Ginsenoside Rb1 enhances atherosclerotic plaque stability by skewing macrophages to the M2 phenotype

甘露糖受体 巨噬细胞极化 巨噬细胞 M2巨噬细胞 炎症 STAT6 白细胞介素6 免疫学 化学 细胞因子 生物 白细胞介素4 体外 生物化学
作者
Xue Zhang,Minghao Liu,Li Qiao,Xinyu Zhang,Xiaoling Liu,Mei Dong,Hongji Dai,Mei N,Xiaorong Luan,Jun Guan,Huixia Lu
出处
期刊:Journal of Cellular and Molecular Medicine [Wiley]
卷期号:22 (1): 409-416 被引量:65
标识
DOI:10.1111/jcmm.13329
摘要

Abstract Atherosclerosis ( AS ) is characterized as progressive arterial plaque, which is easy to rupture under low stability. Macrophage polarization and inflammation response plays an important role in regulating plaque stability. Ginsenoside Rb1 (Rb1), one of the main active principles of Panax Ginseng , has been found powerful potential in alleviating inflammatory response. However, whether Rb1 could exert protective effects on AS plaque stability remains unclear. This study investigated the role of Rb1 on macrophage polarization and atherosclerotic plaque stability using primary peritoneal macrophages isolated from C57 BL /6 mice and AS model in ApoE −/− mice. In vitro , Rb1 treatment promoted the expression of arginase‐I (Arg‐I) and macrophage mannose receptor ( CD 206), two classic M2 macrophages markers, while the expression of iNOS (M1 macrophages) was decreased. Rb1 increased interleukin‐4 ( IL ‐4) and interleukin‐13 ( IL ‐13) secretion in supernatant and promoted STAT 6 phosphorylation. IL ‐4 and/or IL ‐13 neutralizing antibodies and leflunomide, a STAT 6 inhibitor attenuated the up‐regulation of M2 markers induced by Rb1. In vivo , the administration of Rb1 promoted atherosclerotic lesion stability, accompanied by increased M2 macrophage phenotype and reduced MMP ‐9 staining. These data suggested that Rb1 enhanced atherosclerotic plaque stability through promoting anti‐inflammatory M2 macrophage polarization, which is achieved partly by increasing the production of IL ‐4 and/or IL ‐13 and STAT 6 phosphorylation. Our study provides new evidence for possibility of Rb1 in prevention and treatment of atherosclerosis.
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