J. Pharm. Pharmacogn. Res., vol. 12, no. 3, pp. 439-452, May-Jun 2024.

DOI: https://doi.org/10.56499/jppres23.1781_12.3.439

Original Article

In silico approaches of gandarusa (Justicia gendarussa Burm. f.) potential for osteoporosis prevention via EGF pathway

[Enfoques in silico del potencial de gandarusa (Justicia gendarussa Burm. f.) para la prevención de la osteoporosis vía EGF]

Sri Dinengsih^1,2*, Nurdiana³, Sri Winarsih⁴, Bambang Raharjo⁵, Agustina Tri Endharti³

¹Doctoral Program of Medical Sciences, Faculty of Medicine, Universitas Brawijaya, Malang 65145, Indonesia.

²Midwifery Program, Faculty of Health Sciences Universitas Nasional, Jakarta, Indonesia.

³Department of Medical, Universitas Brawijaya, Malang 65145, Indonesia.

⁴Department of Pharmacology, Universitas Brawijaya, Malang 65145, Indonesia.

⁵Department of Obstetric Gynecology, Public Hospital of Saiful Anwar, Malang, Indonesia.

*E-mail: sridinengsih@civitas.unas.ac.id

Abstract

Context: On a cellular level, osteoporosis is a metabolic bone disease caused by osteoclastic bone resorption that is not offset by osteoblastic bone synthesis. This increases the risk of fractures by making bones weak and brittle. The selective inactivation of the epidermal growth factor receptor (EGFR) in osteoblast lineage cells demonstrated that EGFR promotes bone formation by increasing the number of mesenchymal progenitors. Active compounds of gandarusa (Justicia gendarussa Burm. f.) are potentially playing crucial roles in EGFR activation.

Aims: To evaluate the potential of J. gendarussa for osteoporosis prevention via EGF pathway in silico.

Methods: A GC-MS approach was used to screen the active compounds from 70 and 95% methanol extraction, which was continued with molecular docking analysis by PyRx v0.8. The visualization and amino acid interactions were also revealed using Discovery Studio software R17. ADME analysis was performed using the SwissADME webserver to consider whether the best compound could be classified as a drug following Lipinsky rule’s of five.

Results: The top five compounds with high binding affinity were selected from a total of 33 active compounds detected. One compound, namely eslicarbazepine, has a -6.7 kcal/mol affinity score and passes the threshold for drugs bioavailability, supported by the data of MW compounds 254.28 kDa, low rotatable bonds 1 bond, hydrogen bond acceptors and donors (2), high GI absorption, and ability to permeant to blood-brain barrier system.

Conclusions: This finding added new insight into J. gendarussa extract potential as anti-osteoporosis in humans. Nevertheless, in vitro and in vivo experiments are necessary to confirm the potential.

Keywords: activation; ADME; bone formation; leaf extract; molecular docking.

Resumen

Contexto: A nivel celular, la osteoporosis es una enfermedad ósea metabólica causada por una resorción ósea osteoclástica que no se ve compensada por la síntesis ósea osteoblástica. Esto aumenta el riesgo de fracturas al hacer que los huesos se vuelvan débiles y quebradizos. La inactivación selectiva del receptor del factor de crecimiento epidérmico (EGFR) en células del linaje de los osteoblastos demostró que el EGFR favorece la formación ósea al aumentar el número de progenitores mesenquimales. Los compuestos activos de la gandarusa (Justicia gendarussa Burm. f.) desempeñan potencialmente papeles cruciales en la activación del EGFR.

Objetivos: Evaluar el potencial de J. gendarussa para la prevención de la osteoporosis a través de la vía EGF in silico.

Métodos: Se utilizó un enfoque GC-MS para cribado de los compuestos activos de 70 y 95% de extracción de metanol, que se continuó con el análisis de acoplamiento molecular por PyRx v0.8. La visualización y las interacciones de aminoácidos también se revelaron mediante el software Discovery Studio R17. El análisis ADME se realizó utilizando el servidor web SwissADME para considerar si el mejor compuesto podía clasificarse como fármaco siguiendo la regla de los cinco de Lipinsky.

Resultados: Se seleccionaron los cinco compuestos con mayor afinidad de unión de un total de 33 compuestos activos detectados. Un compuesto, a saber, la eslicarbazepina, tiene una puntuación de afinidad de -6,7 kcal/mol y supera el umbral de biodisponibilidad de los fármacos, apoyado por los datos de compuestos con un MW de 254,28 kDa, bajo enlace rotatorio 1, aceptores y donantes de enlaces de hidrógeno (2), alta absorción GI y capacidad de permeabilidad al sistema de barrera hematoencefálica.

Conclusiones: Este hallazgo añade nuevos conocimientos sobre el potencial del extracto de J. gendarussa como antiosteoporosis en humanos. No obstante, son necesarios experimentos in vitro e in vivo para confirmar dicho potencial.

Palabras Clave: acoplamiento molecular; activación; ADME; extracto de hoja; formación ósea.

 

https://jppres.com/jppres/pdf/vol12/jppres23.1781_12.3.439.pdf

 

 

Citation Format: Dinengsih S, Nurdiana, Winarsih S, Raharjo B, Endharti AT (2024) In silico approaches of gandarusa (Justicia gendarussa Burm. f.) potential for osteoporosis prevention via EGF pathway. J Pharm Pharmacogn Res 12(3): 439–452. https://doi.org/10.56499/jppres23.1781_12.3.439

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