnant rats with hypertension were given RHO with three doses: (a) normal pregnant rats (control); (b) hypertensive rats; (c) hypertensive rats + 100 mg/kg BW of RHO; (d) hypertensive rats +200 mg/kg BW of RHO; and (e) hypertensive rats + 400 mg/kg BW of RHO and (f) hypertensive rats + nifedipine. Under ketamine anesthesia, pregnant rats were removed on their 20th day of gestation. Immunohistochemistry and ELISA were used to assess HIF1α and VEGF protein expression.

Results: There was a significant difference (p<0.01) in the expression of HIF1α and VEGF in the labyrinthine zone and yolk sac of the rat placenta between the normal (C-) and hypertensive (C+) groups. HIF1α and VEGF expression decreased when RHO was administered at doses ranging from 100 to 400 mg/kg BW. However, there was no significant change (p>0.05) in VEGF expression in the basal zone of the rat placenta across all groups.

Conclusions: Rhodomyrtus tomentosa leaves extract decreases HIF1α and VEGF expressions in serum and repairs the tissue of the placenta’s labyrinth, basal, and yolk sacs.

Keywords: basal zone; HIF1α; hypertension; labyrinth zone; plant extract; VEGF; yolk sac.

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Resumen

Contexto: HIF1α y VEGF son proteínas marcadoras de estrés oxidativo y disminución del factor de crecimiento placentario (PlGF). La disminución de HIF1α y VEGF en ratas mostró una pobre diferenciación del trofoblasto, anomalías placentarias y mortalidad fetal. Rhodomyrtus tomentosa es una planta con flores de la familia Myrtaceae que tiene el potencial de ser una fuente de productos químicos que promueven la salud.

Objetivos: Analizar HIF1α y VEGF en suero y tejido placentario hipertenso después de administrar extracto de hojas de Rhodomyrtus tomentosa (RHO).

Métodos: Se administraron seis tratamientos a las ratas que se identificaron como preñadas ya las ratas preñadas con hipertensión se les administró RHO con tres dosis: (a) ratas preñadas normales (control); (b) ratas hipertensas; (c) ratas hipertensas + 100 mg/kg de peso corporal de RHO; (d) ratas hipertensas +200 mg/kg de peso corporal de RHO; y (e) ratas hipertensas + 400 mg/kg de peso corporal de RHO y (f) ratas hipertensas + nifedipina. Bajo anestesia con ketamina, las ratas preñadas se extrajeron en su día 20 de gestación. Se usaron inmunohistoquímica y ELISA para evaluar la expresión de proteínas HIF1α y VEGF.

Resultados: Hubo diferencia significativa (p<0.01) en la expresión de HIF1α y VEGF en la zona laberíntica y saco vitelino de la placenta de rata entre los grupos normal (C-) e hipertenso (C+). La expresión de HIF1α y VEGF disminuyó cuando se administró RHO en dosis que oscilaron entre 100 y 400 mg/kg de peso corporal. Sin embargo, no hubo cambios significativos (p>0,05) en la expresión de VEGF en la zona basal de la placenta de rata en todos los grupos.

Conclusiones: El extracto de hojas de Rhodomyrtus tomentosa disminuye las expresiones de HIF1α y VEGF en suero y repara el tejido del laberinto, basal y saco vitelino de la placenta.

Palabras Clave: extracto de plantas; HIF1α; hipertensión; saco vitelino; VEGF; zona basal; zona laberinto.

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Citation Format: Situmorang PC, Ilyas S, Siahaan DAS, Restuati M, Sari ER, Chairunisa C, Maliki MF (2022) Effect of Rhodomyrtus tomentosa Hassk. on HIF1α and VEGF expressions on hypertension placental. J Pharm Pharmacogn Res 10(6): 1076–1086. https://doi.org/10.56499/jppres22.1517_10.6.1076
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© 2022 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Validation of questionnaires to measure educational needs about medications

Pharmaceutical Science, , , , , ,

J. Pharm. Pharmacogn. Res., vol. 10, no. 6, pp. 1058-1075, November-December 2022.

DOI: https://doi.org/10.56499/jppres22.1515_10.6.1058

Original Article

Design and validation of questionnaires to measure educational needs about medications in students, parents, and teachers in an elementary school

