title: Salidroside stimulates mitochondrial biogenesis and protects against H₂O₂-induced endothelial dysfunction.
abstract: Salidroside (SAL) is an active component of Rhodiola rosea with documented antioxidative properties. The purpose of this study is to explore the mechanism of the protective effect of SAL on hydrogen peroxide- (H2O2-) induced endothelial dysfunction. Pretreatment of the human umbilical vein endothelial cells (HUVECs) with SAL significantly reduced the cytotoxicity brought by H2O2. Functional studies on the rat aortas found that SAL rescued the endothelium-dependent relaxation and reduced superoxide anion (O2(∙-)) production induced by H2O2. Meanwhile, SAL pretreatment inhibited H2O2-induced nitric oxide (NO) production. The underlying mechanisms involve the inhibition of H2O2-induced activation of endothelial nitric oxide synthase (eNOS), adenosine monophosphate-activated protein kinase (AMPK), and Akt, as well as the redox sensitive transcription factor, NF-kappa B (NF- κ B). SAL also increased mitochondrial mass and upregulated the mitochondrial biogenesis factors, peroxisome proliferator-activated receptor gamma-coactivator-1alpha (PGC-1 α ), and mitochondrial transcription factor A (TFAM) in the endothelial cells. H2O2-induced mitochondrial dysfunction, as demonstrated by reduced mitochondrial membrane potential (Δ ψ m) and ATP production, was rescued by SAL pretreatment. Taken together, these findings implicate that SAL could protect endothelium against H2O2-induced injury via promoting mitochondrial biogenesis and function, thus preventing the overactivation of oxidative stress-related downstream signaling pathways.
authors.affiliation: Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China ; The Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation of Hubei Province, Wuhan 430030, China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Xing
authors.affiliation: Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China ; The Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation of Hubei Province, Wuhan 430030, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China ; The Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation of Hubei Province, Wuhan 430030, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China ; The Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation of Hubei Province, Wuhan 430030, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Bian
authors.affiliation: Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China ; The Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation of Hubei Province, Wuhan 430030, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China ; The Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation of Hubei Province, Wuhan 430030, China.
authors.forename: Jiangyang
authors.initials: J
authors.lastname: Chi
authors.affiliation: Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China ; The Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation of Hubei Province, Wuhan 430030, China.
authors.forename: Gao
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China ; The Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation of Hubei Province, Wuhan 430030, China.
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China ; The Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation of Hubei Province, Wuhan 430030, China.
authors.forename: Si
authors.initials: S
authors.lastname: Jin
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005960:Glucosides / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010636:Phenols / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D029771:Rhodiola / Q000737:chemistry / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D005960:Glucosides; D016328:NF-kappa B; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010636:Phenols; C501429:Ppargc1a protein, rat; D014157:Transcription Factors; D006861:Hydrogen Peroxide; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases; C009172:rhodioloside