Effects of Lespedeza Bicolor Extract on Regulation of AMPK Associated Hepatic Lipid Metabolism in Type 2 Diabetic Mice

Lespedeza bicolor (LB) is one of the ornamental plants used for the treatment of inflammation caused by oxidative damage. However, its beneficial effects on hyperglycemia-induced hepatic damage and the related molecular mechanisms remain unclear. We hypothesized that Lespedeza bicolor extract (LBE) would attenuate hyperglycemia-induced liver injury in type 2 diabetes mellitus (T2DM). Diabetes was induced by a low dosage of streptozotocin (STZ) injection (30 mg/kg) with a high fat diet in male C57BL/6J mice. LBE was administered orally at 100 mg/kg or 250 mg/kg for 12 weeks. LBE supplementation regardless of dosage ameliorated plasma levels of hemoglobin A1c (HbA1c) in diabetic mice. Moreover, both LBE supplementations upregulated AMP-activation kinase (AMPK), which may activate sirtuin1 (SIRT) associated pathway accompanied by decreased lipid synthesis at low dose of LBE supplementation. These changes were in part explained by reduced protein levels of oxidative stress (nuclear factor erythroid 2-related factor 2 (Nrf2) and catalase), inflammation (nuclear factor kappa B (NF-κB), interleukin-1β (IL-1β), interleukin-6 (IL-6), and nitric oxide synthases (iNOS)), and fibrosis (α-smooth muscle actin (α-SMA) and protein kinase C (PKC)) in diabetic liver. Taken together, LBE might be a potential nutraceutical to ameliorate hepatic damage by regulation of AMPK associated pathway via oxidative stress, inflammation, and fibrosis in T2DM.