Bisdemethoxycurcumin attenuates myocardial fibrosis in heart failure with preserved ejection fraction by targeting TGFBR1 and oxidative stress

TL;DR

Bisdemethoxycurcumin reduces heart scarring in a type of heart failure by targeting a key protein and reducing stress in the heart.

Contribution

This study identifies Bisdemethoxycurcumin as a novel compound that targets TGFBR1 to reduce myocardial fibrosis in HFpEF.

Findings

BDMC treatment improved cardiac function and reduced fibrosis in a HFpEF mouse model.

BDMC competitively inhibits TGF-β binding to TGFBR1, suppressing fibroblast activation.

Molecular simulations confirmed stable interaction between BDMC and TGFBR1.

Abstract

Bisdemethoxycurcumin (BDMC), a natural derivative of curcumin with improved solubility and stability, has shown potential cardioprotective properties. This study investigated the efficacy and underlying mechanisms of BDMC in heart failure with preserved ejection fraction (HFpEF) using both in vivo and in vitro models. The HFpEF mouse model was established using a high-fat diet and L-NAME. BDMC treatment improved cardiac function, attenuated myocardial fibrosis, and exhibited antioxidant effects. Mechanistically, integrated network pharmacology and proteomics identified TGFBR1 as a potential target. BDMC inhibited cardiac fibroblast activation by suppressing TGFBR1 expression and SMAD2/3 phosphorylation. Molecular docking and dynamics simulations confirmed stable binding between BDMC and TGFBR1. These findings demonstrate that BDMC mitigates myocardial fibrosis in HFpEF, primarily by competitively inhibiting the binding of TGF-β and TGFBR1, achieving the effect of inhibiting cardiac fibroblast activation.

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