Hypoglycemic and hypolipidemic effects of total glycosides of Cistanche tubulosa in diet/streptozotocin-induced diabetic rats

Ethnopharmacological relevance: Cistanche tubulosa (Schrenk) R. Wight (Orobanchaceae) is a frequently prescribed component in many traditional herbal prescriptions which are used to treat diabetes in China. In recent studies, the antidiabetic activity of Cistanche tubulosa extracts have been confirmed. However, no systematic investigation has been reported on the total glycosides of Cistatnche tubulosa (TGCT). Aim of the study: The present study aimed to investigate the hypoglycemic and hypolipidemic effects of TGCT and the potential mechanisms in diet/streptozotocin (STZ)-induced diabetic rats, and to chemically characterize the main constituents of TGCT. Materials and methods: The major constituents of TGCT were characterized by HPLC/Q-TOF-MS and the analytical quantification was performed with HPLC-DAD. Type 2 diabetic rats were induced by high-fat highsucrose diet (HFSD) and a single injection of STZ (30 mg/kg). TGCT (50 mg/kg, 100 mg/kg and 200 mg/kg) or metformin (200 mg/kg) were orally administered for 6 weeks. Body weight and calorie intake were monitored throughout the experiment. Fasting plasma glucose (FPG), oral glucose tolerance test (OGTT), area under curve of glucose (AUC-G), glycosylated hemoglobin (HbA1c), fasting insulin, serum C-peptide, glycogen content and insulin sensitivity index were tested. The levels of phosphorylated protein kinase B and phosphorylated glycogen synthase kinase 313, the activities of hexokinase and pyruvate kinase were assayed. Meanwhile, the changes in serum lipid profiles, superoxide dismutase, glutathione peroxidase, malondialdehyde and inflammatory factors were measured. Histological of pancreas were also evaluated by haematoxylin-eosin stain. Results: Our investigation revealed the presence of phenylethanoid glycosides (PhGs): echinacoside (500.19 +/- 11.52 mg/g), acteoside (19.13 +/- 1.44 mg/g) and isoacteoside (141.82 +/- 5.78 mg/g) in TGCT. Pharmacological tests indicated that TGCT significantly reversed STZ-induced weight loss (11.1%, 200 mg/kg); decreased FPG (56.4%, 200 mg/kg) and HbA1c (37.4%, 200 mg/kg); ameliorated the OGTT, AUC-G and insulin sensitivity; increased glycogen content (40.8% in liver and 52.6% in muscle, 200 mg/kg) and the activities of carbohydrate metabolizing enzymes; regulated lipid profile changes and the activities of antioxidant enzymes; diminished serum markers of oxidative stress and inflammation in a dose-dependent manner (p < 0.05). Conclusions: This study confirmed that TGCT was an effective nutritional agent for ameliorating hyperglycemia and hyperlipidemia in diet/STZ-induced diabetic rats, which might be largely attributed to the activities of TGCT on inhibitions of oxidative stress and inflammation.