Exploring phytoconstituents for Parkinson’s disease: Insights from network pharmacology, molecular modeling and in vivo investigations

Authors

Shiva Priya, JSS College of Pharmacy, OotyFollow
Divakar Selvaraj, Prime College of PharmacyFollow
Rashi Jain, JSS College of Pharmacy, OotyFollow
Kavyashree G. S., JSS College of Pharmacy, OotyFollow
Soumya V., Faculty of pharmacy, Sri Ramachandra Institute of Higher Education and ResearchFollow
Venkatesh Gunasekaran, PSG College of Pharmacy, CoimbatoreFollow
Ramu G., Al Shifa College of Pharmacy, PerintalmannaFollow
Saravanan Jayaram, JSS College of Pharmacy, OotyFollow

Abstract

Background: The network pharmacology approach is used to identify novel therapeutic agents that target multiple disease targets through analysis of complex disease networks by integrating systems biology and computational approaches. Objectives: The present study aims to identify the principal targets implicated in the pathogenesis of Parkinson’s disease (PD) and major phytoconstituents that could potentially modulate the major targets to achieve therapeutic benefits in PD through a network pharmacology-based approach. Materials and Methods: The DisGeNET database was used to select the major targets involved in the pathogenesis of PD. The most important targets among the selected proteins were identified through analysis of topological parameters, such as degree, betweenness centrality, and closeness centrality using Cytoscape software. The phytoconstituents present in the selected botanicals were identified from databases and were subjected to the prediction of pharmacokinetic parameters. The binding affinity, free energy, and binding stability of the selected phytochemicals with the target proteins were evaluated using molecular docking, MM-GBSA, and molecular dynamics (MD), respectively, using Schrodinger software. The effect of berberine on catalepsy, motor coordination, locomotion, and memory was evaluated using rotenone-induced PD in rats.
Results: Based on topological parameters and pharmacokinetic profile, 4 proteins (A2A, CNR1, REN, and STAT3) and 6 phytoconstituents (berberine, bisacumol, capsaicin, ferulic acid, cinnamic acid, and geranyl acetate) were selected, respectively, for further studies. Among the chosen ligands, berberine exhibited maximum binding affinity with A2A (−9.90 kcal/mol), REN (−7.89 kcal/mol), STAT3 (−3.93 kcal/mol), and second highest with CNR1 (−9.07 kcal/mol). Berberine also showed better free energy scores in MM-GBSA with three targets, A2A (−86.44 kcal/mol), REN (−108.93 kcal/mol), and CNR1 (75.18 kcal/mol). The root mean square deviation of berberine with all four targets in MD indicated good ligand-target stability. A significant improvement in the catalepsy test, motor coordination, locomotion, and memory in animals treated with 25 and 50 mg/kg of berberine compared with the control group.
Conclusion: The current network pharmacology-based study reveals that berberine could act as a beneficial agent in PD through the alteration of multiple receptors.

DOI

10.56808/3027-7922.3050

Recommended Citation

Priya, Shiva; Selvaraj, Divakar; Jain, Rashi; G. S., Kavyashree; V., Soumya; Gunasekaran, Venkatesh; G., Ramu; and Jayaram, Saravanan (2025) "Exploring phytoconstituents for Parkinson’s disease: Insights from network pharmacology, molecular modeling and in vivo investigations," The Thai Journal of Pharmaceutical Sciences: Vol. 49: Iss. 4, Article 4.
DOI: https://doi.org/10.56808/3027-7922.3050
Available at: https://digital.car.chula.ac.th/tjps/vol49/iss4/4