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Network pharmacology, molecular docking and molecular dynamics analysis reveal multi-target mechanisms of Imperata
Akshay Shamnewadi1, Shamanand P Mallapur2, Vishal S Patil2
1Department of Pharmaceutics, KLE College of Pharmacy, Hubballi, KLE Academy of Higher Education and Research, Deemed-to-be-University, Nehru Nagar, 590010, Belagavi, India.
Objectives:
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder marked by persistent synovial inflammation and joint destruction. Limitations of current therapies due to adverse effects and incomplete efficacy necessitate multi-target treatment strategies. Imperata cylindrica (L.) Raeusch., rhizome known as Bai Mao Gen in Traditional Chinese Medicine and Darbha in Ayurveda, has been traditionally used for inflammatory conditions; however, its molecular mechanisms in RA remain unclear.
Methods:
An integrative in silico approach combining network pharmacology, molecular docking, and molecular dynamics simulations was employed. Phytoconstituents of Imperata cylindrica were obtained from the IMPPAT database and screened for drug-likeness and ADME properties using SwissADME. Potential targets were predicted via SwissTargetPrediction and intersected with RA-related genes from GeneCards, followed by GO and KEGG pathway enrichment using STRING and network construction. Key RA targets (IKBKB, JAK1, and PTGS2) were validated by molecular docking, and the stability of selected complexes was evaluated through 100ns MD simulations.
Results:
Flavonoids and sesquiterpenes, including 4',5,6,7-tetramethoxyflavone, eupatorin, cylindol A, and cylindrene, exhibited favorable drug-likeness and pharmacokinetic profiles. Network analysis identified 53 common targets, highlighting IKBKB, JAK1, and PTGS2 as central inflammatory mediators. Docking studies demonstrated strong binding affinities of selected phytoconstituents towards these targets, comparable to standard inhibitors. MD simulations confirmed the dynamic stability of PTGS2-eupatorin and PTGS2-4',5,6,7-tetramethoxyflavone complexes.
Conclusion:
This study provides mechanistic insights into the anti-rheumatoid potential of Imperata cylindrica, identifying key phytoconstituents such as eupatorin and 4',5,6,7-tetramethoxyflavone as multi-target modulators of IKBKB, JAK1, and PTGS2 in NF-κB, JAK-STAT, and COX-2 pathways, supporting its therapeutic potential and warranting further experimental validation.
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