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The Journal of Pharmacy & Pharmacognosy Research (JPPRes) is an international, specialized and peer-reviewed open access journal, which publishes studies in the pharmaceutical and herbal fields concerned with the physical, botanical, chemical, biological, toxicological properties and clinical applications of molecular entities, active pharmaceutical ingredients, devices and delivery systems for drugs, vaccines and biologicals, including their design, manufacture, evaluation and marketing. This journal publishes research papers, reviews, commentaries and letters to the editor as well as special issues and review of pre-and post-graduate thesis from pharmacists or professionals involved in Pharmaceutical Sciences or Pharmacognosy.

Ageratum conyzoides and eggshell membrane hydrolysates in chronic inflammation

J. Pharm. Pharmacogn. Res., vol. 12, no. 5, pp. 972-993, Sep-Oct 2024.


Original Article

Anti-inflammatory effect of the mixture of Ageratum conyzoides L. extract and eggshell membrane hydrolysates and in silico active compound predictions

[Efecto antiinflamatorio de la mezcla de extracto de Ageratum conyzoides L. e hidrolizados de membrana de cáscara de huevo, y predicción in silico de compuestos activos]

Suci Nar Vikasari1,3*, Elin Yulinah Sukandar3, Tri Suciati2, I Ketut Adnyana1*

1Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, Bandung Institute of Technology, Bandung, Indonesia.

2Department of Pharmaceutics, School of Pharmacy, Bandung Institute of Technology, Bandung, Indonesia.

3Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Jenderal Achmad Yani, Cimahi, Indonesia.



Context: Ageratum conyzoides L. and eggshell membrane have the potential to be used as medicine. The independent use of A. conyzoides extract or eggshell membrane hydrolysates independently as a natural medicine has been widely known, but the mixture of the two as an anti-inflammatory has not been studied.

Aims: To evaluate both the in vivo and in vitro anti-inflammatory effects of A. conyzoides extract and eggshell membrane hydrolysates, independently and in combination. In silico testing was conducted to identify chemicals that have a key role in inflammation signaling pathways.

Methods: The chronic anti-inflammatory effects of A. conyzoides extract and eggshell membrane hydrolysates were evaluated on cotton pellet-induced rats using diclofenac-Na as a control. In vitro anti-inflammatory effects were studied via protein denaturation, membrane stability, and antiprotease activity. Furthermore, molecular docking was performed on the p38-MAPK signaling pathway using compounds found in A. conyzoides extract and eggshell membrane hydrolysates.

Results: A. conyzoides extract and eggshell membrane hydrolysates given separately or in combination can inhibit the formation of exudates and granulomas. Molecular docking simulations showed that the metabolites in the extract and hydrolysate interact with p38-MAPK. Nobiletin in the extract is the potential metabolite that interacts with the p38-MAPK receptor with a free energy of binding and inhibition constant of -8.92 kcal/mol and 260.80 nM. Amino acids in the hydrolysates showed weaker interactions compared to the compound in the extract.

Conclusions: A. conyzoides extract and eggshell membrane hydrolysates work additively to inhibit the severity of chronic inflammation.

Keywords: Ageratum conyzoides; anti-inflammatory; eggshell membrane hydrolysates; molecular docking; p38-MAPK.

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Contexto: El Ageratum conyzoides L. y la membrana de cáscara de huevo tienen potencial para ser utilizados como medicamentos. El uso independiente del extracto de A. conyzoides o de los hidrolizados de membrana de cáscara de huevo como medicina natural es ampliamente conocido, pero no se ha estudiado la mezcla de ambos como antiinflamatorio.

Objetivos: Evaluar los efectos antiinflamatorios in vivo e in vitro del extracto de A. conyzoides y de los hidrolizados de membrana de cáscara de huevo, independientemente y en combinación. Se realizaron pruebas in silico para identificar sustancias químicas que desempeñan un papel clave en las vías de señalización de la inflamación.

Métodos: Se evaluaron los efectos antiinflamatorios crónicos del extracto de A. conyzoides y de los hidrolizados de membrana de cáscara de huevo en ratas inducidas por gránulos de algodón, utilizando diclofenaco-Na como control. In vitro, los efectos antiinflamatorios se estudiaron mediante la desnaturalización de proteínas, la estabilidad de la membrana y la actividad antiproteasa. Además, se realizó un acoplamiento molecular de la vía de señalización p38-MAPK utilizando compuestos presentes en el extracto de A. conyzoides y en los hidrolizados de membrana de cáscara de huevo.

Resultados: El extracto de A. conyzoides y los hidrolizados de membrana de cáscara de huevo administrados por separado o en combinación pueden inhibir la formación de exudados y granulomas. Las simulaciones de acoplamiento molecular mostraron que los metabolitos del extracto y el hidrolizado interactúan con p38-MAPK. La nobiletina del extracto es el metabolito potencial que interactúa con el receptor p38-MAPK con una energía libre de unión y una constante de inhibición de -8,92 kcal/mol y 260,80 nM. Los aminoácidos de los hidrolizados mostraron interacciones más débiles en comparación con el compuesto del extracto.

Conclusiones: El extracto de A. conyzoides y los hidrolizados de membrana de cáscara de huevo actúan de forma aditiva para inhibir la gravedad de la inflamación crónica.

Palabras Clave: acoplamiento molecular; Ageratum conyzoides; anti-inflamatorio; hidrolizados de membrana de cáscara de huevo; p38-MAPK.

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Citation Format: Vikasari SN, Sukandar EY, Suciati T, Adnyana IK (2024) Anti-inflammatory effect of the mixture of Ageratum conyzoides L. extract and eggshell membrane hydrolysates and in silico active compound predictions. J Pharm Pharmacogn Res 12(5): 972–993.

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SS-31 for diabetic nephropathy

J. Pharm. Pharmacogn. Res., vol. 12, no. 5, pp. 956-971, Sep-Oct 2024.



SS-31 protects diabetic nephropathy progression: A systematic review of in vivo and in vitro studies

[El SS-31 protege la progresión de la nefropatía diabética: Una revisión sistemática de estudios in vivo e in vitro]

Jonathan Christianto Sutadji1#, Dian Anggraini Permatasari Musalim1#, David Setyo Budi1#, Jennifer Susanto1, Fanny Gunawan1, Chaq El Chaq Zamzam Multazam2, Citrawati Dyah Kencono Wungu3,4*

1Faculty of Medicine, Universitas Airlangga, Indonesia.

