Kuiniu Zhu1, Zhaoqing Meng2, Yushan Tian3, Rui Gu4, Zhongkun Xu4, Hui Fang4, Wenjun Liu4, Wenzhe Huang4, Gang Ding4, Wei Xiao5. 1. State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process, Jiangsu Kanion Parmaceutical Co., Ltd., Lianyungang, Jiangsu, 222001, China; Huzhou Institute for Food and Drug Control, Huzhou, Zhejiang, 313000, China. 2. State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process, Jiangsu Kanion Parmaceutical Co., Ltd., Lianyungang, Jiangsu, 222001, China; Shandong Hongjitang Pharmaceutical Group Co., Ltd., Jinan, Shandong, 250103, China. 3. Jiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University, Nanjing, 211198, China. 4. State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process, Jiangsu Kanion Parmaceutical Co., Ltd., Lianyungang, Jiangsu, 222001, China. 5. State Key Laboratory of New-tech for Chinese Medicine Pharmaceutical Process, Jiangsu Kanion Parmaceutical Co., Ltd., Lianyungang, Jiangsu, 222001, China. Electronic address: xw_kanion@163.com.
Abstract
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 high-sucrose 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 3β, 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.
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 diabeticrats, 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 diabeticrats were induced by high-fat high-sucrose 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 3β, 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 diabeticrats, which might be largely attributed to the activities of TGCT on inhibitions of oxidative stress and inflammation.