title: Baicalin attenuates angiotensin II-induced endothelial dysfunction.
abstract: Angiotensin II (Ang II) has been shown to activate multiple downstream pathways resulting in endothelial dysfunction and oxidative stress. Baicalin, a natural flavone, exerts anti-oxidant and anti-apoptotic effects in cardiovascular diseases. In the present study, we hypothesized that baicalin has beneficial effects in Ang II-induced endothelial cells injury. Here, we shown that baicalin improved endothelial fuction impaired by Ang II through promoting endothelial-dependent vasodilation and suppressing the apoptosis of HUVECs in which baicalin decreased the expression of bax and cleaved caspase-3, and increased bcl-2 expression. Additionally, baicalin significantly conversed Ang II to angiotensin-1-7 [Ang-(1-7)] by activating angiotensin-converting enzyme 2 (ACE2) and Mas receptor mRNA expression and protein expression. Moreover, treatment with baicalin significantly reduced cell oxidative damage induced by Ang II through MDA/ROS decrease and NO/T-AOC increase. This antioxidant capacity was related to the increases of PI3K, phosphor-AKT (Ser-473) and phosphor-eNOS (Ser-1177). In conclusion, our results implicate that baicalin could protect endothelial cells from Ang II-induced endothelial dysfunction and oxidative stress via modulating the expression of bax, bcl-2 and cleaved caspase-3, activating ACE2/Ang-(1-7)/Mas axis and up-regulating PI3K/AKT/eNOS pathway.
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing, China. Electronic address: celiawei@126.com.
authors.forename: Xiling
authors.initials: X
authors.lastname: Wei
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing, China. Electronic address: 779190918@qq.com.
authors.forename: Xingyu
authors.initials: X
authors.lastname: Zhu
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing, China. Electronic address: 594432433@qq.com.
authors.forename: Nan
authors.initials: N
authors.lastname: Hu
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing, China. Electronic address: 835699945@qq.com.
authors.forename: Xiuqin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing, China. Electronic address: 1652040223@qq.com.
authors.forename: Tianjiao
authors.initials: T
authors.lastname: Sun
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing, China. Electronic address: jiyangx@126.com.
authors.forename: Jiyang
authors.initials: J
authors.lastname: Xu
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing, China. Electronic address: xh_bian@163.com.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Bian
mesh_terms: D000803:Angiotensin I / Q000819:agonists / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology*; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D010446:Peptide Fragments / Q000819:agonists / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D046509:Tissue Culture Techniques; D014664:Vasodilation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000803:Angiotensin I; D000804:Angiotensin II; D000085962:Angiotensin-Converting Enzyme 2; D053148:Caspase 3; D005419:Flavonoids; D052250:Nitric Oxide Synthase Type III; D010446:Peptide Fragments; D007703:Peptidyl-Dipeptidase A; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C494826:BAX protein, human; C000595707:BCL2 protein, human; C038044:baicalin; C496314:NOS3 protein, human; C000705307:ACE2 protein, human; C000705329:Ace2 protein, rat; C118790:angiotensin I (1-7)
keywords: ACE2/Ang-(1-7)/Mas axis; Angiotensin II; Baicalin; Oxidative stress; PI3K/AKT pathway