2National Heart and Lung Institute, Imperial College London, London, United Kingdom.

3Department of Physiology and Medical Biochemistry, Faculty of Medicine, Universitas Airlangga, Indonesia.

4Institute of Tropical Disease, Universitas Airlangga, Indonesia.

#JCS, DAPM, and DSB are joint first authors.



Context: Diabetic nephropathy is the leading cause of end-stage renal disease and also death in the world. Administration of Szeto-Schiller-31 (SS-31) as a potential therapeutic candidate that can decrease the renal function damage progressivity in diabetes needs to be comprehensively analyzed.

Aims: To assess the protective effects of SS31 against the progressivity of diabetic nephropathy.

Methods: This systematic review follows PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) guidelines 2020. Searches of databases (Pubmed, Science Direct, Scopus, ProQuest, and Springer) were done on 17 September 2023 in order to find articles related to the animal diabetic model and SS-31 treatment. Manual searches from medRxiv were also conducted to obtain additional evidence. Renal function, histopathology analysis, reactive oxygen species in vivo, and in vitro analysis were described.

Results: There were six in vivo studies, each of which discussed the renal function, histopathology, and reactive oxygen species (ROS), and four in vitro studies that discussed ROS. The available data suggested that SS-31 improves kidney function by lowering urinary albumin excretion, proteinuria, serum creatinine, creatinine clearance, and BUN, supported by histopathological improvements. In addition, SS-31 also has the effect of lowering 8-hydroxy-2-deoxyguanosine (8-OHdG) level, malondialdehyde (MDA) level, and nicotinamide adenine dinucleotide phosphate (NADPH) expression.

Conclusions: SS31 had a renoprotective effect that could prevent the worsening of renal function in diabetic mice. In addition, the results of histopathology and ROS analysis also support the positive results of SS-31 treatment. Further studies are required to confirm its findings.

Keywords: diabetic nephropathy; elamipretide; mitochondria targeted peptide; SS-31.

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Contexto: La nefropatía diabética es la principal causa de enfermedad renal terminal y también de muerte en el mundo. Es necesario analizar exhaustivamente la administración de Szeto-Schiller-31 (SS-31) como posible candidato terapéutico capaz de disminuir la progresividad del daño de la función renal en la diabetes.

Objetivos: Evaluar los efectos protectores del SS31 contra la progresividad de la nefropatía diabética.

Métodos: Esta revisión sistemática sigue las directrices PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis) 2020. Se realizaron búsquedas en bases de datos (Pubmed, Science Direct, Scopus, ProQuest y Springer) el 17 de septiembre de 2023 para encontrar artículos relacionados con el modelo diabético animal y el tratamiento con SS-31. También se realizaron búsquedas manuales en medRxiv para obtener pruebas adicionales. Se describieron la función renal, el análisis histopatológico, las especies reactivas de oxígeno in vivo y el análisis in vitro.

Resultados: Hubo seis estudios in vivo, cada uno de los cuales analizaba la función renal, la histopatología y las especies reactivas del oxígeno (ROS), y cuatro estudios in vitro que analizaban las ROS. Los datos disponibles sugirieron que el SS-31 mejora la función renal al reducir la excreción urinaria de albúmina, la proteinuria, la creatinina sérica, el aclaramiento de creatinina y el BUN, apoyado por mejoras histopatológicas. Además, el SS-31 también tiene el efecto de reducir el nivel de 8-hidroxi-2-deoxiguanosina (8-OHdG), el nivel de malondialdehído (MDA) y la expresión de nicotinamida adenina dinucleótido fosfato (NADPH).

Conclusiones: El SS31 tuvo un efecto renoprotector que pudo prevenir el empeoramiento de la función renal en ratones diabéticos. Además, los resultados de la histopatología y el análisis de ROS también apoyan los resultados positivos del tratamiento con SS-31. Se requieren más estudios para confirmar sus resultados.

Palabras Clave: elamipretida; nefropatía diabética; péptido dirigido a las mitocondrias; SS-31.

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Citation Format: Sutadji JC, Musalim DAP, Budi DS, Susanto J, Gunawan F, Multazam CEZ, Wungu CDK (2024) SS-31 protects diabetic nephropathy progression: A systematic review of in vivo and in vitro studies. J Pharm Pharmacogn Res 12(5): 956–971.

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© 2024 Journal of Pharmacy & Pharmacognosy Research

Hypertension knowledge and its associated factors in primary care

J. Pharm. Pharmacogn. Res., vol. 12, no. 5, pp. 943-955, Sep-Oct 2024.


Original Article

Hypertension knowledge and its associated factors among hypertensive patients in primary care settings in Central Vietnam: A cross-sectional study

[Conocimiento de la hipertensión y sus factores asociados entre pacientes hipertensos en entornos de atención primaria en el centro de Vietnam: Un estudio transversal]

Ho Anh Hien1,2, Nguyen Minh Tam1, Dirk Devroey2, Stefan Heytens3, Vo Tam4, Tran Binh Thang5, Vo Nu Hong Duc5, Dang Thi Thanh Nha5, Doan Pham Phuoc Long4, Nguyen Vu Phong6, Huynh Van Minh4, Hoang Anh Tien4,6*

1Department of Family Medicine, University of Medicine and Pharmacy, Hue University, Hue, Vietnam.

2Department of Family Medicine and Chronic Care, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium.

3Department of Public Health and Primary Care, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.

4Department of Internal Medicine, University of Medicine and Pharmacy, Hue University, Hue, Vietnam.

5Faculty of Public Health, University of Medicine and Pharmacy, Hue University, Hue, Vietnam.

6Cardiovascular Center, Hue University of Medicine and Pharmacy Hospital, Hue, Vietnam.



