Artesunate attenuated progression of atherosclerosis lesion formation alone or combined with rosuvastatin through inhibition of pro-inflammatory cytokines and pro-inflammatory chemokines.
BACKGROUND
Inflammation plays an important role in all stages of atherosclerosis, but little is known about the therapeutic effects of quenching inflammation in atherosclerotic lesions formation.


OBJECTIVE
Herein, the effect of artesunate, a derivant from artemisinin from the traditional Chinese herb sweet wormwood, could attenuate the progression of atherosclerosis lesion formation alone or combined with rosuvastatin in Western-type diet (WD) fed ApoE(-/-) mice, and explored its possible mechanisms.


METHODS
The methods such as ELISA for plasma lipids and cytokines analyses, qRT-PCR and western blot for mRNA and protein expressions, and MTT assay for human umbilical vein endothelial cells (HUVECs) viability were used for in vivo and in vitro experiments.


RESULTS
Artesunate could attenuate the progression of atherosclerosis lesion formation alone or combined with rosuvastatin in WD fed ApoE(-/-) mice without changes in food uptake, body weight and plasma lipids level, but with a significant reduction of pro-inflammatory cytokine, such as TNF-α and IL-6. Furthermore, artesunate could down-regulate the pro-inflammatory chemokines such as IL-8 and MCP-1 in aorta of mice. Besides, artesunate didn't influence IL-8 and MCP-1 secretion in HUVECs up-regulated by TNF-α, but inhibited IL-8 and MCP-1 secretion up-regulated by LPS.


CONCLUSIONS
AS attenuated progression of atherosclerosis lesion formation alone or combined with rosuvastatin through anti-inflammatory effect, resulting in down-regulation of TNF-α and IL-6, and further down-regulating IL-8 and MCP-1 expressions in aorta of WD fed ApoE(-/-) mice. Rosuvastatin combined with artesunate could more effectively attenuate the progression of atherosclerosis lesions than when treated by one of them, demonstrating that lipid-lowering agents combined with anti-inflammatory agents could provide the greater benefit for cardiovascular disease patients. Artesunate is worth further investigating as a candidate drug for the treatment of atherosclerosis.
Department of Pharmacology, College of Medicine, The Third Military Medical University, Chongqing 400038, P. R. China.
Weiwei
W
Jiang
Department of Pharmacology, College of Medicine, The Third Military Medical University, Chongqing 400038, P. R. China.
Yanyan
Y
Cen
Department of Pharmacology, College of Medicine, The Third Military Medical University, Chongqing 400038, P. R. China.
Yi
Y
Song
Department of Pharmacology, College of Medicine, The Third Military Medical University, Chongqing 400038, P. R. China.
Pan
P
Li
Department of Pharmacology, College of Medicine, The Third Military Medical University, Chongqing 400038, P. R. China.
Rongxin
R
Qin
Department of Pharmacology, College of Medicine, The Third Military Medical University, Chongqing 400038, P. R. China.
Chao
C
Liu
Department of Pharmacology, College of Medicine, The Third Military Medical University, Chongqing 400038, P. R. China.
Yibo
Y
Zhao
Medical Research Center, Southwestern Hospital, The Third Military Medical University, Chongqing 400038, P. R. China.
Jiang
J
Zheng
Department of Pharmacology, College of Medicine, The Third Military Medical University, Chongqing 400038, P. R. China. Electronic address: zhouh64@163.com.
Hong
H
Zhou
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D037621:Artemisinins / Q000494:pharmacology* / Q000627:therapeutic use; D050197:Atherosclerosis / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology; D018932:Chemokine CCL2 / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D018450:Disease Progression; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D000068718:Rosuvastatin Calcium / Q000009:adverse effects*
D000893:Anti-Inflammatory Agents; D037621:Artemisinins; D018932:Chemokine CCL2; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; D000068718:Rosuvastatin Calcium
Artesunate; Atherosclerosis; Inflammation; MCP-1; TNF-α