[Diseño y validación de cuestionarios para medir necesidades educativas sobre medicamentos en alumnos, padres y profesores en una escuela primaria]

Ana M. Téllez-López1, Brenda Y. Márquez Castro2, Isis Beatriz Bermudez-Camps2, Ivette Reyes Hernández2, Maricela López Orozco2, Leobardo Manuel Gómez-Oliván1*

1Laboratorio de Toxicología Ambiental, Facultad de Química, Universidad Autónoma del Estado de México. Paseo Colón intersección Paseo Tollocan, Colonia Residencial Colón, CP 50120, Toluca, Estado de México.

2Área Académica de Farmacia. Instituto de Ciencias de la Salud. Universidad Autónoma del Estado de Hidalgo. Circuito Ex Hacienda La Concepción S/N Carretera Pachuca-Actopan. CP 42160, San Agustín Tlaxiaca, Hidalgo. México.

*E-mail: lmgomezo@uaemex.mx

Abstract

Context: To achieve a health literacy program aimed at improving the use of medicines, it is necessary to have tools that identify educational needs through valid and reliable instruments.

Aims: To validate instruments designed to evaluate the correct use of medicines in an elementary school in the state of Hidalgo, Mexico, applying the Delphi method.

Methods: A descriptive, mixed study was carried out. Three questionnaires were designed based on a documentary analysis and the identification of influential variables expressed in dimensions and items, such as sociodemographic, pharmacotherapeutic, and clinical characteristics. The content validity was determined by applying the Delphi method, the mathematical model of Torgerson (MMT), and Aiken’s v coefficient, while the internal reliability was determined by Cronbach’s alpha value and the interobserver concordance by the Kappa index.

Results: Three questionnaires were designed with 33, 48, and 44 items addressed to students, parents, and teachers respectively. The content was valid meeting the MMT criteria and Aiken’s v values above 0.9. Reliability was moderate with Cronbach’s alpha values of 0.6 and inter-observer agreement was moderate with Kappa index values of 0.4. Reliability and concordance values are accepted when considering the literature review and rigorous expert input.

Conclusions: The designed questionnaires contain valid and reliable items that will allow obtaining the necessary information to build an education program of medication use in an elementary school considering the integration of students, parents, and teachers.

Keywords: health literacy; knowledge; medicines; questionnaires; rational use medicines; validation.

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Resumen

Contexto: Para lograr un programa de alfabetización en salud dirigido a mejorar el uso de los medicamentos es necesario disponer de herramientas que identifiquen las necesidades educativas a través de instrumentos válidos y fiables.

Objetivos: Validar instrumentos diseñados para evaluar el uso correcto de los medicamentos en una escuela primaria del estado de Hidalgo, México, aplicando el método Delphi.

Métodos: Se realizó un estudio descriptivo, mixto. Se diseñaron tres cuestionarios a partir de un análisis documental y la identificación de variables de influencia expresadas en dimensiones e ítems, tales como características sociodemográficas, farmacoterapéuticas y clínicas. La validez de contenido se determinó aplicando el método Delphi, el modelo matemático de Tórgerson (MMT) y el coeficiente v de Aiken; en tanto que la confiabilidad interna a través del valor de alfa de Cronbach y la concordancia interobservadores por el índice Kappa.

Resultados: Se diseñaron tres cuestionarios con 33, 48 y 44 ítems dirigidos a alumnos, padres y profesores respectivamente. El contenido fue válido cumpliendo los criterios del MMT y valores de v de Aiken superiores a 0.9. La fiabilidad fue moderada con valores de alfa de Cronbach de 0.6 y la concordancia entre observadores moderada con valores de índice Kappa de 0.4. Se aceptan los valores de fiabilidad y concordancia al considerar la revisión bibliográfica y las aportaciones rigurosas de los expertos.

Conclusiones: Los cuestionarios diseñados contienen ítems válidos y fiables que permitirán obtener la información necesaria para construir un programa de educación del uso de medicamentos en una escuela primaria considerando la integración de alumnos, padres y profesores.

Palabras Clave: alfabetización en salud; conocimiento; cuestionarios; uso racional de medicamentos; validación.

