Exploration of Antidiabetic and Anti-Apoptotic Activity of Cissus quadrangularis Stem Through Mechanistic Pathway: An in vitro, in silico and in vivo Approach.

In the twenty-first century, across the world, there are few ethnomedical solutions for treating type 2 diabetes mellitus (T2DM), a common metabolic disease and its associated disorders. The present study assessed the hypoglycaemic effects of an extract from the stem of Cissus quadrangularis in a rat model with the addition of in vitro and in silico investigations specifically α-amylase, α-glucosidase inhibitory tests and molecular docking, molecular dynamics (MD) simulation study. Streptozotocin and nicotinamide were used to generate type 2 diabetes in rats. Thereafter, Cissus quadrangularis (CQ) stem extract was given orally for 28 days at doses of 200 and 400 mg/kg body weight. The extract improved biochemical indicators, lowered lipid peroxidation, raised HDL levels, and decreased blood glucose in a dose-dependent manner. Tissue healing in treated groups was confirmed by histopathological examination. The α-amylase and α-glucosidase inhibition assays had respective IC₅₀ values of 50.18 ± 2.67 µg/ml and 50.93 ± 1.79 µg/ml which are pretty much comparable with the standard, acarbose. By measuring apoptotic proteins such as BAX, BCL2, caspase 3, and caspase 9, the results show that the extract has a considerable effect on preventing cell death. The introduction of CQ stem extract to the experimental animals elevates the glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT), suppressing the amount of thiobarbituric acid relative substance (TBARS) in liver tissue. These findings from in vitro, in vivo, and in silico research suggest the potential of CQ stem extract as a preventive measure against apoptosis and an alternative therapeutic strategy for type 2 diabetes by activating the adenosine 5'-monophosphate/phosphatidylinositol 3-kinase/protein kinase B (AMPK/PI3K/AKT) signalling pathway.