Linggui Zhugan decoction delays ventricular remodeling in rats with chronic heart failure after myocardial infarction through the Wnt/β-catenin signaling pathway

Mingming Yang; Haiyan Wu; Hang Qian; Dongfeng Li; Hao Xu; Jishun Chen; Jixin Zhong; Wenwen Wu; Handong Yang; Xinlong Chen; Xinwen Min; Jun Chen

doi:10.1016/j.phymed.2023.155026

Linggui Zhugan decoction delays ventricular remodeling in rats with chronic heart failure after myocardial infarction through the Wnt/β-catenin signaling pathway

Phytomedicine. 2023 Nov:120:155026. doi: 10.1016/j.phymed.2023.155026. Epub 2023 Aug 16.

Authors

Mingming Yang¹, Haiyan Wu¹, Hang Qian¹, Dongfeng Li¹, Hao Xu¹, Jishun Chen¹, Jixin Zhong², Wenwen Wu³, Handong Yang¹, Xinlong Chen⁴, Xinwen Min⁵, Jun Chen⁶

Affiliations

¹ Sinopharm Dongfeng General Hospital (Hubei Clinical Research Center of Hypertension), Hubei University of Medicine, Hubei Key Laboratory of Wudang Local Chinese Medicine Research (Hubei University of Medicine), Shiyan, China.
² Department of Rheumatology and Immunology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
³ School of Public Health, Hubei University of Medicine, Shiyan, Hubei, China.
⁴ Yunxi Hospital of Chinese Medicine, Shiyan, Hubei 442600, China. Electronic address: 13886801380@163.com.
⁵ Sinopharm Dongfeng General Hospital (Hubei Clinical Research Center of Hypertension), Hubei University of Medicine, Hubei Key Laboratory of Wudang Local Chinese Medicine Research (Hubei University of Medicine), Shiyan, China. Electronic address: minxinwen@163.com.
⁶ Sinopharm Dongfeng General Hospital (Hubei Clinical Research Center of Hypertension), Hubei University of Medicine, Hubei Key Laboratory of Wudang Local Chinese Medicine Research (Hubei University of Medicine), Shiyan, China. Electronic address: chenjun0121@126.com.

PMID: 37619320
DOI: 10.1016/j.phymed.2023.155026

Abstract

Context: Traditional Chinese medicine plays an important role in the prevention and treatment of heart failure (HF). Linggui Zhugan decoction has been approved for clinical treatment of chronic HF. However, the mechanism is still unclear.

Objective: The effect of Linggui Zhugan decoction on the Wnt/β-catenin signaling pathway in rat myocardium was studied to investigate the mechanism by Linggui Zhugan decoction effects ventricular remodeling in rats with heart failure after myocardial infarction.

Method: A rat model of HF after myocardial infarction was prepared by ligating the left anterior descending coronary artery. After 6 weeks of intervention with Linggui Zhugan decoction, the effect of Linggui Zhugan decoction on the cardiac function of chronic HF model rats was observed. Myocardial infarct size was measured by triphenyl tetrazolium chloride (TTC) staining. Enzyme linked immunosorbent assays (ELISAs) were used to measure NT-proBNP and sST-2 concentrations in rat serum. Hematoxylin and eosin (H&E) staining, and Masson's trichrome staining were used to observe the morphology of myocardial tissue; immunohistochemistry was used to detect the protein expression of type I collagen and type III collagen in myocardial tissue; and mRNA expression levels of Wnt3a, GSK-3β, β-catenin, and c-Myc in the infarct marginal zone were detected using PCR. Protein expression of Wnt3a, p-GSK-3β, GSK-3β, and β-catenin in the infarct marginal zone was detected using western blot.

Results: Compared with the control, Linggui Zhugan decoction reduced the levels of serum ST-2 and NT-proBNP, improved cardiac function, and reduced the deposition of collagen fiber. In addition, Linggui Zhugan decoction inhibited the expression of Wnt3a, p-GSK-3β, and β-catenin in cardiomyocytes.

Conclusion: Linggui Zhugan decoction inhibits the expression of several key proteins in the Wnt/β-catenin signaling pathway, delays cardiomyocyte hypertrophy and fibrosis, and improves cardiac function.

Keywords: Animal experiments; Heart failure; Myocardial infarction; Traditional Chinese Medicine; Ventricular remodeling.

MeSH terms

Animals
Glycogen Synthase Kinase 3 beta / metabolism
Heart Failure* / metabolism
Myocardial Infarction* / drug therapy
Rats
Ventricular Remodeling
Wnt Signaling Pathway
beta Catenin / metabolism

Substances

beta Catenin
Glycogen Synthase Kinase 3 beta