DIRECT ACTIVATOR OF AMPK FROM SHILAJIT: A BIOINFORMATICS-BASED STUDY

Metabolic syndrome is continuously on the rise, due to a changed lifestyle and long ageing. The abnormal function of mTOR/AMPK, a cellular energy switch, is the main cause behind this pathogenesis, which is now defined as “metabolic syndrome”. Here, we have screened the metabolites of shilajit, obtained from the HRAMS analysis, to select the direct activators of AMPK, by using computational exploration, through molecular docking and ADMET prediction. The shilajit has been in clinical use in Ayurvedic medicine, for centuries, to enhance the overall vitality, immunocompetence and aphrodisiac potential, but scientific data are lacking to support its therapeutic claims. The shilajit, of Upakarma Ayurveda was purchased from the market and analyzed through HRAMS, which reported the presence of 5467 metabolites. Their CID numbers were obtained from the PubChem portaland docked against the AMPK (AMPK active site PDB ID-4CFF), by using LibDock and Discovery Studio to do a structure-based screening, ADME (absorption, distribution, metabolism, excretion) and toxicity prediction. Among them, Reproterol (CID-25654) and Ambruticin (CID-6918547) showed the best binding energy, in comparison to standard drug “A-769662 (CID: 54708532)”. These metabolites can be used as a lead molecule to develop novel activators of AMPK. This study also supports the therapeutic claims of the use of Shilajit, for the management of metabolic syndrome. Helps in understanding its mechanism of action for other claims, involving AMPK-linked pathways.