Context: Hypertension is highly prevalent in Vietnam, yet the rate of controlled hypertension remains low. Knowledge about hypertension is linked to patient beliefs and medication adherence. However, there’s limited data on hypertension knowledge among primary care patients in Vietnam.

Aims: To evaluate the knowledge of hypertension among hypertensive patients in primary care settings in Central Vietnam and identify factors affecting their knowledge.

Methods: A cross-sectional study was conducted, and a thorough examination was performed to assess hypertension knowledge and its related factors. Utilizing the Hypertension Knowledge Level Scale and Medication Adherence Report Scale, hypertension knowledge and medication adherence were evaluated. Additionally, demographic, clinical, lifestyle, and patient belief data were gathered. Statistical analyses and logistic regression models were applied to pinpoint key factors associated with hypertension knowledge.

Results: In the study involving 761 participants (55.7% male), the average hypertension knowledge score was 15.0 (SD = 4.6), with only 45.3% demonstrating a high level of knowledge. Significant correlations were observed between hypertension knowledge and variables such as education level, ethnicity, home blood pressure monitoring, patient beliefs, and medication adherence. Logistic regression analysis indicated that higher education levels and belonging to the majority ethnicity were linked to enhanced hypertension knowledge. Notably, individuals with better hypertension knowledge tended to recognize the necessity of their prescribed medications.

Conclusions: Hypertension knowledge among primary care patients in Central Vietnam is suboptimal, with approximately half having a high knowledge level. These findings emphasize the importance of hypertension knowledge in shaping patient beliefs, perceptions, and medication adherence. Tailored educational interventions are crucial, especially for those with lower education and minority backgrounds, to enhance hypertension management.

Keywords: blood pressure; hypertension knowledge; medication adherence.

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Contexto: La hipertensión tiene una alta prevalencia en Vietnam, pero la tasa de hipertensión controlada sigue siendo baja. El conocimiento sobre la hipertensión está vinculado a las creencias del paciente y la adherencia a la medicación. Sin embargo, hay datos limitados sobre el conocimiento de la hipertensión entre los pacientes de atención primaria en Vietnam.

Objetivos: Evaluar el conocimiento sobre la hipertensión entre pacientes hipertensos en entornos de atención primaria en el centro de Vietnam e identificar factores que afectan su conocimiento.

Métodos: Se realizó un estudio transversal y un examen exhaustivo para evaluar el conocimiento sobre la hipertensión y sus factores relacionados. Utilizando la Escala de Nivel de Conocimiento sobre Hipertensión y la Escala de Informe de Adherencia a la Medicación, se evaluaron el conocimiento sobre hipertensión y la adherencia a la medicación. Además, se recopilaron datos demográficos, clínicos, de estilo de vida y de creencias de los pacientes. Se aplicaron análisis estadísticos y modelos de regresión logística para identificar factores clave asociados con el conocimiento sobre la hipertensión.

Resultados: En el estudio que involucró a 761 participantes (55,7% hombres), la puntuación promedio de conocimiento sobre hipertensión fue de 15,0 (DE = 4,6), y solo el 45,3% demostró un alto nivel de conocimiento. Se observaron correlaciones significativas entre el conocimiento sobre la hipertensión y variables como el nivel educativo, el origen étnico, el control de la presión arterial en el hogar, las creencias de los pacientes y la adherencia a la medicación. El análisis de regresión logística indicó que los niveles de educación más altos y la pertenencia a la etnia mayoritaria estaban relacionados con un mayor conocimiento sobre la hipertensión. En particular, las personas con mejores conocimientos sobre hipertensión tendían a reconocer la necesidad de los medicamentos recetados.

Conclusiones: El conocimiento sobre hipertensión entre los pacientes de atención primaria en el centro de Vietnam es subóptimo, y aproximadamente la mitad tiene un alto nivel de conocimiento. Estos hallazgos enfatizan la importancia del conocimiento sobre la hipertensión a la hora de moldear las creencias, percepciones y la adherencia a la medicación de los pacientes. Las intervenciones educativas personalizadas son cruciales, especialmente para aquellos con menor educación y antecedentes minoritarios, para mejorar el manejo de la hipertensión.

Palabras Clave: adherencia a la medicación; conocimientos sobre hipertensión; presión arterial.

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Citation Format: Hien HA, Tam NM, Devroey D, Heytens S, Tam V, Thang TB, Duc VNH, Nha DTT, Long DDP, Phong NV, Minh HV, Tien HA (2024) Hypertension knowledge and its associated factors among hypertensive patients in primary care settings in Central Vietnam: A cross-sectional study. J Pharm Pharmacogn Res 12(5): 943–955.

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© 2024 Journal of Pharmacy & Pharmacognosy Research

Molecular docking and dynamics studies of 8,9-dimethoxy ellagic acid

J. Pharm. Pharmacogn. Res., vol. 12, no. 5, pp. 929-942, Sep-Oct 2024.


Original Article

Molecular docking and dynamics studies of 8,9-dimethoxy ellagic acid contained in Peperomia pellucida (L.) Kunth against various diabetes mellitus receptors

[Estudios de acoplamiento y dinámica molecular del ácido 8,9-dimetoxielágico contenido en Peperomia pellucida (L.) Kunth frente a varios receptores de diabetes mellitus]

Yasmiwar Susilawati1,2, Raden Bayu Indradi2, Aiyi Asnawi3, Ellin Febrina4*

1Herbal Study Center, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang km. 21, Jatinangor, 45363, Indonesia.

2Department of Biology Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor 45363, Indonesia.

3Department of Pharmacochemistry, Faculty of Pharmacy, Universitas Bhakti Kencana, Jl. Soekarno-Hatta No. 754, Bandung 40617, Indonesia.

4Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang km. 21, Jatinangor 45363, Indonesia.



Context: The search for antidiabetic drugs that target the receptors involved in diabetes has received significant attention in recent years. Peperomia pellucida (L.) Kunth’s ethanol extract and ethyl acetate fraction have antihyperglycemic activity. 8,9-dimethoxy ellagic acid (DEA) has shown significant diabetes mellitus activity in mice, but its interaction with diabetes receptors remains unknown.

