Evaluation of Acute toxicity, In-vitro, In-vivo Antidiabetic Potential of the Flavonoid Fraction of the plant Chenopodium album L

Background: The Chenopodium album L. commonly recognized as Bathua, is widely distributed globally and contains various phytoconstituents that help treat several diseases. However, until now, aerial parts' antidiabetic potential and the plant's acute toxicity at fraction level have never been established. Objectives: To investigate the acute toxicity, the in-vitro, in-vivo antidiabetic potential of the plant at fraction level. Materials and Methods: The aerial parts of the plant were fractionated into different fractions, i.e., flavonoid fraction (CAFF), tannin fraction (CATF), alkaloid fraction (CAAF), saponin fraction (CASF), and were analyzed for in-vitro alpha-amylase inhibition assay. The CAFF, CATF, and CAAF were selected based on in-vitro alpha-amylase inhibition assay results and were further screened for its acute toxicity and in vivo antidiabetic activity using a high-fat diet and streptozotocin-induced diabetes model. The CAFF was characterized by LC-MS, and a molecular docking study was carried out. Results: The in-vitro alpha-amylase inhibition assay revealed that CAFF was found to be more potent than standard Acarbose having IC₅₀ values 122.18 ± 1.15 and 812.83± 1.07 μg/ml, respectively. The CAFF fraction was found to possess potent antidiabetic activity in a dose-dependent manner in both in vitro and in vivo diabetic models and did not produce any sign of severe toxicity. Furthermore, the bioactive CAFF fraction was characterized by LC-MS, showed the presence of quercetin 3-O-(2’’,6’’-di-O-rhamnosyl) glucoside (QRG) or quercetin 3-O-(2’’,6’’-di-Orhamnosyl) galactoside (QRGa) and quercetin 3-O-rutinoside (rutin) (QR). It is predicted from the molecular docking study that the CAFF fraction primarily acts as an alphaamylase inhibitor. Conclusion: The CAFF fraction was found to poses dose-dependent potent antidiabetic activity and did not produce any sign of severe toxicity and primarily act as an alpha-amylase inhibitor.