title: Hypoglycemic effect of catalpol on high-fat diet/streptozotocin-induced diabetic mice by increasing skeletal muscle mitochondrial biogenesis.
abstract: Catalpol, an iridoid glycoside, exists in the root of Radix Rehmanniae. Some studies have shown that catalpol has a remarkable hypoglycemic effect in the streptozotocin-induced diabetic model, but the underlying mechanism for this effect has not been fully elucidated. Because mitochondrial dysfunction plays a vital role in the pathology of diabetes and because improving mitochondrial function may offer a new approach for the treatment of diabetes, this study was designed. Catalpol was orally administered together with metformin to high-fat diet/streptozotocin (HFD/STZ)-induced diabetic mice daily for 4 weeks. Body weight (BW), fasting blood glucose (FBG) level, and glucose disposal (IPGTT) were measured during or after the treatment. The results showed a dose-dependent reduction of FBG level with no apparent changes in BW through four successive weeks of catalpol administration. Catalpol treatment substantially reduced serum total cholesterol and triglyceride levels in the diabetic mice. In addition, catalpol efficiently increased mitochondrial ATP production and reversed the decrease of mitochondrial membrane potential and mtDNA copy number in skeletal muscle tissue. Furthermore, catalpol (200 mg/kg) rescued mitochondrial ultrastructure in skeletal muscle, as detected with transmission electron microscopy. The relative mRNA level of peroxisome proliferator-activated receptor gamma co-activator 1 (PGC1) α was significantly decreased in muscle tissue of diabetic mice, while this effect was reversed by catalpol, resulting in a dose-dependent up-regulation. Taken together, we found that catalpol was capable of lowering FBG level via improving mitochondrial function in skeletal muscle of HFD/STZ-induced diabetic mice.
authors.affiliation: Jiangsu Center of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.affiliation: Jiangsu Center of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Zhimeng
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Jiangsu Center of Drug Screening, China Pharmaceutical University, Nanjing 210009, China Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Zhenzhou
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Jiangsu Center of Drug Screening, China Pharmaceutical University, Nanjing 210009, China Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Sun
authors.affiliation: Jiangsu Center of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Jinzi
authors.initials: J
authors.lastname: Ji
authors.affiliation: Jiangsu Center of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Jingshan
authors.initials: J
authors.lastname: Miao
authors.affiliation: Pharmacy Department, Shaanxi Cancer Hospital, Xi'an 710061, China.
authors.forename: Xueji
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Jiangsu Center of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Li
authors.affiliation: Jiangsu Center of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Huang
authors.affiliation: Jiangsu Center of Drug Screening, China Pharmaceutical University, Nanjing 210009, China Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, China wangtao1331@126.com lyzhang@cpu.edu.cn.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Jiangsu Center of Drug Screening, China Pharmaceutical University, Nanjing 210009, China State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China wangtao1331@126.com lyzhang@cpu.edu.cn.
authors.forename: Luyong
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001483:Base Sequence; D001835:Body Weight / Q000187:drug effects; D017931:DNA Primers; D004272:DNA, Mitochondrial / Q000378:metabolism; D059305:Diet, High-Fat; D005951:Glucose Tolerance Test; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008687:Metformin / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D013311:Streptozocin
chemical_list: D017931:DNA Primers; D004272:DNA, Mitochondrial; D007004:Hypoglycemic Agents; D000644:Quaternary Ammonium Compounds; D013311:Streptozocin; C031490:catamine AB; D008687:Metformin
keywords: catalpol; hypoglycemia; mitochondrial biogenesis; muscle