Network Pharmacology‒Guided in Silico Screening and Molecular Dynamics Investigation of Madecassoside for Leprosy

Leprosy is a chronic infection primarily affecting populations in Asia and other developing regions. Although current treatments are often effective, they lead to side effects and drug resistance. This study evaluates the therapeutic potential of madecassoside from Centella asiatica as multi‐target agent against leprosy. Network pharmacology was performed to identify the potential targets of madecassoside for leprosy treatment. Molecular docking was conducted to determine the binding affinities of madecassoside against selected proteins. MD simulations and MM/GBSA were performed to determine complex stability and conformational behavior. The study identified 19 overlapping genes through network pharmacology, including PTGS2, IL2, NFKB1 , and TLR4 as key targets. GO and KEGG analyses revealed the potential pathways associated with immune and inflammatory signaling. Madecassoside was found to have a strong binding affinity to the selected targets, PTGS2 (−11.36 kcal/mol), IL2 (−8.22 kcal/mol), NFkB1 (−8.08 kcal/mol), and TLR4 (−7.39 kcal/mol), compared to standard dapsone. MD simulations of PTGS2 and IL2 complexes remained stable throughout the 100 ns, with only minor fluctuations. Furthermore, MM/GBSA further supported the results of docking and dynamics. The present work demonstrated that madecassoside is a promising alternative for leprosy. Further preclinical studies are needed to confirm its efficacy and advance drug development.