Unveiling antidiabetic mechanisms of Raphanus sativus L. leaves: a multidimensional approach combining in vitro, in vivo, and in silico studies
摘要
Raphanus sativus L., a member of the Brassicaceae family, has been traditionally used for various therapeutic purposes, including antidiabetic activity. Though the antidiabetic effects of Raphanus sativus leaf have been identified, the mechanisms underlying its antihyperglycemic activity have not been thoroughly investigated. This study focuses on elucidating those mechanisms using in vitro, in silico, and in vivo approaches. In vitro assays using HepG2 cells assessed cytotoxicity (MTT assay), glucose uptake, phosphorylated PKC levels, and DPP-IV enzyme inhibition. The extract exhibited an IC₅₀ of 71.15 µg/mL in the anti-inflammatory hemolysis assay and maintained 78.26% cell viability at 100 µg/mL, which was selected for further assays. In vivo studies employed a streptozotocin-nicotinamide-induced type 2 diabetic rat model, showing significant reductions in blood glucose, lipid peroxidation, and improvements in HDL, antioxidant enzymes (GSH, SOD, CAT), and histopathological restoration. Apoptotic markers indicated protection against diabetes-induced cellular damage. In silico molecular docking identified six top-binding compounds with strong affinities for DPP-IV, supporting the observed bioactivity. ADMET profiling confirmed favorable pharmacokinetic and toxicity parameters compared to sitagliptin. These findings suggest that Raphanus sativus leaf extract exerts antidiabetic effects through glucose regulation, oxidative stress reduction, and apoptosis inhibition, validating its therapeutic potential against type 2 diabetes mellitus.