In-silico reverse docking and in-vitro studies identified curcumin, 18α-glycyrrhetinic acid, rosmarinic acid, and quercetin as inhibitors of α-glucosidase and pancreatic α-amylase and lipid accumulation in HepG2 cells, important type 2 diabetes targets

Several therapeutic targets have been identified for the management of type 2 diabetes (T2D), including the inhibition of α-amylase and α-glucosidase. The present study determined the ability of curcumin, 18α-glycyrrhetinic acid, quercetin and rosmarinic acid to inhibit α-amylase, α-glucosidase, and hepatic lipid accumulation. In-silico enzyme inhibitory abilities of the compounds were assessed using docking analysis with Maestro and AutoDock vina. In-vitro biochemical assays were used to confirm docking studies; 3.5-dinitrosalicylic acid (DNSA) and p-nitrophenyl-α-D-glucopyranoside (pNPG) assays for α-amylase and α-glucosidase inhibition, respectively. The ability to reduce lipid accumulation in HepG2 cells for NAFLD was evaluated. The relationships between in-silico and in-vitro inhibition results correlated well; a more negative docking score correlated with a lower inhibition constant (K i ). For α-amylase, the K i values of the compounds were significantly higher (p < 0.05) than acarbose. For α-glucosidase, the K i values of curcumin, 18α-glycyrrhetinic acid (18α-GA), and quercetin were significantly lower (p < 0.05) than acarbose. The IC 50 was determined for these compounds in HepG2 cells. At the concentrations used to evaluate OA-induced lipid accumulation, the compounds were not cytotoxic. All compounds and metformin significantly reduced (p < 0.05) lipid accumulation in HepG2 cells. Herbs/spices are rich sources of these compounds, providing a cost-effective, easily cultivated, and readily available source of compounds that can alleviate T2D symptoms. Curcumin is found in turmeric and rosmarinic acid in rosemary, where a dose of 1.3 g of turmeric or 1.6 g of rosemary is equivalent to 50 mg acarbose per meal.