Inhibition of Mogroside IIIE on isoproterenol-induced myocardial fibrosis through the TLR۴/MyD۸۸/NF-κB signaling pathway

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 C۵۷BL/۶ male mice (۶-۸ weeks) were randomly divided into a control group (n=۱۰), model group (n=۱۰), low MGIIIE dose group (n=۱۰), and high MGIIIE dose group (n=۱۰). Myocardial fibrosis was established by subcutaneous ISO injection. After ۲ 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 ۴ (TLR۴), myeloid differentiation factor ۸۸ (MyD۸۸), p-IκBα, p-NF-κB, transforming growth factor β۱ (TGF-β۱), and α-smooth muscle actin (α-SMA) expression were detected by western blot. Inflammatory cytokines (IL-۱β, IL-۶, and TNF-α) in the serum were examined by ELISA. In the in vitro study, Ang II (۱ μmol/l) was used to stimulate the fibroblasts, then inflammation and fibrosis index were detected.Results: MGIIIE inhibited inflammation and fibrosis and down-regulated TLR۴, MyD۸۸, TGF-β۱, 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 TLR۴/MyD۸۸/NF-κB signaling expression, and decreasing inflammatory cytokine release. MGIIIE may represent a novel therapeutic strategy for treating cardiac fibrosis.

کلیدواژه ها:

Cytokine ، Inflammation ، Myeloid differentiation- factor ۸۸ ، myocardial fibrosis ، NF-κB ، Toll-like receptor ۴