title: Mitochondrial fusion/fission process involved in the improvement of catalpol on high glucose-induced hepatic mitochondrial dysfunction.
abstract: Catalpol, an iridoid glycoside, has been shown to exert hypoglycemic effect by rescuing mitochondrial function, but the detailed mechanism remains unclear yet. In this study, the effect and mechanism of catalpol on the hepatic mitochondria under diabetic conditions were further examined. Oral administration of catalpol significantly reduced the blood glucose, triglyceride, and cholesterol levels in high-fat diet- and streptozotocin-induced diabetic mice. Additionally, catalpol attenuated the decrease in liver mitochondrial ATP content resulting from diabetes. Furthermore, the number of mitochondria possessing a long size was increased in catalpol-treated mice. Interestingly, the catalpol-induced recovery of mitochondrial function was associated with decreased fission protein 1 and dynamin-related protein 1 expression as well as increased mitofusin 1 expression in the liver. In HepG2 cells, catalpol alleviated the decrease of ATP content and mitochondrial membrane potential, and the increase of reactive oxygen species formation induced by high glucose. MitoTracker Green stain shows that the tubular feature of mitochondria was maintained when cells were treated with catalpol. Catalpol also decreased fission protein 1 and dynamin-related protein 1 expression and increased mitofusin 1 expression in HepG2 cells. The present results suggest that catalpol can ameliorate hepatic mitochondrial dysfunction under a diabetic state, and this may be related to its regulation of mitochondrial fusion and fission events.
authors.affiliation: Jiangsu Center of Drug Screening, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
authors.forename: Zhimeng
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Jiangsu Center of Drug Screening, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Luyong
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Jiangsu Center of Drug Screening, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Li
authors.affiliation: Jiangsu Center of Drug Screening, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China Jiangsu Center for Pharmacodynamics Research and Evaluation, 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, 24 Tong Jia Xiang, 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, 24 Tong Jia Xiang, Nanjing 210009, China.
authors.forename: Guolin
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Qinghai Yangzong Pharmaceutial Co., Ltd, Xining 810003, China.
authors.forename: Guohua
authors.initials: G
authors.lastname: Zhou
authors.affiliation: Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China.
authors.forename: Heran
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Jiangsu Center of Drug Screening, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, China shangjing21cn@163.com wangtao1331@126.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Shang
authors.affiliation: Jiangsu Center of Drug Screening, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, China shangjing21cn@163.com wangtao1331@126.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000503:physiopathology; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology*; D057888:Iridoid Glucosides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D013311:Streptozocin
chemical_list: D004272:DNA, Mitochondrial; D057888:Iridoid Glucosides; C078040:catalpol; D013311:Streptozocin; D000255:Adenosine Triphosphate; D005947:Glucose
keywords: catalpol; diabetic; fusion/fission; liver; mitochondria