Aims: To perform molecular docking and molecular dynamics simulations to explore the binding interactions and stability of DEA within the binding sites of enzymes involved in diabetes.

Methods: At the outset, the utilization of molecular docking was limited to forecasting the DEA’s binding orientations and affinities within the active sites of the enzymes implicated in diabetes. Following this, molecular dynamics simulation was employed to investigate the interactions, stability, and dynamic behavior of these complexes over a period of 100 nanoseconds.

Results: Molecular docking results revealed that DEA interacts with all selected receptors involved in diabetes and interacts more strongly with the aldose reductase receptor (PDB ID 3S3G) than the native ligand, with a binding energy of -10.3 kcal/mol. However, further molecular dynamics simulations confirmed the stability of the receptor complex with DEA over 100 ns, which is less potent than that of the native ligand. This is probably due to the rigidity of the DEA molecular structure.

Conclusions: This study highlights the potential of DEA derived from P. pellucida as an inhibitor of various receptors involved in diabetes.

Keywords: 8,9-dimethoxy ellagic acid; antidiabetic; in silico; Peperomia pellucida.

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Contexto: La búsqueda de fármacos antidiabéticos que se dirijan a los receptores implicados en la diabetes ha recibido mucha atención en los últimos años. El extracto etanólico de Peperomia pellucida (L.) Kunth y la fracción de acetato de etilo tienen actividad antihiperglucemiante. El ácido 8,9-dimetoxielágico (DEA) ha mostrado una actividad significativa en la diabetes mellitus en ratones, pero su interacción con los receptores de la diabetes sigue siendo desconocida.

Objetivos: Realizar simulaciones de dinámica molecular y acoplamiento molecular para explorar las interacciones de unión y la estabilidad de la DEA dentro de los sitios de unión de las enzimas involucradas en la diabetes.

Métodos: Al principio, la utilización del acoplamiento molecular se limitaba a pronosticar las orientaciones y afinidades de unión de la DEA dentro de los sitios activos de las enzimas implicadas en la diabetes. A continuación, se empleó simulación de dinámica molecular para investigar las interacciones, la estabilidad y el comportamiento dinámico de estos complejos durante un período de 100 nanosegundos.

Resultados: Los resultados del acoplamiento molecular revelaron que la DEA interactúa con todos los receptores seleccionados implicados en la diabetes e interactúa más fuertemente con el receptor de aldosa reductasa (PDB ID 3S3G) que el ligando nativo, con una energía de unión de -10,3 kcal/mol. Sin embargo, otras simulaciones de dinámica molecular confirmaron la estabilidad del complejo del receptor con DEA durante 100 ns, que es menos potente que el del ligando nativo. Probablemente esto se deba a la rigidez de la estructura molecular de la DEA.

Conclusiones: Este estudio destaca el potencial de la DEA derivada de P. pellucida como inhibidor de diversos receptores implicados en la diabetes.

Palabras Clave: ácido 8,9-dimetoxi elágico; antidiabético; in silico; Peperomia pelucida.

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Citation Format: Susilawati Y, Indradi RB, Asnawi A, Febrina E (2024) Molecular docking and dynamics studies of 8,9-dimethoxy ellagic acid contained in Peperomia pellucida (L.) Kunth against various diabetes mellitus receptors. J Pharm Pharmacogn Res 12(5): 929–942.

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© 2024 Journal of Pharmacy & Pharmacognosy Research

Biofilms related to periodontal disease

J. Pharm. Pharmacogn. Res., vol. 12, no. 5, pp. 911-928, Sep-Oct 2024.



Research trends in the study of biofilms related to periodontal disease: A bibliometric analysis

[Tendencias de investigación en el estudio de las biopelículas relacionadas con la enfermedad periodontal: Un análisis bibliométrico]

Julio C. Romero-Gamboa1, Melissa Pinella-Vega1, Pablo A. Millones-Gómez1, John E. Gallego-Ramírez2, Alejandro Valencia-Arias3*

1Escuela de Estomatología, Universidad Señor de Sipán, Chiclayo 14001, Perú.

2Facultad de Odontología, Universidad Cooperativa de Colombia, Colombia.

3Escuela de Ingeniería Industrial, Universidad Señor de Sipán, Chiclayo 14001, Perú.



Context: The study of biofilms in the context of periodontal diseases is of paramount importance due to their central role in the pathogenesis of these oral diseases. Research has focused on understanding the formation, structure, and dynamics of biofilms, as well as developing therapeutic approaches for their eradication. However, there are still conceptual gaps in the scientific literature due to a lack of review studies.

Aims: To examine research trends in the study of biofilms related to periodontal diseases.

Methods: This study used a bibliometric analysis methodology of scientific literature based on the PRISMA-2020 statement.

Results: The results showed a remarkable increase in research activity in recent years. Prominent authors, influential journals, and emerging keywords such as “multispecies biofilm”, “biofilm formation” or “periodontal therapy” were identified, reflecting the areas of greatest interest.

Conclusions: The need to balance the exploration of new areas with the consolidation of other key concepts is highlighted, as well as gaps in research that require more precise therapeutic approaches, longitudinal studies, and greater attention to underserved communities in developing countries.

Keywords: antimicrobial therapies; biofilm; oral microbiota; pathogenesis; periodontal disease; PRISMA-2020.

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Contexto: El estudio de las biopelículas en el contexto de las enfermedades periodontales es de suma importancia debido a su papel central en la patogénesis de estas enfermedades orales. La investigación se ha centrado en la comprensión de la formación, estructura y dinámica de las biopelículas, así como en el desarrollo de enfoques terapéuticos para su erradicación. Sin embargo, todavía existen lagunas conceptuales en la literatura científica debido a la falta de estudios de revisión.

Objetivos: Examinar las tendencias de investigación en el estudio de las biopelículas relacionadas con las enfermedades periodontales.

Métodos: Este estudio utilizó una metodología de análisis bibliométrico de la literatura científica basada en la declaración PRISMA-2020.

