|A metabolite of Danshen formulae attenuates cardiac fibrosis induced by isoprenaline, via a NOX2/ROS/p38 pathway|
|Yin, Qian1,2,3; Lu, Haiyan1,2,4; Bai, Yajun4; Tian, Aiju1,2; Yang, Qiuxiang1,2,4; Wu, Jimin1,2; Yang, Chengzhi1,2; Fan, Tai-Ping5; Zhang, Youyi1,2; Zheng, Xiaohui4; Zheng, Xiaopu3; Li, Zijian1,2|
|刊名||BRITISH JOURNAL OF PHARMACOLOGY|
|WOS标题词||Science & Technology|
|类目[WOS]||Pharmacology & Pharmacy|
|研究领域[WOS]||Pharmacology & Pharmacy|
|关键词[WOS]||OXIDATIVE STRESS ; REACTIVE OXYGEN ; MYOCARDIAL-INFARCTION ; SALVIA-MILTIORRHIZA ; CELL-PROLIFERATION ; ARRIVE GUIDELINES ; AQUEOUS EXTRACT ; HEART-FAILURE ; NADPH OXIDASE ; CONCISE GUIDE|
Background and PurposeCardiac fibrosis is a common feature of advanced coronary heart disease and is characteristic of heart disease. However, currently available drugs against cardiac fibrosis are still very limited. Here, we have assessed the role of isopropyl 3-(3,4-dihydroxyphenyl)-2-hydroxylpropanoate (IDHP), a new metabolite of Danshen Dripping Pills, in cardiac fibrosis mediated by the -adrenoceptor agonist, isoprenaline, and its underlying mechanisms.
Experimental ApproachIdentification of IDHP was identified by mass spectrometry, and proton and carbon nuclear magnetic resonance spectra. Myocardial collagen was quantitatively assessed with Picrosirius Red staining. Expression of mRNA for collagen was evaluated with real-time PCR. Phosphorylated and total p38 MAPK, NADPH oxidase (NOX) and superoxide dismutase (SOD) were analysed by Western blot. Generation of reactive oxygen species (ROS) generation was evaluated by dihydroethidium (DHE) fluorescent staining. NOX2 was knocked down using specific siRNA.
Key ResultsIDHP attenuated -adrenoceptor mediated cardiac fibrosis in vivo and inhibited isoprenaline-induced proliferation of neonatal rat cardiac fibroblasts (NRCFs) and collagen I synthesis in vitro. Phosphorylation of p38 MAPK, which is an important mediator in the pathogenesis of isoprenaline-induced cardiac fibrosis, was inhibited by IDHP. This inhibition of phospho-p38 by IDHP was dependent on decreased generation of ROS. These effects of IDHP were abolished in NRCFs treated with siRNA for NOX2.
Conclusions and ImplicationsIDHP attenuated the cardiac fibrosis induced by isoprenaline through a NOX2/ROS/p38 pathway. These novel findings suggest that IDHP is a potential pharmacological candidate for the treatment of cardiac fibrosis, induced by -adrenoceptor agonists.
Linked ArticlesThis article is part of a themed section on Chinese Innovation in Cardiovascular Drug Discovery. To view the other articles in this section visit http://dx. doi. org/10.1111/bph. 2015.172. issue-23
|项目编号||2011CB503903 ; 81270157 ; 81471893 ; 81070078 ; 7102158 ; IRT1174 ; 2013KCT-24 ; 2013YQ170525|
|资助机构||National Basic Research Program of China ; National Natural Science Foundation of China ; Beijing Municipal Natural Science Foundation ; Changjiang Scholars and Innovative Research Team in University ; Project for Innovative Research Team of Research and Technology of Shaanxi Province ; National Scientific Instrument and Equipment Development Project of China|
|作者单位||1.Peking Univ, Key Lab Cardiovasc Mol Biol & Regulatory Peptides, Key Lab Mol Cardiovasc Sci, Inst Vasc Med,Minist Hlth,Minist Educ,Hosp 3, Beijing 100191, Peoples R China|
2.Peking Univ, Beijing Key Lab Cardiovasc Receptors Res, Hosp 3, Beijing 100191, Peoples R China
3.Xi An Jiao Tong Univ, Hlth Sci Ctr, Affiliated Hosp 3, Dept Cardiovasc Med, Xian 710049, Peoples R China
4.NW Univ Xian, Key Lab Resource Biol & Biotechnol Western China, Coll Life Sci, Minist Educ, Xian 710069, Peoples R China
5.Univ Cambridge, Dept Pharmacol, Angiogenesis & Chinese Med Lab, Cambridge CB2 1QJ, England
|Yin, Qian,Lu, Haiyan,Bai, Yajun,et al. A metabolite of Danshen formulae attenuates cardiac fibrosis induced by isoprenaline, via a NOX2/ROS/p38 pathway[J]. BRITISH JOURNAL OF PHARMACOLOGY,2015,172(23):5573-5585.|
|APA||Yin, Qian.,Lu, Haiyan.,Bai, Yajun.,Tian, Aiju.,Yang, Qiuxiang.,...&Li, Zijian.(2015).A metabolite of Danshen formulae attenuates cardiac fibrosis induced by isoprenaline, via a NOX2/ROS/p38 pathway.BRITISH JOURNAL OF PHARMACOLOGY,172(23),5573-5585.|
|MLA||Yin, Qian,et al."A metabolite of Danshen formulae attenuates cardiac fibrosis induced by isoprenaline, via a NOX2/ROS/p38 pathway".BRITISH JOURNAL OF PHARMACOLOGY 172.23(2015):5573-5585.|
|Yin_et_al-2015-Briti（1763KB）||期刊论文||作者接受稿||开放获取||CC BY-NC-SA||浏览 请求全文|