Goli A.S.Sato V.H.Sato H.Chewchinda S.Leanpolchareanchai J.Nontakham J.Yahuafai J.Thilavech T.Meesawatsom P.Maitree M.Mahidol University2023-05-192023-05-192023-01-01Pharmaceutical Biology Vol.61 No.1 (2023) , 189-20013880209https://repository.li.mahidol.ac.th/handle/20.500.14594/82610Context: Lysiphyllum strychnifolium (Craib) A. Schmitz (LS) (Fabaceae) has traditionally been used to treat diabetes mellitus. Objective: This study demonstrates the antidiabetic and antioxidant effects of aqueous extract of LS leaves in vivo and in vitro. Materials and methods: The effects of aqueous LS leaf extract on glucose uptake, sodium-dependent glucose cotransporter 1 (SGLT1) and glucose transporter 2 (GLUT2) mRNA expression in Caco-2 cells, α-glucosidase, and lipid peroxidation were evaluated in vitro. The antidiabetic effects were evaluated using an oral glucose tolerance test (OGTT) and a 28-day consecutive administration to streptozotocin (STZ)-nicotinamide (NA)-induced type 2 diabetic mice. Results: The extract significantly inhibited glucose uptake (IC50: 236.2 ± 36.05 µg/mL) and downregulated SGLT1 and GLUT2 mRNA expression by approximately 90% in Caco-2 cells. Furthermore, it non-competitively inhibited α-glucosidase in a concentration-dependent manner with the IC50 and Ki of 6.52 ± 0.42 and 1.32 µg/mL, respectively. The extract at 1000 mg/kg significantly reduced fasting blood glucose levels in both the OGTT and 28-day consecutive administration models as compared with untreated STZ-NA-induced diabetic mice (p < 0.05). Significant improvements of serum insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and GLUT4 levels were observed. Furthermore, the extract markedly decreased oxidative stress markers by 37–53% reduction of superoxide dismutase 1 (SOD1) in muscle and malondialdehyde (MDA) in muscle and pancreas, which correlated with the reduction of MDA production in vitro (IC50: 24.80 ± 7.24 µg/mL). Conclusion: The LS extract has potent antihyperglycemic activity to be used as alternative medicine to treat diabetes mellitus.MedicineArticleSCOPUS10.1080/13880209.2022.21607712-s2.0-851459559881744511636625086