In Vivo and In Vitro Antidiabetic Efficacy of Aqueous and Methanolic Extracts of Orthosiphon Stamineus Benth.

is a popular folk herb used to treat diabetes and some other disorders. Previous studies have shown that extracts were able to balance blood glucose levels in diabetic rat animal models. However, the antidiabetic mechanism of is not fully known. This study was carried out to test the chemical composition, cytotoxicity, and antidiabetic activity of (aerial) methanol and water extracts. GC/MS phytochemical analysis of methanol and water extracts revealed 52 and 41 compounds, respectively. Ten active compounds are strong antidiabetic candidates. Oral treatment of diabetic mice with extracts for 3 weeks resulted significant reductions in blood glucose levels from 359 ± 7 mg/dL in diabetic non-treated mice to 164 ± 2 mg/dL and 174 ± 3 mg/dL in water- and methanol-based-extract-treated mice, respectively. The efficacy of extracts in augmenting glucose transporter-4 (GLUT4) translocation to the plasma membrane (PM) was tested in a rat muscle cell line stably expressing myc-tagged GLUT4 (L6-GLUT4myc) using enzyme-linked immunosorbent assay. The methanol extract was more efficient in enhancing GLUT4 translocation to the PM. It increased GLUT4 translocation at 250 µg/mL to 279 ± 15% and 351 ± 20% in the absence and presence of insulin, respectively. The same concentration of water extract enhanced GLUT4 translocation to 142 ± 2.5% and 165 ± 5% in the absence and presence of insulin, respectively. The methanol and water extracts were safe up to 250 µg/mL as measured with a Methylthiazol Tetrazolium (MTT) cytotoxic assay. The extracts exhibited antioxidant activity as measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. methanol extract reached the maximal inhibition of 77 ± 10% at 500 µg/mL, and water extract led to 59 ± 3% inhibition at the same concentration. These findings indicate that possesses antidiabetic activity in part by scavenging the oxidants and enhancing GLUT4 translocation to the PM in skeletal muscle.