title: Cryptotanshinone attenuates cardiac fibrosis via downregulation of COX-2, NOX-2, and NOX-4.
abstract: Cryptotanshinone (CTS), a bioactive constituent extracted from a Chinese traditional herb Danshen (Salvia miltiorrhiza), demonstrates multiple protective effects against cardiovascular diseases. The present study was designed to explore the effects of CTS in vitro by cultured adult rat cardiac fibroblasts stimulated with angiotensin II (Ang II) and in vivo by rats with acute myocardial infarction. Our data showed that in cardiac fibroblasts, CTS attenuated Ang II-induced upregulation of fibronectin, connective tissue growth factor, cyclooxygenase-2, and normalized Ang II-induced upregulation of extracellular signal-regulated kinases 1/2 (ERK1/2). Meanwhile, CTS depressed the Ang II-stimulated upregulation of NAD(P)H oxidase 2 and 4 (NOX-2 and NOX-4) and reactive oxygen species production. Similar results were observed in acute myocardial infarction rats with oral administration of CTS, which relieved the pathological changes accompanying myocardial infarction. In conclusion, CTS may exert antifibrotic effects in vitro by inhibiting Ang II-induced extracellular signal-regulated kinases 1/2 phosphorylation and the expression of cyclooxygenase-2, NOX-2, and NOX-4, and also improved the pathological changes and relieved cardiac fibrosis in vivo.
authors.affiliation: *Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China; and †Cardiovascular and Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
authors.forename: Yunzi
authors.initials: Y
authors.lastname: Ma
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Zhongbao
authors.initials: Z
authors.lastname: Yue
authors.forename: Jinlei
authors.initials: J
authors.lastname: Guo
authors.forename: Suowen
authors.initials: S
authors.lastname: Xu
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Jia
authors.forename: Na
authors.initials: N
authors.lastname: Yu
authors.forename: Boyu
authors.initials: B
authors.lastname: Zhang
authors.forename: Shenglan
authors.initials: S
authors.lastname: Liu
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.forename: Weiwei
authors.initials: W
authors.lastname: Shao
authors.forename: Shaorui
authors.initials: S
authors.lastname: Chen
authors.forename: Peiqing
authors.initials: P
authors.lastname: Liu
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage; D000818:Animals; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology; D005355:Fibrosis; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000235:genetics; D010616:Phenanthrenes / Q000302:isolation & purification / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D027561:Salvia miltiorrhiza / Q000737:chemistry; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D008562:Membrane Glycoproteins; D010616:Phenanthrenes; D000804:Angiotensin II; C037886:cryptotanshinone; D051546:Cyclooxygenase 2; C500593:Cybb protein, rat; D000074662:NADPH Oxidase 2; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498911:Nox4 protein, rat