1. Academic Validation
  2. Antiatherosclerotic effect of dehydrocorydaline on ApoE-/- mice: inhibition of macrophage inflammation

Antiatherosclerotic effect of dehydrocorydaline on ApoE-/- mice: inhibition of macrophage inflammation

  • Acta Pharmacol Sin. 2022 Jun;43(6):1408-1418. doi: 10.1038/s41401-021-00769-3.
Bin Wen  # 1 Yuan-Ye Dang  # 1 Su-Hua Wu 1 Yi-Min Huang 1 Kong-Yang Ma 2 Yi-Ming Xu 3 Xi-Long Zheng 4 Xiao-Yan Dai 5
Affiliations

Affiliations

  • 1 Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China.
  • 2 China Centre for Infection and Immunity Studies (CIIS), School of Medicine, Sun Yat-sen University, Shenzhen, 518107, China.
  • 3 School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, China.
  • 4 Department of Biochemistry & Molecular Biology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
  • 5 Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, China. xdai@gzhmu.edu.cn.
  • # Contributed equally.
Abstract

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.

Keywords

atherosclerosis; dehydrocorydaline; inflammation; macrophage.

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