Open AccessGinsenoside Rb1 enhances atherosclerotic plaque stability by skewing macrophages to the M2 phenotype
Author(s) -
Zhang Xue,
Liu Minghao,
Qiao Lei,
Zhang Xinyu,
Liu Xiaoling,
Dong Mei,
Dai Hongyan,
Ni Mei,
Luan Xiaorong,
Guan Jun,
Lu Huixia
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13329
Subject(s) - mannose receptor , macrophage polarization , macrophage , inflammation , m2 macrophage , interleukin 6 , chemistry , immunology , biology , in vitro , biochemistry
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.