Restoring perturbed oxylipins with Danqi Tongmai Tablet attenuates acute myocardial infarction

doi:10.1016/j.phymed.2021.153616

	Restoring perturbed oxylipins with Danqi Tongmai Tablet attenuates acute myocardial infarction
	Zhi, Haijuan 1; Zhang, Zijia 1,2; Deng, Yanping 1,2; Yan, Bingpeng 1; Li, Zhenwei 1,2; Wu, Wenyong 1,2; Feng, Zijing 1; Lei, Min 1,2; Long, Huali 1,2; Hou, Jinjun 1,2
刊名	PHYTOMEDICINE
	2021-09-01
卷号	90 页码:12
关键词	Acute myocardial infarction Danqi Tongmai tablet In vivo metabolite Oxylipin Arachidonic acid metabolome Homeostasis
ISSN号	0944-7113
DOI	10.1016/j.phymed.2021.153616
通讯作者	Hou, Jinjun(jinjun_hou@simm.ac.cn) ; Guo, Dean(daguo@simm.ac.cn) ; Wu, Wanying(wanyingwu@simm.ac.cn)
英文摘要	Salvianolic acids have a special synergic effect on panax notoginsenosides in acute myocardial infarction (AMI) and have been developed into a new drug as Danqi Tongmai Tablet (DQTT). To explore candidate targets and mechanisms of DQTT on AMI, a network pharmacology-based analysis was performed on absorbed prototype compounds of DQTT in rat plasma. Target prediction from network analysis indicated that the arachidonic acid pathway might contribute to the therapeutic effects of DQTT on AMI, and the regulatory effects on cyclo-oxygenase (COX) and lipoxygenase (LOX) were validated using an oxygen-glucose deprivation/reoxygenation model established on H9c2 cardiomyocytes. To further explore the action mechanisms of DQTT, 38 oxylipins were quantitatively analyzed among high, medium, and low doses of DQTT using a rat AMI model with an ultra high performance liquid chromatograph coupled with a triple quadrupole mass spectrometry (UHPLC-QqQ/MS) detection system. As attenuation was observed in AMI with DQTT treatment, the perturbed arachidonic acid metabolome was partly restored in a dose-dependent fashion with a significant elevation of anti-inflammatory metabolites, while pro-inflammatory lipids were decreased. Cytokine array analysis also supported the anti-inflammatory effects of DQTT, as significant down-regulation of pro-inflammatory cytokines was observed. The analysis of ischemic heart tissues demonstrated that COX and LOX, the inflammation-induced catalytic enzymes of arachidonic acid metabolism, were inhibited on both gene expression and protein level. These results confirmed that DQTT could restore the arachidonic acid metabolome to maintain an anti-inflammatory profile against the ischemic tissue injury and support that DQTT can be a promising medicinal therapy against AMI.
WOS关键词	SOLUBLE EPOXIDE HYDROLASE ; INFLAMMATORY RESPONSE ; THERAPEUTIC TARGET ; LIPID MEDIATORS ; ACID ; CYTOCHROME-P450 ; METABOLOMICS ; ANGIOGENESIS ; ACTIVATION ; RESOLUTION
WOS研究方向	Plant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine
语种	英语
出版者	ELSEVIER GMBH
WOS记录号	WOS:000685219400004
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/297964]
专题	中国科学院上海药物研究所
通讯作者	Hou, Jinjun; Guo, Dean; Wu, Wanying
作者单位	1.Chinese Acad Sci, Shanghai Res Ctr Modernizat Tradit Chinese Med, Natl Engn Lab TCM Standardizat Technol, Shanghai Inst Mat Med, 501 Haike Rd, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, 19A Yuanquan Rd, Beijing 100049, Peoples R China
推荐引用方式 GB/T 7714	Zhi, Haijuan,Zhang, Zijia,Deng, Yanping,et al. Restoring perturbed oxylipins with Danqi Tongmai Tablet attenuates acute myocardial infarction[J]. PHYTOMEDICINE,2021,90:12.
APA	Zhi, Haijuan.,Zhang, Zijia.,Deng, Yanping.,Yan, Bingpeng.,Li, Zhenwei.,...&Wu, Wanying.(2021).Restoring perturbed oxylipins with Danqi Tongmai Tablet attenuates acute myocardial infarction.PHYTOMEDICINE,90,12.
MLA	Zhi, Haijuan,et al."Restoring perturbed oxylipins with Danqi Tongmai Tablet attenuates acute myocardial infarction".PHYTOMEDICINE 90(2021):12.