Resultados: Los resultados mostraron un notable incremento de la actividad investigadora en los últimos años. Se identificaron autores destacados, revistas influyentes y palabras clave emergentes como “biofilm multiespecie”, “formación de biofilm” o “terapia periodontal”, que reflejan las áreas de mayor interés.

Conclusiones: Se destaca la necesidad de equilibrar la exploración de nuevas áreas con la consolidación de otros conceptos clave, así como lagunas en la investigación que requieren enfoques terapéuticos más precisos, estudios longitudinales y una mayor atención a las comunidades desatendidas de los países en desarrollo.

Palabras Clave: biopelícula; enfermedad periodontal; microbiota oral; patogénesis; PRISMA-2020; terapias antimicrobianas.

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Citation Format: Romero Gamboa JC, Pinella-Vega M, Millones-Gómez PA, Gallego-Ramírez JE, Valencia-Arias A (2024) Research trends in the study of biofilms related to periodontal disease: A bibliometric analysis. J Pharm Pharmacogn Res 12(5): 911–928.

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© 2024 Journal of Pharmacy & Pharmacognosy Research

Piceatannol-rich extract from Passiflora edulis and hyperpigmentation

J. Pharm. Pharmacogn. Res., vol. 12, no. 5, pp. 900-910, Sep-Oct 2024.


Original Article

Piceatannol-rich extract from Passiflora edulis Sims seeds attenuates morphological differentiation through the reduction of MITF mRNA expression and F-actin polymerization in UVB-induced hyperpigmented B16F10 cells

[El extracto rico en piceatannol de las semillas de Passiflora edulis Sims atenúa la diferenciación morfológica mediante la reducción de la expresión de ARNm de MITF y la polimerización de F-actina en células B16F10 hiperpigmentadas inducidas por UVB]

Paween Kunsorn1, Witchuda Payuhakrit1,2, Nasapon Povichit3, Prasit Suwannalert1,2*

1Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok, Thailand.

2Pathobiology Information and Learning Center, Department of Pathobiology, Faculty of Science, Mahidol University, Bangkok, Thailand.

3Detox (Thailand) Co., Ltd., Chiangmai, Thailand.



Context: Ultraviolet B (UVB) light irradiation causes skin problems by increasing cellular oxidants, melanogenesis, and morphological changes of melanocytes. The use of active compounds derived from plants to mitigate these problems has been studied. Piceatannol (PCT), a phytochemical in the phenolic group contained in Passiflora edulis fruit seed (PFS), has gained interest for its anti-melanogenesis effects. However, the inhibitory effect on morphological differentiation related to melanin production of PFS extract is absent.

Aims: To investigate the effect of PFS extract on the inhibition of morphological differentiation associated with microphthalmia-associated transcription factor (MITF) mRNA expression and F-actin polymerization in UVB-induced hyperpigmented B16F10 cells.

Methods: Three fractions of PFS extract were analyzed for their total phenolics, PCT proportion, and antioxidant capacity. The fraction with the highest PCT proportion and antioxidant activity was investigated for its reductive effects on cellular oxidants, number of melanin-containing cells, melanin content, MITF mRNA expression, and tyrosinase activity in UVB-induced B16F10 cells. Morphological differentiation, as well as F-actin polymerization and arrangement, were analyzed.

Results: The PFS-F3 extract showed the highest antioxidant effect related to the proportion of PCT and phenolic contents. It attenuated cellular oxidants, the number of melanin-containing cells, melanin content, MITF mRNA expression, and tyrosinase activity. Differentiation, polymerization, and the arrangement of F-actin of most UVB-irradiated cells were repressed after treatment with the extract.

Conclusions: The PFS extract rich in PCT attenuated morphological differentiation by suppressing the functions of MITF mRNA and F-actin polymerization through the reduction of cellular oxidants, resulting in a decrease in melanin production.

Keywords: F-actin polymerization; hyperpigmentation; oxidative stress; passion fruit seed; piceatannol.

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Contexto: La irradiación con luz ultravioleta B (UVB) causa problemas cutáneos al aumentar los oxidantes celulares, la melanogénesis y los cambios morfológicos de los melanocitos. Se ha estudiado el uso de compuestos activos derivados de plantas para mitigar estos problemas. El piceatannol (PCT), un fitoquímico del grupo fenólico contenido en la semilla de la fruta de Passiflora edulis (PFS), ha cobrado interés por sus efectos antimelanogénicos. Sin embargo, el efecto inhibidor sobre la diferenciación morfológica relacionada con la producción de melanina del extracto de PFS está ausente.

Objetivos: Investigar el efecto del extracto de PFS en la inhibición de la diferenciación morfológica asociada a la expresión de ARNm del factor de transcripción asociado a la microftalmia (MITF) y la polimerización de F-actina en células B16F10 hiperpigmentadas inducidas por UVB.

Métodos: Se analizaron tres fracciones de extracto de SFP para determinar sus fenólicos totales, la proporción de PCT y su capacidad antioxidante. La fracción con la mayor proporción de PCT y actividad antioxidante se investigó por sus efectos reductores sobre los oxidantes celulares, el número de células con melanina, el contenido de melanina, la expresión de ARNm de MITF y la actividad tirosinasa en células B16F10 inducidas por UVB. Se analizó la diferenciación morfológica, así como la polimerización y disposición de la F-actina.

Resultados: El extracto PFS-F3 mostró el mayor efecto antioxidante relacionado con la proporción de PCT y el contenido fenólico. Atenuó los oxidantes celulares, el número de células con melanina, el contenido de melanina, la expresión de ARNm de MITF y la actividad tirosinasa. La diferenciación, la polimerización y la disposición de la F-actina de la mayoría de las células irradiadas con UVB se reprimieron tras el tratamiento con el extracto.

Conclusiones: El extracto de PFS rico en PCT atenuó la diferenciación morfológica mediante la supresión de las funciones del ARNm de MITF y la polimerización de F-actina a través de la reducción de los oxidantes celulares, resultando en la disminución de la producción de melanina.

Palabras Clave: estrés oxidativo; hiperpigmentación; piceatannol; polimerización de F-actina; semilla de maracuyá.

