Artemisia annua L. Extracts Improved Insulin Resistance via Changing Adiponectin, Leptin and Resistin Production in HFD/STZ Diabetic Mice

OBJECTIVES: Insulin resistance (IR) is major cause of type 2 diabetes (T2D), and adipokines (e.g., adiponectin, leptin, and resistin) play an important role in insulin sensitivity. Medicinal plants are frequently used for T2D treatment. This study investigates the effect of Artemisia annua L. (AA) extracts on adipokines in mice with high-fat-diet (HFD)/streptozotocin (STZ)-induced T2D. METHODS: We divided 60 mice into 12 groups (n = 5 per group) control, untreated T2D, treated T2D, and 9 other groups. T2D was induced in all groups, except controls, by 8 weeks of HFD and STZ injection. The treated T2D group was administered 250 mg/kg of metformin (MTF), while the nine other groups were treated with 100, 200, and 400 mg/kg of hot-water extract (HWE), cold-water extract (CWE), and alcoholic extract (ALE) of AA (daily oral gavage) along with 250 mg/kg of MTF for 4 weeks. The intraperitoneal glucose tolerance test (IPGTT) was performed, and the homeostasis model assessment of adiponectin (HOMA-AD) index and blood glucose and serum insulin, leptin, adiponectin, and resistin levels were measured. RESULTS: Similar to MTF, all three types of AA extracts (HWEs, CWEs, and ALEs) significantly (p < 0.0001) decreased the area under the curve (AUC) of glucose during the IPGTT, the HOMA-AD index, blood glucose levels, and serum insulin, leptin, and resistin levels and increased serum adiponectin levels in the MTF group compared to the T2D group (p < 0.0001). The HWEs affected adipokine release, while the CWEs and ALEs decreased leptin and resistin production. CONCLUSION: Water and alcoholic AA extracts have an antihyperglycemic and antihyperinsulinemic effect on HFD/STZ diabetic mice. In addition, they decrease IR by reducing leptin and resistin production and increasing adiponectin secretion from adipocytes.