Metabolomic profiling, in-vitro and in-silico analysis of Ayurvedic formulation Madhumehantak Churna, identifies Ptelatoside A as a potent anti-diabetic biomolecule.

Diabetes is a 21st-century epidemic affecting 10.1 crores Indians as of 2023. Ayurveda, a traditional indigenous medical practice, can be leveraged to manage diabetes, as the allopathic antihyperglycemic drugs are reported to cause severe repercussions. This study employs a combinatorial integrated approach to explore the scientific anti-diabetic prophylaxis of Madhumehantak Churna, an Ayurvedic formulation. Hydroalcoholic extract of Madhumehantak Churna (MCH) exhibited robust in-vitro enzyme inhibition and antioxidant assays. Out of 36 major phytocompounds identified by LC-MS profiling in MCH, ProTox 3.0 identified 29 phytocompounds with no significant toxicity, screened based on their toxicity (LD₅₀). These were subjected to integrated Network pharmacology and bioinformatics, involving in-silico molecular docking, ADMET, homology modelling and simulation studies. In-silico molecular docking studies of 29 compounds with 28 proteins, including GLUT12, Myeloperoxidase, Phosphodiesterase 4D, Cathepsin B, Cathepsin S identified from literature studies and network pharmacology, devised by STRING and CYTOSCAPE, highlighted that Ptelatoside A showed the strongest binding affinities. In-silico pharmacokinetics and ADMET analysis predicted Ptelatoside A, a glucoside, to possess the requisite drug likeness parameters. GROMACS-assisted Molecular dynamics simulation (MDS), PCA and KEGG pathway identified insulin resistance and insulin signalling pathways as the probable underlying molecular actions of Ptelatoside A against diabetes mellitus. The combinatorial study involving in-vitro anti-diabetic assessments, network pharmacology, molecular docking, in-silico pharmacokinetics, PCA analysis and simulation studies, underscores that the glycoside Ptelatoside A from the Ayurvedic formulation, Madhumehantak Churna, can be a future solution for anti-hyperglycemic drug development.

Graphical abstract:

Supplementary information: The online version contains supplementary material available at 10.1007/s40203-025-00430-5.