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Citation Format: Téllez AM, Márquez BY, Bermúdez IB, Reyes I, López M, Gómez LM (2022) Design and validation of questionnaires to measure educational needs about medications in students, parents, and teachers in an elementary school. J Pharm Pharmacogn Res 10(6): 1058–1075. https://doi.org/10.56499/jppres22.1515_10.6.1058
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© 2022 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Epitope prediction of candoxin protein from Malayan krait

Pharmaceutical Science, , , ,

J. Pharm. Pharmacogn. Res., vol. 10, no. 6, pp. 1046-1057, November-December 2022.

DOI: https://doi.org/10.56499/jppres22.1469_10.6.1046

Original Article

Virtual prediction of potential immunogenic epitope of candoxin protein from Malayan krait (Bungarus candidus) venom

[Predicción virtual del epítopo inmunogénico potencial de la proteína candoxina del veneno de krait malayo (Bungarus candidus)]

Rahmat Grahadi1,2, Fatchiyah Fatchiyah1,2, Nia Kurniawan1*

1Department of Biology, Faculty of Mathematics and Natural Sciences, Brawijaya University, Jl. Veteran, 65145, Malang, Indonesia.

2Research Center of Smart Molecules of Natural Genetic Resources (SMONAGENES), Brawijaya University, Malang, Indonesia.

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

Abstract

Context: Malayan krait (Bungarus candidus) is a snake that is considered highly venomous snake and widely distributed across Southeast Asia. Envenomation by this snake is characterized by facial weakness, paralysis, respiratory muscle weakness, and in most cases, it renders the victim dead. Unfortunately, there is only one antivenom for neutralizing venom that is only available from the Thai Red Cross Society.

Aims: To predict the epitopes from candoxin protein of B. candidus venom that could be a candidate for vaccine-based antivenom.

Methods: :  In this study, IEDB and SYFPHEITHI databases were utilized to predict candoxin epitope sequences and determine their immunogenicity, conservancy, and population coverage. Next, the epitopes were modeled, and the binding interactions between epitopes and MHC-II were analyzed. The epitope that binds into the active site of human and murine MHC-II proceeded to the next step. Then, the allergenic properties of the chosen epitope were assessed to ensure its safety. Lastly, the physicochemical characteristics prediction and molecular dynamics simulation were conducted to verify the epitope’s stability when produced in vivo.

Results: The results showed that epitope 47-CFKESWREARGTRIE-61 has the best binding interaction when compared to others. This epitope was confirmed that did not show potential allergenic properties. The physicochemical properties and molecular dynamics simulation demonstrated that this epitope was stable.

Conclusions: The results of this study will be useful in developing a novel antivenom for Bungarus candidus using a vaccine-based method.

Keywords: animal toxin; antivenom; neurotoxin; vaccine.

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Resumen

Contexto: La krait malaya (Bungarus candidus) es una serpiente que se considera altamente venenosa y está ampliamente distribuida en el sudeste asiático. El envenenamiento por esta serpiente se caracteriza por debilidad facial, parálisis, debilidad de los músculos respiratorios y, en la mayoría de los casos, provoca la muerte de la víctima. Desafortunadamente, solo hay un antiveneno para neutralizar el veneno que solo está disponible en la Sociedad de la Cruz Roja Tailandesa.

Objetivos: Predecir los epítopos de la proteína candoxina del veneno de B. candidus que podrían ser candidatos a antiveneno vacunal.

Métodos: En este estudio, se utilizaron las bases de datos IEDB y SYFPHEITHI para predecir las secuencias de epítopos de candoxina y determinar su inmunogenicidad, conservación y cobertura poblacional. A continuación, se modelaron los epítopos y se analizaron las interacciones de unión entre los epítopos y el MHC-II. El epítopo que se une al sitio activo del MHC-II humano y murino pasó al siguiente paso. Luego, se evaluaron las propiedades alergénicas del epítopo elegido para garantizar su seguridad. Por último, se realizó la predicción de las características fisicoquímicas y la simulación de la dinámica molecular para verificar la estabilidad del epítopo cuando se produce in vivo.

