Joint Research Center on Medicine, the Affiliated Xiangshan Hospital of Wenzhou Medical University, Ningbo 315700, China; Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou 325027, China.
School of Pharmacy, Hangzhou Normal University, Hangzhou 311121, China.
Int Immunopharmacol. 2024 Sep 30;139:112660. doi: 10.1016/j.intimp.2024.112660. Epub 2024 Jul 16.
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 (β-Mhc, Tgfb, Anp, α-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-κB activation and reducing the following inflammatory responses. Moreover, the knockdown of Myd88 in cardiomyocytes abrogated the Ang II-induced 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.
心肌组织重构的特征是心脏组织结构和功能改变，导致心力衰竭。肾素-血管紧张素-醛固酮系统（RAAS）的持续激活极大地促进了心肌重构的发展。血管紧张素 II（Ang II）是 RAAS 的主要成分，可通过诱导炎症反应直接导致心脏重构。五味子素 B（Sch B）是五味子果实中提取的有效成分，通过靶向 TLR4 和其衔接蛋白 MyD88，显示出抗炎活性。在本研究中，我们探讨了 Sch B 是否通过靶向 MyD88 减轻 Ang II 诱导的心肌炎症和重构。Sch B 显著抑制 Ang II 诱导的炎症以及体内和体外几种组织重构基因（β-Mhc、Tgfb、Anp、α-Ska）的表达增加。Sch B 的这些保护作用归因于抑制 MyD88 向 TLR2 和 TLR4 的募集，抑制 Ang II 诱导的 NF-κB 激活，并减少随后的炎症反应。此外，心肌细胞中 Myd88 的敲低消除了 Ang II 诱导的炎症细胞因子产生和重构基因表达的增加。这些发现为 Sch B 保护的机制归因于选择性抑制 MyD88 信号提供了新的证据。这一发现可能为心肌炎症性疾病的新型治疗策略铺平道路。
