Network Pharmacology Reveals Key Targets and Pathways of Madhuca longifolia for Potential Alzheimer's Disease Treatment

Madhuca longifolia, commonly known as the mahua tree, has been traditionally used in medicine due to its anti-inflammatory, anti-diabetic, and antimicrobial properties. Its active compounds help in managing diabetes, alleviating cognitive impairment associated with Alzheimer's disease. Nonetheless, the exact neuroprotective mechanism of Madhuca longifolia against Alzheimer's disease remains unclear. This study looked into possible methods by which Madhuca longifolia protects against Alzheimer's disease using network pharmacology, molecular docking and molecular dynamic simulations studies. By applying pre-screening of active constituents, target prediction, Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis, our study found that Madhuca longifolia is related to eight active ingredients (Ascorbic acid, Riboflavin, Pantothenic acid, (4 R)-2beta,3beta,23-trihydroxy-oleana-5,12-dien-28-oic acid, Quercetin, Nicotinic acid, Bassiaic acid Thiamine) and 272 common gene targets, with significant involvement in pathways such as PI3K-Akt signaling and neuroactive ligand-receptor interaction. Network analysis demonstrated how Madhuca longifolia can prevent AD by modifying important signalling networks, which may be one of the molecular mechanisms driving the plant's effectiveness against the disease. Molecular docking studies revealed that there were robust binding abilities of Quercetin, Riboflavin and Pantothenic acid to key target proteins AKT1, JUN, and STAT3. Later, molecular dynamic simulations was done to examine the successful activity of the active compounds against potential targets, and it was found that AKT1 and AKT1-Quercetin complex became stable at 260 ps. It may be seen through the study that quercetin may act as a good inhibitor for treatment. This thorough investigation provides a strong basis for future research and development efforts by advancing our understanding of Madhuca longifolia medicinal potential in Alzheimer's disease.