Resultados: Los resultados mostraron que el epítopo 47-CFKESWREARGTRIE-61 tiene la mejor interacción de unión en comparación con otros. Se confirmó que este epítopo no presentaba propiedades alergénicas potenciales. La simulación de propiedades fisicoquímicas y dinámica molecular demostró que este epítopo era estable.

Conclusiones: Los resultados de este estudio serán útiles para desarrollar un nuevo antiveneno para Bungarus candidus utilizando un método basado en vacunas.

Palabras Clave: antiveneno; neurotoxina; toxina animal; vacuna.

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Citation Format: Grahadi R, Fatchiyah F, Kurniawan N (2022) Virtual prediction of potential immunogenic epitope of candoxin protein from Malayan krait (Bungarus candidus) venom. J Pharm Pharmacogn Res 10(6): 1046–1057. https://doi.org/10.56499/jppres22.1469_10.6.1046
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TNF-alpha and NF-kB expressions during OTM post-administration of CAPE

Pharmaceutical Science, , , , ,

J. Pharm. Pharmacogn. Res., vol. 10, no. 6, pp. 1037-1045, November-December 2022.

DOI: https://doi.org/10.56499/jppres22.1479_10.6.1037

Original Article

Anti-inflammatory effect of caffeic acid phenethyl ester supplementation on TNF-α and NF-κB expressions throughout experimental tooth movement in vivo

[Efecto antiinflamatorio de la suplementación con éster fenetílico de ácido cafeico en las expresiones de TNF-α y NF-κB a través del movimiento dental experimental in vivo]

Kirana Salikha1, Ida Bagus Narmada1*, Alida1, Alexander Patera Nugraha1,2, Annisa Fitria Sari2, Wibi Riawan3, Tengku Natasha Eleena Binti Tengku Ahmad Noor4

1Department of Orthodontics, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia.

2Graduate Student of Dental Health Science, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia.

3Biomolecular Biochemistry, Faculty of Medicine, Universitas Brawijaya, Malang, Indonesia.

4Membership of Faculty of Dental Surgery, Royal College of Surgeon, Edinburgh University, United Kingdom.

*E-mail: ida-b-n@fkg.unair.ac.id

Abstract

Context: Orthodontic tooth movement (OTM) changes the periodontal tissue and increases the incidence of root resorption (OIRR). Caffeic acid phenethyl ester (CAPE), an antioxidant and anti-inflammatory chemical generated from honey propolis, might be useful in controlling inflammation during OTM and so reducing the risk of OIRR.

Aims: To evaluate if CAPE supplementation has an anti-inflammatory impact on tumor necrosis factor-α (TNF-α) and nuclear transcription factor κB (NF-κB) during experimental OTM in male Wistar rats (Rattus novergicus).

Methods: Forty-eight healthy male Wistar rats were divided into positive control group (OTM 10 g/mm2 force application) and experimental group (OTM application and CAPE administration). Each groups were observed for 3, 7, 14 days. A nickel-titanium closed coil spring that was 8.0 mm long, thick was inserted between the upper left first molar and upper central incisor in order to move the molar mesially. A 20 mg/kg body weight dose of CAPE was taken orally. Using immunohistochemistry, the expression of TNF-α and NF-κB was examined on the compression side of the OTM. Both the Tukey’s honest significant difference test and the one-way analysis of variance test were applied (p<0.05).

Results: TNF-α and NF-κB expression in the compression side differed considerably across groups (p<0.05). Daily administration of CAPE significantly downregulates TNF-α and NF-κB expression on the compression side.

Conclusions: Administration of CAPE throughout OTM can successfully reduce the number of TNF-α and NF-κB expressions in the compression side in vivo.

Keywords: caffeic acid phenethyl ester; experimental tooth movement; medicine; nuclear transcription factor-κB; tumor necrosis factor-α.

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Resumen

Contexto: El movimiento dental ortodóncico (OTM) cambia el tejido periodontal y aumenta la incidencia de reabsorción radicular (OIRR). El éster fenetílico del ácido cafeico (CAPE), un químico antioxidante y antiinflamatorio generado a partir del propóleo de la miel, podría ser útil para controlar la inflamación durante la OTM y así reducir el riesgo de OIRR.