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Citation Format: Kunsorn P, Payuhakrit W, Povichit N, Suwannalert P (2024) Piceatannol-rich extract from Passiflora edulis Sims seeds attenuates morphological differentiation through the reduction of MITF mRNA expression and F-actin polymerization in UVB-induced hyperpigmented B16F10 cells. J Pharm Pharmacogn Res 12(5): 900–910.

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© 2024 Journal of Pharmacy & Pharmacognosy Research

Immunostimulatory effect of a nature-derived capsule

J. Pharm. Pharmacogn. Res., vol. 12, no. 5, pp. 892-899, Sep-Oct 2024.


Original Article

Potential effects of Linh Loc Son hard capsule – a Vietnamese herbal combination in immunodeficiency induced by cyclophosphamide on mice

[Efectos potenciales de la cápsula dura Linh Loc Son, una combinación de hierbas vietnamitas en la inmunodeficiencia inducida por ciclofosfamida en ratones]

Binh Quoc Pham1, Ngan Kim Thi Nguyen1, Su Quoc Pham1, Cuong Duy Nguyen2, Lam Vu Trinh1, Hang Thu Thi Dinh3, Quang Vinh Trinh3, Van Anh Thi Pham3*

1Vietnam University of  Traditional Medicine, Hanoi, Vietnam.

2Department of Health, Vietnam Ministry of Public Security, Hanoi, Vietnam.

3Hanoi Medical University, Hanoi, Vietnam.



Context: Traditional medicine and herbal extracts have long been recognized for their immunomodulatory effects, enhancing patient immune responses. The use of traditional medicine to target specific pathogens and support the immune system is increasingly studied. Linh Loc Son (LLS) hard capsule, a product derived from nature, consists of the main four natural ingredients: Curculigo orchioides Gaertn., Dioscorea persimilis Prain et Burk., Morinda officinalis F.C.How. and Fallopia multiflora (Thunb.) Haraldson.

Aims: To evaluate the potential effects of LLS hard capsules in complementary treatment of immunodeficiency state in mice.

Methods: An experiment was conducted to assess the impact of LLS hard capsules on an immunosuppressed model of cyclophosphamide-induced Swiss mice of either sex. Two doses of LLS hard capsules (0.69 and 1.38 g/kg body weight) and levamisole (100 mg/kg body weight), serving as a positive control, were administered orally for seven consecutive days; cyclophosphamide (200 mg/kg i.p.) was administered on the fourth day.

Results: Both doses of LLS hard capsule did insignificantly ameliorate the immunosuppressive effects of cyclophosphamide on the delayed-type hypersensitivity response but maintained leukocyte counts, relative organ weight, and cytokines as compared to the levamisole group and showed a significant improvement in micro-histological images.

Conclusions: This study has demonstrated in vivo the immunostimulatory effect of LLS hard capsules, highlighting their potential to boost and regulate the immune response in mice models of immunodeficiency.

Keywords: experimental; herbal medicine; immunologic; immunosuppression

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Contexto: La medicina tradicional y los extractos de hierbas son reconocidos desde hace mucho tiempo por sus efectos inmunomoduladores, que mejoran las respuestas inmunitarias de los pacientes. Se estudia cada vez más el uso de la medicina tradicional para atacar patógenos específicos y apoyar el sistema inmunológico. La cápsula dura Linh Loc Son (LLS), un producto derivado de la naturaleza, consta de los cuatro ingredientes naturales principales: Curculigo orchioides Gaertn., Dioscorea persimilis Prain et Burk., Morinda officinalis F.C.How. y Fallopia multiflora (Thunb.) Haraldson.

Objetivos: Evaluar los efectos potenciales de la cápsula dura de LLS en el tratamiento complementario del estado de inmunodeficiencia en ratones.

Métodos: Se llevó a cabo un experimento para evaluar el impacto de las cápsulas duras de LLS en un modelo inmunosuprimido de ratones suizos de ambos sexos inducidos por ciclofosfamida. Se administraron por vía oral dos dosis de cápsulas duras de LLS (0,69 y 1,38 g/kg de peso corporal) y levamisol (100 mg/kg de peso corporal), que sirvieron como control positivo, por vía oral durante siete días consecutivos; Se administró ciclofosfamida (200 mg/kg i.p.) el cuarto día.

Resultados: Ambas dosis de la cápsula dura de LLS mejoraron de manera insignificante los efectos inmunosupresores de la ciclofosfamida en la respuesta de hipersensibilidad de tipo retardado, pero mantuvieron los recuentos de leucocitos, el peso relativo de los órganos y las citocinas en comparación con el grupo de levamisol y mostraron una mejora significativa en las imágenes microhistológicas.

Conclusiones: Este estudio ha demostrado in vivo el efecto inmunoestimulador de la cápsula dura de LLS, destacando su potencial para estimular y regular la respuesta inmune en un modelo de inmunodeficiencia en ratones.

Palabras Clave: experimental; medicina herbaria; inmunológico; inmunosupresión.

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Citation Format: Binh QP, Ngan NTK, Su QP, Cuong ND, Lam TV, Hang DTT, Quang TV, Van Anh PT (2024) Potential effects of Linh Loc Son hard capsule – a Vietnamese herbal combination in immunodeficiency induced by cyclophosphamide on mice. J Pharm Pharmacogn Res 12(5): 892–899.

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© 2024 Journal of Pharmacy & Pharmacognosy Research

Epidermal growth factor receptor mutant inhibitors as NSCLC drugs

J. Pharm. Pharmacogn. Res., vol. 12, no. 5, pp. 881-891, Sep-Oct 2024.


Original Article

Epidermal growth factor receptor mutant T790M-L858R-V948R inhibitor from Calophyllum inophyllum L. leaf as potential non-small cell lung cancer drugs

[Inhibidor del receptor del factor de crecimiento epidérmico mutante T790M-L858R-V948R de la hoja de Calophyllum inophyllum L. como posible fármaco contra el cáncer de pulmón de células no pequeñas]

Precella Silvia, Jeremi Ongko, Yulanda Antonius*

Faculty of Biotechnology, University of Surabaya, Raya Kalirungkut, Surabaya 60293, Indonesia.



