Molecular Docking-Guided Elucidation of Anti-inflammatory Potential of Vitex negundo: Targeting Prostaglandin E Synthase-2 and Cytokine Pathways
Abstract
Background
Chronic inflammation plays a key role in various pathological conditions such as autoimmune diseases and cardiovascular disorders. Conventional anti-inflammatory drugs, though effective, pose risks with prolonged use. Vitex negundo, a medicinal plant widely used in traditional medicine, holds promise as a safer alternative due to its diverse phytochemical profile. However, its detailed cellular and molecular mechanisms remain underexplored.
Objectives
To evaluate the anti-inflammatory and cytoprotective potential of methanolic leaf extract of Vitex negundo using in-vitro assays and in-silico molecular docking, focusing on its modulation of pro-inflammatory cytokines and interactions with key inflammatory targets.
Methods
Molecular docking was performed for key bioactive compounds (e.g., casticin, kaempferol) against prostaglandin E synthase (mPGES-2, PDB: 1Z9H) a pivotal enzyme in prostaglandin biosynthesis using AutoDock Vina, and ADME profiling using SwissADME.
Results
Docking studies revealed Kaempferol and 6,7,4-Trimethoxyflavone as top binders (–7.15 kcal/mol) to mPGES-2, forming multiple stabilizing interactions with active site residues such as Ser166 and Asp239. ADME analysis showed that 7 out of 10 ligands complied with Lipinski’s Rule of Five and had high gastrointestinal absorption, supporting their drug-likeness.
Conclusion
The Vitex negundo exhibits cytoprotective properties and effectively inhibits key pro-inflammatory cytokines. In-silico docking confirms its potential mechanism via direct interaction with mPGES-2. These findings validate its traditional use and support further development as a plant-derived anti-inflammatory therapeutic.
KEYWORDS:
Vitex negundo, anti-inflammatory, cytokines, mPGES-2, molecular docking, natural therapeutics.
