Artesunate attenuated progression of atherosclerosis lesion formation alone or combined with rosuvastatin through inhibition of pro-inflammatory cytokines and pro-inflammatory chemokines.

Abstract

BACKGROUNDS:

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.

PURPOSE:

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.

CONCLUSION:

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.

• Authors: Weiwei Jiang, Yanyan Cen, Yi Song, Pan Li, Rongxin Qin, Chao Liu, Yibo Zhao, Jiang Zheng, Hong Zhou
• Journal: Phytomedicine : international journal of phytotherapy and phytopharmacology (Phytomedicine) Vol. 23 Issue 11 Pg. 1259-66 (Oct 15 2016) ISSN: 1618-095X [Electronic] Germany
• PMID: 27316397 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier GmbH. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Artemisinins
• Chemokine CCL2
• Cytokines
• Drugs, Chinese Herbal
• Plant Extracts
• Rosuvastatin Calcium

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Artemisinins (pharmacology, therapeutic use)
• Atherosclerosis (chemically induced, drug therapy, physiopathology)
• Chemokine CCL2 (metabolism)
• Cytokines (metabolism)
• Disease Progression
• Drugs, Chinese Herbal (pharmacology, therapeutic use)
• Humans
• Inflammation (drug therapy)
• Male
• Mice
• Mice, Knockout
• Plant Extracts (pharmacology, therapeutic use)
• Rosuvastatin Calcium (adverse effects)