Context: Non-Small Cell Lung Cancer (NSCLC) is the most common lung cancer type, with 80-85% prevalence. Usually, NSCLC is treated by chemotherapy and radiotherapy in collaboration with gefitinib or other anticancer drugs. Those treatments have many adverse effects, such as shortness of breath, bleeding, fever, hair loss, and radiation pneumonitis. Lack of treatment options and numerous mutations greatly contribute to lung cancer’s shocking death toll. Therefore, potential EGFR mutant inhibitors need to be analyzed.

Aims: To identify potential inhibitors of an epidermal growth factor receptor (EGFR) mutant derived from Calophyllum inophyllum L. leaf using an in silico approach.

Methods: In silico analysis and literature study were carried out. Secondary metabolite compounds from C. inophyllum were obtained through the PubChem database, and their biological activity and ADMET were analyzed. Molecular docking with EGFR wild-type (5FED) and mutant (5HG7) was carried out using PyRx. Furthermore, amino acid residues were analyzed using Discovery Studio.

Results: Based on overall screening and molecular docking, a non-toxic compound with a low binding affinity with EGFR mutant protein is 4-[2-(4-nitrophenyl)ethylcarbamoyl]benzenesulfonyl. Moreover, interactions and hydrogen bonds at Ala743, Gly796, Leu718, Phe856, Leu844, and Val726 are known to play a crucial role in ATP binding inhibition toward the tyrosine kinase domain, resulting in EGFR mutant inhibition.

Conclusions: 4-[2-(4-nitrophenyl)ethylcarbamoyl]benzenesulfonyl is one of the potential candidates as an EGFR mutant protein by ATP binding inhibition. However, in vitro and in vivo research needs to be performed to confirm these results.

Keywords: anticancer drug; lung cancer; NSCLC; secondary metabolites; virtual screening.

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Contexto: El cáncer de pulmón no microcítico (CPNM) es el tipo de cáncer de pulmón más frecuente, con una prevalencia del 80-85%. Por lo general, el CPNM se trata mediante quimioterapia y radioterapia en colaboración con gefitinib u otros medicamentos contra el cáncer. Esos tratamientos tienen muchos efectos adversos, como dificultad para respirar, hemorragias, fiebre, caída del cabello y neumonitis por radiación. La falta de opciones de tratamiento y las numerosas mutaciones contribuyen en gran medida a que el cáncer de pulmón se cobre un número de víctimas alarmante. Por lo tanto, es necesario analizar los posibles inhibidores mutantes del EGFR.

Objetivos: Identificar inhibidores potenciales del receptor del factor de crecimiento epidérmico (EGFR) mutante derivado de la hoja de Calophyllum inophyllum L. mediante un enfoque in silico.

Métodos: Se llevó a cabo un análisis in silico y un estudio bibliográfico. Los compuestos de metabolitos secundarios de C. inophyllum se obtuvieron a través de la base de datos PubChem, y se analizó su actividad biológica y ADMET. El acoplamiento molecular con el EGFR de tipo salvaje (5FED) y mutante (5HG7) se llevó a cabo utilizando PyRx. Además, se analizaron los residuos de aminoácidos con Discovery Studio.

Resultados: Basándose en el cribado general y el acoplamiento molecular, un compuesto no tóxico con una baja afinidad de unión con la proteína mutante EGFR es 4-[2-(4-nitrofenil)etilcarbamoil]bencenosulfonil. Además, se sabe que las interacciones y los enlaces de hidrógeno en Ala743, Gly796, Leu718, Phe856, Leu844 y Val726 desempeñan un papel crucial en la inhibición de la unión del ATP hacia el dominio tirosina cinasa, lo que resulta en la inhibición del mutante EGFR.

Conclusiones: El 4-[2-(4-nitrofenil)etilcarbamoil]bencenosulfonil es uno de los candidatos potenciales como proteína mutante del EGFR por inhibición de la unión al ATP. Sin embargo, es necesario realizar investigaciones in vitro e in vivo para confirmar estos resultados.

Palabras Clave: cáncer de pulmón; CPNM; cribado virtual; fármaco anticanceroso; metabolitos secundarios.

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Citation Format: Silvia P, Ongko J, Antonius Y (2024) Epidermal growth factor receptor mutant T790M-L858R-V948R inhibitor from Calophyllum inophyllum L. leaf as potential non-small cell lung cancer drugs. J Pharm Pharmacogn Res 12(5): 881–891.

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© 2024 Journal of Pharmacy & Pharmacognosy Research

Cisplatin-Vernonia amygdalina combination on pancreatic cancer

J. Pharm. Pharmacogn. Res., vol. 12, no. 5, pp. 870-880, Sep-Oct 2024.


Original Article

Combination of cisplatin and ethyl acetate extract of Vernonia amygdalina Delile induces cell cycle arrest and apoptosis on PANC-1 cells via PI3K/mTOR

[Combinación de cisplatino y extracto de acetato de etilo de Vernonia amygdalina Delile induce la detención del ciclo celular y la apoptosis en células PANC-1 vía PI3K/mTOR]

Poppy Anjelisa Zaitun Hasibuan1*, Jane Melita Keliat2, Muhammad Fauzan Lubis3

1Department of Pharmacology, Faculty of Pharmacy, Universitas Sumatera Utara, Medan, 20155, Indonesia.

2Department of Pharmaceutical and Food Analysis, Faculty of Vocational, Universitas Sumatera Utara, Medan, 20155, Indonesia.

3Department of Pharmaceutical Biology, Faculty of Pharmacy, Universitas Sumatera Utara, Medan, 20155, Indonesia.



Context: Vernonia amygdalina Delile (VAD) is known as a potential plant with a wide variety of medicinal properties, including anticancer.

Aims: To evaluate the combination effect of VAD extract with cisplatin (CIS) against PANC-1 cells, focusing on cell cycle arrest and apoptosis activities.

Methods: This study is an experimental study using PANC-1 cells as objects. The phytochemical compounds were analyzed with LC-MS/MS. The cytotoxic activity of extracts and their combinations was determined using the MTT assay method in the PANC-1 cell line. Apoptosis, cell cycle arrest, and PI3K/mTOR profiles were analyzed with flow cytometry. Immunocytochemistry was used to determine Bcl-2, Cyclin D1, and p53 expression.

