title: Tetramethylpyrazine ameliorates high glucose-induced endothelial dysfunction by increasing mitochondrial biogenesis.
abstract: Tetramethylpyrazine (TMP) is an active compound isolated from a Chinese herbal prescription that is widely used in traditional Chinese medicine for the treatment of inflammatory and cardiovascular diseases. We have previously reported that TMP acts as a potent antioxidant protecting endothelial cells against high glucose-induced damages. However, the molecular mechanism responsible for the antioxidant effect of TMP remains to be elucidated. In this study, we show that TMP increases nitric oxide production in endothelial cells and promotes endothelium-dependent relaxation in rate aortic rings. The antioxidant effect of TMP appears attributable to its ability to activate the mitochondrial biogenesis, as reflected in an up-regulation of complex III and amelioration of mitochondrial membrane potential. Furthermore, TMP is able to reverse high glucose-induced suppression of SIRT1 and the biogenesis-related factors, including PGC-1α, NRF1 and TFAM, suggesting a new molecular mechanism underlying the protective effect of TMP on the endothelium.
authors: Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.
authors: Qiong
authors: Q
authors: Xu
authors: Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.
authors: Pu
authors: P
authors: Xia
authors: The Key Laboratory of Molecular Medicine, Ministry of Education, Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, China.
authors: Xi
authors: X
authors: Li
authors: Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.
authors: Wei
authors: W
authors: Wang
authors: Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, United States of America.
authors: Zhenqi
authors: Z
authors: Liu
authors: Department of Endocrinology and Metabolism, Zhongshan Hospital, Fudan University, Shanghai, China.
authors: Xin
authors: X
authors: Gao
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D014450:Electron Transport Complex III / Q000235:genetics; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D008516:Medicine, Chinese Traditional; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D063269:Mitochondrial Turnover / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism*; D011719:Pyrazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D011719:Pyrazines; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D014450:Electron Transport Complex III; D005947:Glucose; C017953:tetramethylpyrazine