Schisandrin B alleviates angiotensin II-induced cardiac inflammatory remodeling by inhibiting the recruitment of MyD88 to TLRs in mouse cardiomyocytes

被引：1

作者：

Xu, Sujing ^{[1
,2
]}

Hu, Chenghong ^{[3
]}

Han, Jibo ^{[4
]}

Luo, Wu ^{[4
]}

Huang, Lijiang ^{[1
]}

Jiang, Yongsheng ^{[1
]}

Samorodov, Aleksandr, V ^{[5
]}

Wang, Yi ^{[1
,3
]}

Huang, Jianxiong ^{[1
]}

机构：

[1] Wenzhou Med Univ, Joint Res Ctr Med, Affiliated Xiangshan Hosp, Ningbo 315700, Peoples R China

[2] Wenzhou Med Univ, Sch & Hosp Stomatol, Inst Stomatol, Wenzhou 325027, Peoples R China

[3] Hangzhou Normal Univ, Sch Pharm, Hangzhou 311121, Peoples R China

[4] Wenzhou Med Univ, Chem Biol Res Ctr, Sch Pharmaceut Sci, Wenzhou 325035, Peoples R China

[5] Bashkir State Med Univ, Dept Pharmacol, Ufa 450005, Russia

来源：

INTERNATIONAL IMMUNOPHARMACOLOGY | 2024年 / 139卷

基金：

俄罗斯科学基金会; 中国国家自然科学基金;

关键词：

Schisandrin B; Ang II; Inflammation; Cardiac inflammatory remodeling; MyD88; TLRs; SIGNALING PATHWAY; HYPERTROPHY; RECOGNITION; PRESSURE; PROTEINS; TRIF;

D O I：

10.1016/j.intimp.2024.112660

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Cardiac tissue remodeling is characterized by altered heart tissue architecture and dysfunction, leading to heart failure. Sustained activation of the renin-angiotensin-aldosterone system (RAAS) greatly promotes the development of myocardial remodeling. Angiotensin II (Ang II), which is the major component of RAAS, can directly lead to cardiac remodeling by inducing an inflammatory response. Schisandrin B (Sch B), the active component extracted from the fruit of Schisandra chinensis (Turcz.) Baill has been shown to exhibit anti-inflammatory activity through its ability to target TLR4 and its adaptor protein, MyD88. In this study, we explored whether Sch B alleviates Ang II-induced myocardial inflammation and remodeling via targeting MyD88. Sch B significantly suppressed Ang II-induced inflammation as well as increased the expression of several genes of tissue remodeling (beta-Mhc, Tgfb, Anp, alpha-Ska) both in vivo and in vitro. These protective effects of Sch B were due to the inhibition of recruitment of MyD88 to TLR2 and TLR4, suppressing the Ang II-induced NF-kappa B activation and reducing the following inflammatory responses. Moreover, the knockdown of Myd88 in cardiomyocytes abrogated the Ang IIinduced increases in the production of inflammatory cytokines and expression of remodeling genes. These findings provide new evidence that the mechanism of Sch B protection was attributed to selective inhibition of MyD88 signaling. This finding could pave the way for novel therapeutic strategies for myocardial inflammatory diseases.

引用

页数：10