A metabolite of Danshen formulae attenuates cardiac fibrosis induced by isoprenaline, via a NOX2/ROS/p38 pathway

British Journal of Pharmacology
Qian YinZijian Li

Abstract

Cardiac 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 β-adrenoceptor agonist, isoprenaline, and its underlying mechanisms. Identification 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. IDHP attenuated β-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 path...Continue Reading

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Citations

Dec 3, 2015·British Journal of Pharmacology·Xin WangBaofeng Yang
Apr 21, 2016·Journal of Assisted Reproduction and Genetics·Tian XiaChune Chao
Mar 2, 2018·Antioxidants & Redox Signaling·Paul J M WijnkerJolanda van der Velden
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Jun 13, 2020·BMC Complementary Medicine and Therapies·Hongjie WangSiyun Niu
Feb 2, 2021·Chemical & Pharmaceutical Bulletin·Xiaoling WangHan Xie
Dec 19, 2020·Biochemical and Biophysical Research Communications·Qiuhuan YuanYuguo Chen
May 18, 2021·Biotechnology and Applied Biochemistry·Rajendran HarishKumar, Chinnadurai Immanuel Selvaraj
Aug 1, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yuqian ZhaoXinsheng Yao

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