Possible Mechanism of Antidepressant Action from Phyllanthus emblica Fruit using Pharmacological Network Analysis and Molecular Docking
Novi Ayuwardani1,6, Zullies Ikawati2*, Nanang Fakhrudin3,5 and Zaenal Muttaqien Sofro4
1California Northstate University College of Medicine, Elk Grove, CA, USA
2Departement of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara, Yogyakarta, Indonesia
3Departement of Pharmaceutical Biology, Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara, Yogyakarta, Indonesia
4Departement of Physiology, Faculty of Medicine, Nursing, and Public Health, Univeristas Gadjah Mada, Sekip Utara, Yogyakarta, Indonesia
5Medicinal Plants and Natural Products Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara, Yogyakarta, Indonesia
6Departement of Pharmacy, STIKES Bhakti Husada Mulia, Madiun, Indonesia
*Corresponding Author: Zullies Ikawati, Departement of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara, Yogyakarta, Indonesia.
Received:
November 04, 2024; Published: November 29, 2024
Abstract
The fruit of Phyllanthus emblica, also known as amla fruit, has been reported to have potential an antidepressant effects due to its high content of phenolic compounds. However, the mechanism underlying the antidepressant effect remains unclear. Therefore, this study aims to explore the mechanism of action of P. emblica fruit extract for antidepressant activity using network pharmacology and molecular docking. The compound components of the extract were obtained from untargeted metabolomic LC-HRMS, P. emblica-related targets, and depression therapeutic targets from an extensive database. Protein-protein interaction networks were constructed to screen the core targets using the STRING database and Cytoscape software. Metascape database was used for GO enrichment and KEGG analysis. Then, the top ten pathways were selected to construct a network analysis of compound components, disease proteins, and signaling pathways. In addition, molecular docking was used to explore and verify the interaction of compound components with core targets. Our study identified 9 compound components and 94 potential targets from P. emblica as antidepressants. The PPI network identified MAOA, COMT, SLC6A3, MAOB, DRD2, SLC6A4, and SNCA as possible targets, while GO enrichment and KEGG analysis showed that the relevant biological processes involved in the treatment of depression by P. emblica included synaptic signaling and behavior, and the molecular function included neurotransmitter receptor activity. The results of the KEGG pathway analysis identified serotonergic synapse and dopaminergic synapse signaling pathways associated with core targets. Gallic acid and ellagic acid components were selected to view the binding interaction with core targets related to molecular docking, which resulted in ellagic acid with strong binding affinity. Our study provides insight into the potential of P. emblica fruit for treating depression as a basis for further validation and exploration of experimental research.
Keywords: Phyllanthus Emblica; Depression; Network Pharmacology; Molecular Docking; Neurotransmitter Receptor Activity
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