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Acta Biochim Biophys Sin (Shanghai). 2014 Sep;46(9):738-48. doi: 10.1093/abbs/gmu065.

Hypoglycemic effect of catalpol on high-fat diet/streptozotocin-induced diabetic mice by increasing skeletal muscle mitochondrial biogenesis.

Author information

1
Jiangsu Center of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
2
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.
3
Jiangsu Center of Drug Screening, China Pharmaceutical University, Nanjing 210009, China Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, China.
4
Pharmacy Department, Shaanxi Cancer Hospital, Xi'an 710061, China.
5
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.
6
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.

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.

KEYWORDS:

catalpol; hypoglycemia; mitochondrial biogenesis; muscle

PMID:
25178463
DOI:
10.1093/abbs/gmu065
[Indexed for MEDLINE]

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