PMID- 34552216
OWN - NLM
STAT- MEDLINE
DCOM- 20220603
LR  - 20230206
IS  - 1745-7254 (Electronic)
IS  - 1671-4083 (Print)
IS  - 1671-4083 (Linking)
VI  - 43
IP  - 6
DP  - 2022 Jun
TI  - Antiatherosclerotic effect of dehydrocorydaline on ApoE(-/-) mice: inhibition of 
      macrophage inflammation.
PG  - 1408-1418
LID - 10.1038/s41401-021-00769-3 [doi]
AB  - 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)-1beta 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-1beta, 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.
CI  - (c) 2021. The Author(s).
FAU - Wen, Bin
AU  - Wen B
AD  - Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, 
      School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 
      511436, China.
FAU - Dang, Yuan-Ye
AU  - Dang YY
AD  - Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, 
      School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 
      511436, China.
FAU - Wu, Su-Hua
AU  - Wu SH
AD  - Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, 
      School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 
      511436, China.
FAU - Huang, Yi-Min
AU  - Huang YM
AD  - Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, 
      School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 
      511436, China.
FAU - Ma, Kong-Yang
AU  - Ma KY
AD  - China Centre for Infection and Immunity Studies (CIIS), School of Medicine, Sun 
      Yat-sen University, Shenzhen, 518107, China.
FAU - Xu, Yi-Ming
AU  - Xu YM
AD  - School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 
      511436, China.
FAU - Zheng, Xi-Long
AU  - Zheng XL
AD  - Department of Biochemistry & Molecular Biology, Cumming School of Medicine, 
      University of Calgary, Calgary, AB, Canada.
FAU - Dai, Xiao-Yan
AU  - Dai XY
AD  - Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, 
      School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 
      511436, China. xdai@gzhmu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20210922
PL  - United States
TA  - Acta Pharmacol Sin
JT  - Acta pharmacologica Sinica
JID - 100956087
RN  - 0 (Alkaloids)
RN  - 0 (Apolipoproteins E)
RN  - 0 (Interleukin-18)
RN  - 0 (Lipopolysaccharides)
RN  - 30045-16-0 (dehydrocorydalin)
SB  - IM
MH  - Alkaloids
MH  - Animals
MH  - Apolipoproteins E
MH  - *Atherosclerosis/metabolism
MH  - Inflammation/metabolism
MH  - *Interleukin-18/metabolism
MH  - Lipopolysaccharides
MH  - Macrophages/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
PMC - PMC9160055
OTO - NOTNLM
OT  - atherosclerosis
OT  - dehydrocorydaline
OT  - inflammation
OT  - macrophage
COIS- The authors declare no competing interests.
EDAT- 2021/09/24 06:00
MHDA- 2022/06/07 06:00
PMCR- 2021/09/22
CRDT- 2021/09/23 06:42
PHST- 2021/04/20 00:00 [received]
PHST- 2021/08/16 00:00 [accepted]
PHST- 2021/09/24 06:00 [pubmed]
PHST- 2022/06/07 06:00 [medline]
PHST- 2021/09/23 06:42 [entrez]
PHST- 2021/09/22 00:00 [pmc-release]
AID - 10.1038/s41401-021-00769-3 [pii]
AID - 769 [pii]
AID - 10.1038/s41401-021-00769-3 [doi]
PST - ppublish
SO  - Acta Pharmacol Sin. 2022 Jun;43(6):1408-1418. doi: 10.1038/s41401-021-00769-3. 
      Epub 2021 Sep 22.