Withania somnifera modulates glucose metabolism by inhibiting SGLT2, α- glucosidase and α-amylase: An in silico and in vitro study

Diabetes is a growing metabolic disease worldwide, and effective approaches to treatment are needed. The study sought to comprehend the mechanistic role of Ashwagandha (Withania somnifera L.) root extract in regulating hyperglycaemia. Withania somnifera (W. somnifera) is known for its medicinal properties. In vitro and in silico approaches were employed to explore the antidiabetic properties of W. somnifera metabolites identified by GC-MS analysis.This work investigated the antidiabetic activities of W. somnifera metabolites using GC-MS analysis in vitro and In silico. We performed a qualitative phytochemical screening as well as a free radical scavenging studies using the DPPH+ and ABTS+ assays. Additionally, α-amylase and α-glucosidase inhibition experiments were performed. Molecular docking studies were done using compounds found from W. somnifera root extract against target proteins sodium-glucose transport protein 2 (SGLT2), α-glucosidase, and α-amylase. A qualitative examination revealed that W. somnifera contained phenols, steroids, and terpenoids. The DPPH+ and ABTS+ free radical scavenging experiments demonstrated high antioxidant activity, with IC50 values of 37.8 and 34.4 μg/mL, respectively. W. Somnifera inhibited α-amylase and α-glucosidase enzymes at doses of 3.25–50 µg/mL. Docking experiments demonstrated high binding affinities of -9.6 to -3.5 kcal/mol, -11.8 to -5.5 kcal/mol, and -9.3 to -4.5 kcal/mol, respectively. In conclusion, our studies revealed that phytochemicals present in W. somnifera inhibited SGLT-2, a glucose transporter, as well as α-amylase and α-glucosidase enzymes. Furthermore, our docking analysis supported in vitro findings. These data demonstrate that W. somnifera can regulate blood sugar levels and can be used as an alternative traditional medicine for diabetes therapy.