Results: The phytochemicals found were five compounds with retention times of 8.96, 9.85, 10.52, 12.59, and 10.36. The results of the MTT assay showed that the IC50 values of extract and CIS were 21.83 ± 0.46 µg/mL and 3.02 ± 0.44 µg/mL, respectively. The combination index (CI) value of extract and CIS had a synergistic effect. Combination extract and CIS induced early and late apoptosis, inhibited cell cycle progression on the G1 phase, inhibited Bcl-2 and cyclin D1 expression, induced p53 expression, and inhibited PI3K and mTOR expression.

Conclusions: The combination of extract and CIS showed anticancer activity against PANC-1 cells through induction of apoptosis and cell cycle arrest via inhibition of PI3K and mTOR expressions.

Keywords: apoptosis; cell cycle arrest; cisplatin; herbal medicine; pancreatic cancer.

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Contexto: Vernonia amygdalina Delile (VAD) es conocida como una planta potencial con una amplia variedad de propiedades medicinales, incluyendo anticancerígenas.

Objetivos: Evaluar el efecto combinado del extracto de VAD con cisplatino (CIS) contra las células PANC-1, centrándose en las actividades de detención del ciclo celular y apoptosis.

Métodos: Este estudio es un estudio experimental utilizando células PANC-1 como objetos. El análisis de los compuestos fitoquímicos se llevó a cabo con LC-MS/MS. La actividad citotóxica del extracto y sus combinaciones se determinó mediante el método de ensayo MTT en la línea celular PANC-1. La apoptosis, la detención del ciclo celular y los perfiles PI3K/mTOR se analizaron con citometría de flujo. Se utilizó inmunocitoquímica para determinar la expresión de Bcl-2, ciclina D1 y p53.

Resultados: Los fitoquímicos hallados fueron cinco compuestos con tiempos de retención de 8,96, 9,85, 10,52, 12,59 y 10,36. Los resultados del ensayo MTT mostraron que los valores de IC50 del extracto y del CIS fueron 21,83 ± 0,46 µg/mL y 3,02 ± 0,44 µg/mL, respectivamente. El valor del índice de combinación (IC) del extracto y el CIS tuvo un efecto sinérgico. La combinación de extracto y CIS indujo la apoptosis temprana y tardía, inhibió la progresión del ciclo celular en la fase G1, inhibió la expresión de Bcl-2 y ciclina D1, indujo la expresión de p53 e inhibió la expresión de PI3K y mTOR.

Conclusiones: La combinación de extracto y CIS mostró actividad anticancerígena contra células PANC-1 a través de la inducción de apoptosis y detención del ciclo celular vía inhibición de las expresiones PI3K y mTOR.

Palabras Clave: apoptosis; detención del ciclo celular; cisplatino; fitoterapia; cáncer de páncreas.

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© 2024 Journal of Pharmacy & Pharmacognosy Research

Assessing pharmaceutical patents with the index of internal effort

J. Pharm. Pharmacogn. Res., vol. 12, no. 5, pp. 852-869, Sep-Oct 2024.



Bridging the gap in patent assessment: The Index of Internal Effort framework for pharma innovations

[Bridging the gap in patent assessment: The Index of Internal Effort framework for pharma innovations]

Alisson A. de Oliveira1*, Celso B. dos Santos2, Luiz A. Pilatti3

1Federal Institute of Education of Paraná (IFPR), Curitiba, Paraná, Brazil.

2State University of Ponta Grossa (UEPG), and Federal University of Technology – Paraná (UTFPR), Ponta Grossa, Brazil.

3Postgraduate Program in Production Engineering (PPGEP), Federal University of Technology – Paraná (UTFPR), Ponta Grossa, Brazil.



Context: The process of assessing patents is complex, and there is a gap in the literature on patent assessment at the time of filing.

Aims: To assess patent complexity and the human effort involved in research, we test the effectiveness of the Index of Internal Effort (IIE) framework using pharmaceutical patents developed within the Brazilian public sector as a proof of concept.

Methods: Internal data were collected from innovation projects that included the filing of patents as a project outcome. The Spearman correlation test was applied to determine which internal patent variables could be used as metrics in IIE. Then, IIE was used to measure the complexity of the patents and the individual effort of inventors. Results were then compared with other metrics identified in the literature.

Results: The IIE showed a positive and significant correlation with resources invested at the design stage, as well as commercial and social outcomes of the patents.

Conclusions: The results indicate that the generic IIE framework is a new form of metrification that can be applied to pharmaceutical patents that have not been previously discussed in the literature.

Keywords: data science; Fiocruz; intellectual effort; patent; pharmacology; public service.

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Contexto: El proceso de evaluación de patentes es complejo, y existe un vacío en la literatura sobre la evaluación de patentes en el momento de su presentación.

Objetivos: Evaluar la complejidad de las patentes y el esfuerzo humano implicado en la investigación, la eficacia del marco del Índice de Esfuerzo Interno (IIE), utilizando patentes farmacéuticas desarrolladas dentro del sector público brasileño como prueba de concepto.

Métodos: Se recogieron datos internos de proyectos de innovación que incluían la presentación de patentes como resultado del proyecto. Se aplicó la prueba de correlación de Spearman para determinar qué variables internas de las patentes podían utilizarse como métricas en la IIE. A continuación, se utilizó la IIE para medir la complejidad de las patentes y el esfuerzo individual de los inventores. A continuación, se compararon los resultados con otras métricas identificadas en la bibliografía.

Resultados: La IIE mostró una correlación positiva y significativa con los recursos invertidos en la fase de diseño, así como con los resultados comerciales y sociales de las patentes.

Conclusiones: Los resultados indican que el marco genérico IIE es una nueva forma de metrificación que se puede aplicar a las patentes farmacéuticas que no se han discutido previamente en la literatura.

Palabras Clave: ciencia de datos; esfuerzo intelectual; farmacología; Fiocruz; patente; servicio público.

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