Ganoderic acids alleviate atherosclerosis by inhibiting macrophage M1 polarization via TLR4/MyD88/NF-κB signaling pathway

被引：5

作者：

Quan, Ya-zhu ^{[1
]}

Ma, Ang ^{[1
,2
]}

Ren, Chao-qun ^{[1
]}

An, Yong-pan ^{[1
]}

Qiao, Pan-shuang ^{[1
]}

Gao, Cai ^{[1
]}

Zhang, Yu-kun ^{[1
,3
]}

Li, Xiao-wei ^{[1
,4
]}

Lin, Si -mei ^{[1
]}

Li, Nan-nan ^{[1
]}

Chen, Di-long ^{[3
]}

Pan, Yan ^{[1
]}

Zhou, Hong ^{[1
]}

Lin, Dong-mei ^{[5
]}

Lin, Shu-qian ^{[5
]}

Li, Min ^{[1
]}

Yang, Bao-xue ^{[1
,6
]}

机构：

[1] Peking Univ, Sch Basic Med Sci, Dept Pharmacol, State Key Lab Vasc Homeostasis & Remodeling, Beijing 100191, Peoples R China

[2] China Acad Chinese Med Sci, Inst Chinese Materia Med, Artemisinin Res Ctr, Beijing 100007, Peoples R China

[3] Chongqing Three Gorges Med Coll, Chongqing Key Lab Dev & Utilizat Genuine Med Mat T, Chongqing 404020, Peoples R China

[4] China Resources Pharmaceut Grp Ltd, Beijing 100000, Peoples R China

[5] Fujian Agr & Forestry Univ, China Natl Engn Res Ctr JUNCAO Technol, Fuzhou 350002, Peoples R China

[6] Peking Univ, Sch Basic Med Sci, Dept Pharmacol, 38 Xueyuan Rd, Beijing 100191, Peoples R China

来源：

ATHEROSCLEROSIS | 2024年 / 391卷

基金：

中国国家自然科学基金; 北京市自然科学基金;

关键词：

Ganoderma lucidum; Ganoderic acid; Atherosclerosis; Macrophage polarization; Inflammation; Nuclear factor-kappa B; ACTIVATION; PHARMACOLOGY; METABOLISM;

D O I：

10.1016/j.atherosclerosis.2024.117478

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background and aims: Atherosclerosis (AS) is a chronic inflammatory disease characterized by lipid infiltration and plaque formation in blood vessel walls. Ganoderic acids (GA), a class of major bioactive compounds isolated from the Chinese traditional medicine Ganoderma lucidum, have multiple pharmacological activities. This study aimed to determine the anti-atherosclerotic effect of GA and reveal the pharmacological mechanism. Methods: ApoE-/- mice were fed a high -cholesterol diet and treated with GA for 16 weeks to induce AS and identify the effect of GA. Network pharmacological analysis was performed to predict the anti-atherosclerotic mechanisms. An in vitro cell model was used to explore the effect of GA on macrophage polarization and the possible mechanism involved in bone marrow dereived macrophages (BMDMs) and RAW264.7 cells stimulated with lipopolysaccharide or oxidized low-density lipoprotein. Results: It was found that GA at 5 and 25 mg/kg/d significantly inhibited the development of AS and increased plaque stability, as evidenced by decreased plaque in the aorta, reduced necrotic core size and increased collagen/lipid ratio in lesions. GA reduced the proportion of M1 macrophages in plaques, but had no effect on M2 macrophages. In vitro experiments showed that GA (1, 5, 25 mu g/mL) significantly decreased the proportion of CD86+ macrophages and the mRNA levels of IL -6, IL-1 beta, and MCP-1 in macrophages. Experimental results showed that GA inhibited M1 macrophage polarization by regulating TLR4/MyD88/NF-kappa B signaling pathway. Conclusions: This study demonstrated that GA play an important role in plaque stability and macrophage polarization. GA exert the anti-atherosclerotic effect partly by regulating TLR4/MyD88/NF-kappa B signaling pathways to inhibit M1 polarization of macrophages. Our study provides theoretical basis and experimental data for the pharmacological activity and mechanisms of GA against AS.

引用

页数：12

共 39 条

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