Modification of novel gymnemic acid enrich extract to Ag-nanoparticles and lipid soluble derivative for the amelioration of insulin impairment in L6 myoblasts

Gymnema sylvestre (Retz.) R.Br. ex. Sm. is a well-known hypoglycemic plant that contains gymnemic acids (GAs). GAs are biologically active molecules but their limited lipid/water solubility and high molecular weight are the significant factors for their delayed biological action. Hence, a novel greener process has been developed for the preparation of GAs enriched extract (Gym-CA) and further physicochemical modifications are performed on Gym-CA in order to increase its bioavailability. pH of the crude hydro-ethanolic extract (Gym-Crude) was maintained at 3.0 using citric acid solution (0.5 M) to obtain Gym-CA, and standardizations were performed with Rp-HPLC. Gym-CA was acetylated using acetic anhydride and DMAP for 30 min to obtain lipid soluble extract (Gym-Ace), and treated with 10 mM AgNO3 solution at 90 degrees C for 2 h to produce Gym-Ag-NPs. Physical char-acterization of Gym-Ag-NPs was performed via UV-Vis, FT-IR, DLS, TGA, SEM, TEM, XRD and XPS techniques. All the preparations along with standard GAs (deacylgymnemic acid, gymnemagenin and GA-IV) were analyzed In-vitro on L6 skeletal myoblasts and In-silico on TNF-alpha and PPAR-gamma for comparative Improved Glucose Uptake potential (IGUP) studies. GA-IV was found to have highest affinity towards TNF-alpha (-9.1 kcal/mol) and DAG have highest affinity (-7.4 kcal/mol) towards PPAR-gamma. Interestingly, Gym-Ag-NPs displayed significant IGUP (99.88%). In conclusion, particle size is inversely correlated to the bioavailability and biological actions of GAs. For future prospects, formulations containing nano-sized GAs as principal active ingredients could be a suitable candidate for the treatment of insulin impaired patients after In-vivo validations.