Objetivos: Evaluar si la suplementación con CAPE tiene un impacto antiinflamatorio sobre el factor de necrosis tumoral-α (TNF-α) y el factor de transcripción nuclear κB (NF-κB) durante OTM experimental en ratas Wistar macho (Rattus novergicus).

Métodos: Cuarenta y ocho ratas Wistar macho sanas se dividieron en un grupo de control positivo (aplicación de fuerza de 10 g/mm2 de OTM) y un grupo experimental (aplicación de OTM y administración de CAPE). Cada grupo se observó durante 3, 7, 14 días. Se insertó un resorte helicoidal cerrado de níquel-titanio de 8,0 mm de largo y espesor entre el primer molar superior izquierdo y el incisivo central superior para mover el molar mesialmente. Se tomó por vía oral una dosis de 20 mg/kg de peso corporal de CAPE. Usando inmunohistoquímica, se examinó la expresión de TNF-α y NF-κB en el lado de compresión del OTM. Se aplicaron tanto la prueba de diferencia significativa honesta de Tukey como la prueba de análisis de varianza de una vía (p<0,05).

Resultados: La expresión de TNF-α y NF-κB en el lado de compresión difirió considerablemente entre los grupos (p<0,05). La administración diaria de CAPE reguló significativamente a la baja la expresión de TNF-α y NF-κB en el lado de la compresión.

Conclusiones: La administración de CAPE a través de OTM puede reducir con éxito las expresiones de TNF-α y NF-κB en el lado de compresión in vivo.

Palabras Clave: éster fenetílico del ácido cafeico; factor de necrosis tumoral-α; factor de transcripción nuclear-κB; medicamento; movimiento dental experimental.

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Citation Format: Salikha K, Narmada IB, Alida, Nugraha AP, Sari AF, Riawan W, Noor TNEBTA (2022) Anti-inflammatory effect of caffeic acid phenethyl ester supplementation on TNF-α and NF-κB expressions throughout experimental tooth movement in vivo. J Pharm Pharmacogn Res 10(6): 1037–1045. https://doi.org/10.56499/jppres22.1479_10.6.1037
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Pharmaceutical Science, , , , ,

J. Pharm. Pharmacogn. Res., vol. 10, no. 6, pp. 1026-1036, November-December 2022.

DOI: https://doi.org/10.56499/jppres22.1471_10.6.1026

Original Article

In vitro antioxidant properties and antimicrobial activity of the ethanolic extract of Senecio nutans Sch. Beep. (Asteraceae)

[Propiedades antioxidantes in vitro y actividad antimicrobiana del extracto etanólico de Senecio nutans Sch. Beep. (Asteraceae)]

Felipe Surco-Laos1, Jorge A. Garcia1, María R. Bendezú1, Doris Laos-Anchante1, Juan F. Panay-Centeno1, Manuel Valle-Campos1, Juan J. Palomino-Jhong1, Paulina Eliades Yarasca-Carlos2, Berta Loja3, Angel T. Alvarado4*

1Faculty of Pharmacy and Biochemistry, San Luis Gonzaga National University of Ica, 11004, Ica, Peru.

2Biological Sciences Faculty, San Luis Gonzaga National University of Ica, 11004, Ica, Peru.

3Environmental Engineering, San Ignacio de Loyola University, La Molina 15024, Lima, Peru.

4International Research Network of Pharmacology and Precision Medicine (REDIFMEP), San Ignacio de Loyola University, La Molina 15024, Lima, Peru.

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

Abstract

Context: Senecio nutans Sch. Beep. is used by the Andean population of Ayacucho-Peru as traditional medicine for various health problems.

Aims: To evaluate the antioxidant and antimicrobial activity of the ethanolic extract of leaves of S. nutans against the enteropathogen Escherichia coli and the filamentous fungus Aspergillus niger.

Methods: The antioxidant capacity of the ethanolic extract was evaluated by ABTS, DPPH, and FRAP assays; the antimicrobial activity was evaluated by the agar diffusion method, and determining the minimum inhibitory concentration (MIC), minimum bactericidal (MBC), and fungicidal concentration (MFC).

