1. Academic Validation
  2. Buyang Huanwu Decoction suppresses cardiac inflammation and fibrosis in mice after myocardial infarction through inhibition of the TLR4 signalling pathway

Buyang Huanwu Decoction suppresses cardiac inflammation and fibrosis in mice after myocardial infarction through inhibition of the TLR4 signalling pathway

  • J Ethnopharmacol. 2023 Nov 8:117388. doi: 10.1016/j.jep.2023.117388.
Guoyong Zhang 1 Xin Han 1 Tong Xu 1 Min Liu 2 Guanghong Chen 1 Lingpeng Xie 3 Honglin Xu 4 Yue Hua 5 Mingjie Pang 1 Changlei Hu 1 Yuting Wu 6 Bin Liu 7 Yingchun Zhou 8
Affiliations

Affiliations

  • 1 Department of Traditional Chinese Medicine, Nanfang Hospital (ZengCheng Branch), Southern Medical University, Guangzhou, 510515, China; School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, China.
  • 2 Department of Pathogen Biology, School of Public Health, Southern Medical University, Guangzhou, 510515, China.
  • 3 School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, China; Department of Hepatology, Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510315, China.
  • 4 School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, China; Department of geratology, Affliated Dongguan Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan, 523058, China.
  • 5 School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, China.
  • 6 Binzhou Medical University Hospital, Binzhou, 256603, China. Electronic address: 1603406288@qq.com.
  • 7 Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 510260, China. Electronic address: xmhoolv@163.com.
  • 8 Department of Traditional Chinese Medicine, Nanfang Hospital (ZengCheng Branch), Southern Medical University, Guangzhou, 510515, China; School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, China. Electronic address: zhychun@126.com.
Abstract

Ethnopharmacological relevance: It has been reported that cardiac inflammation and fibrosis participate in the development of heart failure (HF) following myocardial infarction (MI). Anti-inflammatory and anti-fibrotic treatments exhibit therapeutic efficacy in MI. Buyang Huanwu Decoction (BYHWD) has cardioprotective properties. However, whether BYHWD regulates cardiac inflammation and fibrosis in HF after MI, and the underlying mechanisms, are still unknown.

Aim of the study: This study aimed to explore the effects and potential mechanisms of BYHWD on cardiac inflammation and fibrosis after MI.

Materials and methods: An MI model was constructed through ligation of the left anterior descending coronary artery (LAD) in mice. The cardioprotective effects of BYHWD were determined by echocardiography, Masson trichrome staining, wheat germ agglutinin (WGA) staining and haematoxylin and eosin (HE) staining. The effects of BYHWD on inflammation and fibrosis, and on the TLR4 signalling pathway, were explored through immunohistochemistry (IHC), Western blot (WB), enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) in vivo. Next, the effects of BYHWD on primary cardiac fibroblasts (CFs) inflammation and collagen synthesis, and on the TLR4 signalling pathway, were detected using WB, immunofluorescence (IF) and qRT-PCR in vitro. In addition, the suppression and overexpression of TLR4 in CFs were further explored.

Results: BYHWD dose-dependently reduced cardiac inflammation, fibrosis and ventricular dysfunction. The expression levels of collagen Ⅰ/Ⅲ, IL-1β and IL-18, as well as critical proteins in the TLR4 signalling pathway and the NLRP3 inflammasome, were suppressed by BYHWD in the in vivo experiment. BYHWD inhibited CFs inflammation and collagen synthesis, as well as critical proteins in the TLR4 signalling pathway and the NLRP3 inflammasome, in the in vitro experiment. TLR4 suppression mitigated these inhibitory effects of BYHWD while overexpression of TLR4 markedly reversed these inhibitory effects of BYHWD.

Conclusion: BYHWD exerts anti-inflammatory and anti-fibrotic effects in mice after MI, and suppresses CFs inflammation and collagen synthesis through suppression of the TLR4 signalling pathway.

Keywords

Buyang huanwu decoction; Heart failure; NF-κB; NLRP3 inflammasome; TLR4.

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