Li Xia, Xu Zhimeng, Jiang Zhenzhou, Sun Lixin, Ji Jinzi, Miao Jingshan, Zhang Xueji, Li Xiaojie, Huang Shan, Wang Tao, Zhang Luyong
Jiangsu Center of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
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.
Acta Biochim Biophys Sin (Shanghai). 2014 Sep;46(9):738-48. doi: 10.1093/abbs/gmu065.
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.
梓醇是一种环烯醚萜苷，存在于地黄根中。一些研究表明，梓醇在链脲佐菌素诱导的糖尿病模型中具有显著的降血糖作用，但其作用的潜在机制尚未完全阐明。由于线粒体功能障碍在糖尿病病理过程中起着至关重要的作用，且改善线粒体功能可能为糖尿病治疗提供新方法，因此设计了本研究。将梓醇与二甲双胍一起每日口服给予高脂饮食/链脲佐菌素（HFD/STZ）诱导的糖尿病小鼠，持续4周。在治疗期间或治疗后测量体重（BW）、空腹血糖（FBG）水平和葡萄糖处置（IPGTT）。结果显示，连续四周给予梓醇后，FBG水平呈剂量依赖性降低，而BW无明显变化。梓醇治疗显著降低了糖尿病小鼠的血清总胆固醇和甘油三酯水平。此外，梓醇有效增加了线粒体ATP生成，并逆转了骨骼肌组织中线粒体膜电位和mtDNA拷贝数的降低。此外，通过透射电子显微镜检测发现，梓醇（200mg/kg）挽救了骨骼肌中的线粒体超微结构。糖尿病小鼠肌肉组织中过氧化物酶体增殖物激活受体γ共激活因子1（PGC1）α的相对mRNA水平显著降低，而梓醇可逆转这种作用，导致其呈剂量依赖性上调。综上所述，我们发现梓醇能够通过改善HFD/STZ诱导的糖尿病小鼠骨骼肌中的线粒体功能来降低FBG水平。
