Inhibition of Mogroside IIIE on isoproterenol-induced myocardial fibrosis through the TLR4/MyD88/NF-κB signaling pathway

Document Type : Original Article

Authors

1 Department of Cardiology, the Fourth Affiliated Hospital, Harbin Medical University, Harbin, PR. China, 150001

2 Department of Cardiology, the Harbin Medical University, Harbin, PR. China, 150001

3 Heilongjiang Provincial Hospital, Harbin, PR. China, 150001

4 Department of Geriatric Cardiology, Guangdong Provincial People’s Hospital. Guangzhou, PR. China, 510080

Abstract

Objective(s): To investigate the effect of mogroside IIIE (MGIIIE) on isoproterenol (ISO)-induced myocardial fibrosis and explore its possible mechanisms.
Materials and Methods: Forty C57BL/6 male mice (6-8 weeks) were randomly divided into a control group (n=10), model group (n=10), low MGIIIE dose group (n=10), and high MGIIIE dose group (n=10). Myocardial fibrosis was established by subcutaneous ISO injection. After 2 weeks of continuous gastric administration of MGIIIE, the cardiac structure was evaluated by echocardiography. Myocardial inflammation and fibrosis were evaluated by histology examination. Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), p-IκBα, p-NF-κB, transforming growth factor β1 (TGF-β1), and α-smooth muscle actin (α-SMA) expression were detected by western blot. Inflammatory cytokines (IL-1β, IL-6, and TNF-α) in the serum were examined by ELISA. In the in vitro study, Ang II (1 μmol/l) was used to stimulate the fibroblasts, then inflammation and fibrosis index were detected.
Results: MGIIIE inhibited inflammation and fibrosis and down-regulated TLR4, MyD88, TGF-β1, and α-SMA expression in the myocardium. In the in vitro study, MGIIIE ameliorates the deposition of Col Ш and Col I and decreases the release of inflammatory cytokines. MGIIIE increased p-IκBα and reduced p-NF-κB expression both in vivo and in vitro.
Conclusion: MGIIIE plays a role in anti-myocardial fibrosis, by inhibiting TLR4/MyD88/NF-κB signaling expression, and decreasing inflammatory cytokine release. MGIIIE may represent a novel therapeutic strategy for treating cardiac fibrosis.

Keywords

References

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Iranian Journal of Basic Medical Sciences
Volume 26, Issue 1
January 2023
Pages 114-120

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