Results: Polyphenols, terpenes, and tannins were identified; the total polyphenolic content was 67.91 ± 0.29 mg GAE/g. The ethanolic extract at 20 mg/mL showed moderate antibacterial activity (79.14 ± 0.02% inhibition, MIC and MBC >400 μg/mL on E. coli), and antifungal (88.90 ± 0.17% inhibition, MIC and MCF >400 μg/mL on A. niger); radical scavenging capacity (ABTS 10.31 ± 0.09 mM TE/g; DPPH 8.28 ± 0.07 IC50 µg/mL) and iron reducing power (FRAP 17.72 ± 0.11 mM TE/g). S. nutans turned out to be a potential antimicrobial and antioxidant species associated with the presence of its bioactive components, for which further investigation is warranted.

Conclusions: The ethanolic extract of leaves S. nutans showed moderate activity against pathogenic bacteria (E. coli) and filamentous fungus (A. niger), as well as antioxidant activity in three in vitro methods.

Keywords: antimicrobial activity; chachacoma; in vitro antioxidant activity; phenolic compounds; Senecio nutans.

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Resumen

Contexto: Senecio nutans Sch. Beep. es utilizada por la población andina de Ayacucho-Perú como medicina tradicional en diversos problemas de salud.

Objetivos: Evaluar la actividad antioxidante y antimicrobiana del extracto etanólico de hojas de S. nutans frente al enteropatógeno Escherichia coli y el hongo filamentoso Aspergillus niger.

Métodos: La capacidad antioxidante del extracto etanólico fue evaluada mediante los ensayos de ABTS, DPPH y FRAP; la actividad antimicrobiana se evaluó mediante el método de difusión en agar, y determinando la concentración inhibitoria mínima (MIC), concentración bactericida (MBC) y fungicida mínimo (MCF).

Resultados: Se identificó polifenoles, terpenos y taninos; el contenido polifenólico total fue de 67,91 ± 0,29 mg GAE/g. El extracto etanólico a 20 mg/mL mostró actividad antibacteriana moderada (79,14 ± 0,02% de inhibición, MIC y MBC >400 μg/mL sobre E. coli), y antifúngica (88,90 ± 0,17 % de inhibición, MIC y MCF >400 μg/mL sobre A. niger); capacidad secuestradora de radicales (ABTS 10,31 ± 0,09 mM TE/g; DPPH 8,28 ± 0,07 IC50 µg/mL) y poder reductor del hierro (FRAP 17,72 ± 0,11 mM TE/g). S. nutans resultó ser una especie potencial como antimicrobiana y antioxidante, asociado a la presencia de sus componentes bioactivos, por lo que amerita mayor investigación.

Conclusiones: El extracto etanólico de las hojas de S. nutans mostró actividad moderada frente a la bacteria patógena (E. coli) y hongo filamentoso (A. niger), a la vez actividad antioxidante en tres métodos in vitro.

Palabras Clave: actividad antimicrobiana; actividad antioxidante in vitro; chachacoma; compuestos fenólicos; Senecio nutans.

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Citation Format: Surco F, García JA, Bendezú MR, Laos D, Panay JF, Valle M, Palomino JJ, Yarasca PE, Loja B, Alvarado AT (2022) In vitro antioxidant properties and antimicrobial activity of the ethanolic extract of Senecio nutans Sch. Beep. (Asteraceae). J Pharm Pharmacogn Res 10(6): 1026–1036. https://doi.org/10.56499/jppres22.1471_10.6.1026
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© 2022 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Anticancer activity of Curcuma xanthorrhiza

Pharmaceutical Science, , , ,

J. Pharm. Pharmacogn. Res., vol. 10, no. 6, pp. 1015-1025, November-December 2022.

DOI: https://doi.org/10.56499/jppres22.1448_10.6.1015

Original Article

Potential of Curcuma xanthorrhiza ethanol extract in inhibiting the growth of T47D breast cancer cell line: In vitro and bioinformatic approach

[Potencial del extracto de etanol de Curcuma xanthorrhiza para inhibir el crecimiento de la línea celular de cáncer de mama T47D: enfoque in vitro y bioinformático]

Nur Fitriana1, Muhaimin Rifa’i1, Masruri2, Septian Tri Wicaksono1, Nashi Widodo1*

1Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Brawijaya, Malang, Indonesia.

2Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Brawijaya, Malang, Indonesia.

