Despite improvements in cardiovascular disease(CVD)outcomes by cholesterol-lowering statin therapy,the high rate of CVD is still a great concern worldwide.Dehydrocorydaline(DHC)is an alkaloidal compound isolated from the traditional Chinese herb Corydalis yanhusuo.Emerging evidence shows that DHC has anti-inflammatory and antithrombotic benefits,but whether DHC exerts any antiatherosclerotic effects remains unclear.Our study revealed that intraperitoneal(i.p.)injection of DHC in apolipoprotein E-deficient(ApoE-/-)mice not only inhibited atherosclerosis development but also improved aortic compliance and increased plaque stability.In addition,DHC attenuated systemic and vascular inflammation in ApoE-/-mice.As macrophage inflammation plays an essential role in the pathogenesis of atherosclerosis,we next examined the direct effects of DHC on bone marrow-derived macrophages(BMDMs)in vitro.Our RNA-seq data revealed that DHC dramatically decreased the levels of proinflammatory gene clusters.We verified that DHC significantly downregulated proinflammatory interleukin(IL)-1β and IL-18 mRNA levels in a time-and concentration-dependent manner.Furthermore,DHC decreased lipopolysaccharide(LPS)-induced inflammation in BMDMs,as evidenced by the reduced protein levels of CD80,iNOS,NLRP3,IL-1β,and IL-18.Importantly,DHC attenuated LPS-induced activation of p65 and the extracellular signal-regulated kinase 1/2(ERK1/2)pathway.Thus,we conclude that DHC ameliorates atherosclerosis in ApoE-/-mice by inhibiting inflammation,likely by targeting macrophage p65-and ERK1/2-mediated pathways.

Bin Wen;Yuan-ye Dang;Su-hua Wu;Yi-min Huang;Kong-yang Ma;Yi-ming Xu;Xi-Long Zheng;Xiao-yan Dai

Guangdong Provincial Key Laboratory of Molecular Target&Clinical Pharmacology,School of Pharmaceutical Sciences,Guangzhou Medical University,Guangzhou 511436,China;China Centre for Infection and Immunity Studies(CIIS),School of Medicine,Sun Yat-sen University,Shenzhen 518107,China;School of Basic Medical Sciences,Guangzhou Medical University,Guangzhou 511436,China;Department of Biochemistry&Molecular Biology,Cumming School of Medicine,University of Calgary,Calgary,AB,Canada

中国药理学报（英文版）

[1]Bin Wen;Yuan-ye Dang;Su-hua Wu;Yi-min Huang;Kong-yang Ma;Yi-ming Xu;Xi-Long Zheng;Xiao-yan Dai-.Antiatherosclerotic effect of dehydrocorydaline on ApoE-/-mice:inhibition of macrophage inflammation)[J].中国药理学报（英文版）,2022(06):1408-1418

Antiatherosclerotic,dehydrocorydaline,Dehydrocorydaline,alkaloidal,antiatherosclerotic

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