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

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.

• Authors: Bin Wen, Yuan-Ye Dang, Su-Hua Wu, Yi-Min Huang, Kong-Yang Ma, Yi-Ming Xu, Xi-Long Zheng, Xiao-Yan Dai
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 43 Issue 6 Pg. 1408-1418 (Jun 2022) ISSN: 1745-7254 [Electronic] United States
• PMID: 34552216 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s).

Chemical References

• Alkaloids
• Apolipoproteins E
• Interleukin-18
• Lipopolysaccharides
• dehydrocorydalin

Topics

• Alkaloids
• Animals
• Apolipoproteins E
• Atherosclerosis (metabolism)
• Inflammation (metabolism)
• Interleukin-18 (metabolism)
• Lipopolysaccharides
• Macrophages (metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout