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.
Highlights
Atherosclerosis is a leading cause of mortality and morbidity worldwide because of its pathological roles in most cardiovascular diseases (CVDs), such as coronary artery disease, myocardial infarction, and stroke [1]
DHC reduces inflammation in resting and activated bone marrow-derived macrophages (BMDMs) To further confirm the anti-inflammatory effect of DHC, we treated for 12 weeks (Fig. 1b)
Our current study has demonstrated for the first time that DHC ameliorates atherosclerosis in ApoE−/− mice fed a Western diet, accompanied by improved aortic compliance and plaque stability
Summary
Atherosclerosis is a leading cause of mortality and morbidity worldwide because of its pathological roles in most cardiovascular diseases (CVDs), such as coronary artery disease, myocardial infarction, and stroke [1]. The primary antibodies were as follows: CD80 (Abcam, ab238481), iNOS (Thermo Fisher, PA1-036), NLRP3 (Life Science, AG-20B-0014-C100), IL-1β (R&D Systems, AF-401-NA), IL-18 atherosclerotic lesion area, as indicated by H&E staining, the oil red O+ area, and lesion macrophage levels (F4/80+), were significantly smaller in the aortic roots of DHC-treated ApoE−/− mice than in control mice (Fig. 2a–c). I.p. injection of DHC for 1 week significantly reduced TNFα, NLRP3, and IL-18 mRNA levels in the aortas of ApoE−/− mice (Fig. 3c).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