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

Abstract

Context: Breast cancer most commonly occurs in women globally and has the highest mortality rate in Asia. Therefore, a safe and prominent drug to cure the disease needs to be urgently developed.

Aims: To investigate the molecular mechanism of the ethanol extract of Curcuma xanthorrhiza (ECx) ininducing apoptosis in breast cancer cell line T47D.

Methods: The research was started by extracting Curcuma xanthorrhiza using ethanol as solvent. The anticancer research was carried out by cell toxicity assay and apoptosis assay. This study also observed changes in cell morphology and protein expression levels that can induce cell apoptosis. The bioinformatics approach was carried out to determine the activity of the active compound in inhibiting AKT-1, which plays an important role in the development of cancer cells. TIG-1 cells were used as controls in toxicity assays.

Results: ECx showed antioxidant and nitric oxide scavenging activity, which is beneficial for human health, and exhibited selective toxicity in T47D breast cancer cells compared to TIG-1 normal cells. ECx increased the expression of p53, Bax, caspase-3, and caspase-9, which induces apoptosis. Further analysis showed that ECx contained at least eight active compounds: curcumin, curcumin II (desmethoxycurcumin), curcumene, camphor, 1,8-cineole, p-cymene, ar-turmerone, and caryophyllene oxide. Bioinformatics studies suggest that active compounds may be involved in apoptosis via the PI3K/AKT signaling pathway.

Conclusions: ECx significantly acts as an anticancer agent by inhibiting the growth of T47D cells. This research proves that the bioinformatics approach shows that curcumin can inhibit the expression of AKT-1.

Keywords: AKT1; apoptosis; bioinformatics; Curcuma xanthorrhiza.

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Resumen

Contexto: El cáncer de mama ocurre con mayor frecuencia en mujeres a nivel mundial y tiene la tasa de mortalidad más alta en Asia. Por lo tanto, es necesario desarrollar urgentemente un fármaco seguro y destacado para curar la enfermedad.

Objetivos: Investigar el mecanismo molecular del extracto etanólico de Curcuma xanthorrhiza (ECx) en la inducción de apoptosis en la línea celular de cáncer de mama T47D.

Métodos: La investigación se inició extrayendo Curcuma xanthorrhiza usando etanol como solvente. La investigación contra el cáncer se llevó a cabo mediante un ensayo de toxicidad celular y un ensayo de apoptosis. Este estudio también observó cambios en la morfología celular y los niveles de expresión de proteínas que pueden inducir la apoptosis celular. El enfoque bioinformático se llevó a cabo para determinar la actividad del compuesto activo en la inhibición de AKT-1, que juega un papel importante en el desarrollo de células cancerosas. Se usaron células TIG-1 como controles en los ensayos de toxicidad.

Resultados: ECx mostró actividad antioxidante y de eliminación de óxido nítrico, que es beneficiosa para la salud humana, y exhibió toxicidad selectiva en células de cáncer de mama T47D en comparación con células normales TIG-1. ECx aumentó la expresión de p53, Bax, caspasa-3 y caspasa-9, lo que induce la apoptosis. Un análisis posterior mostró que ECx contenía al menos ocho compuestos activos: curcumina, curcumina II (desmetoxicurcumina), curcumeno, alcanfor, 1,8-cineol, p-cimeno, ar-turmerona y óxido de cariofileno. Los estudios de bioinformática sugieren que los compuestos activos pueden estar involucrados en la apoptosis a través de la vía de señalización PI3K/AKT.

Conclusiones: ECx actúa significativamente como un agente anticancerígeno al inhibir el crecimiento de las células T47D. Esta investigación demuestra que el enfoque bioinformático muestra que la curcumina puede inhibir la expresión de AKT-1.

Palabras Clave: AKT1; apoptosis; bioinformática; Curcuma xanthorrhiza.

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Citation Format: Fitriana N, Rifa’i M, Masruri, Wicaksono ST, Widodo N (2022) Potential of Curcuma xanthorrhiza ethanol extract in inhibiting the growth of T47D breast cancer cell line: In vitro and bioinformatic approach. J Pharm Pharmacogn Res 10(6): 1015–1025. https://doi.org/10.56499/jppres22.1448_10.6.1015
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