• Madhuca longifolia flowers contain compounds with anti-obesity potential • Multi-target analysis identified 17 key genes linked to obesity pathways • ADIPOR1, INSR and LEPR emerged as central metabolic regulatory targets • Sterol and polyphenol compounds showed strongest multi-receptor binding • Triple enzyme inhibition and hormonal pathway modulation suggest synergistic effects Obesity keeps rising around the world, and many synthetic drugs used to treat it have severe side effects. Because of this, plant-based alternatives has been growing. Madhuca longifolia flowers have traditionally been used to suppress appetite, making them a possible source of natural compounds to explore for obesity management. Our earlier work showed that some Mahua compounds may inhibit lipase In this study, the scope was widened to examine whether these compounds can also affect α-amylase, β-glucosidase, and key receptors involved in metabolism. Out of 97 reported compounds, eight showed good drug-likeness and were selected for further study. Target prediction and gene overlap analysis identified 17 genes connected to obesity. A protein–protein interaction network and functional enrichment analyses were conducted to explore biological relevance. Molecular docking was performed to evaluate binding interactions with selected metabolic receptors The protein–protein interaction network indicated insulin, leptin, and adiponectin-related signalling as central regulatory routes. Enrichment analysis confirmed involvement of these genes in glucose metabolism, appetite control, and energy balance. Molecular docking showed that sterol and polyphenol based compounds had the strongest binding across the metabolic receptors. For adiponectin receptor 1, beta-sitosterol scored -12.5 kcal/mol and beta-carotene -12.2 kcal/mol; for the insulin receptor, beta-carotene scored -7.4 kcal/mol, folic acid -7.2 kcal/mol, and riboflavin -6.8 kcal/mol; for the leptin receptor, beta-carotene reached -8.0 kcal/mol and beta-sitosterol -7.9 kcal/mol. Several residues were repeatedly observed as key interaction points, suggesting consistent binding behaviour The findings suggest that compounds from Madhuca longifolia flowers may influence obesity by acting on both digestive enzymes and hormone-related pathways. These results support further experimental validation for developing safer, plant-based strategies for obesity management.
Gayakvad et al. (Sun,) studied this question.