Acacetin ameliorates pressure overload-induced cardiac remodeling by targeting USP10 and inhibiting maladaptive cardiomyocyte autophagy

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-03-05 DOI:10.1016/j.phymed.2025.156588

Gaoyuan Ge , Wei Zhao , Zhuen Zhong , Youfu Huang , Yan Hua , Kaiyan Chen , Yue Yu , Tianyu Wu , Yao Lu , Nishant Yadav , Fengxiang Zhang

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Abstract

Background

Numerous drugs have been developed to meet the critical demand for treatments inhibiting cardiac remodeling following cardiovascular disease. Acacetin is a flavonoid with potential therapeutic effects against various cardiovascular diseases. Purpose: This study investigated the effect of acacetin on pressure overload-induced cardiac remodeling and its underlying molecular regulatory mechanisms.

Methods

We simulated pressure overload-induced cardiac remodeling in male C57BL/6 mice by constricting the thoracic aortic arch and assessed the effect of acacetin on cardiac remodeling.

Results

Acacetin significantly ameliorated cardiac remodeling by downregulating ubiquitin-specific peptidase 10 (USP10) protein expression and reducing autophagy levels in cardiomyocytes. These findings confirm that acacetin improves cardiac remodeling by suppressing cardiomyocyte autophagy and highlight the crucial role of USP10 in the Beclin 1 ubiquitination degradation-mediated inhibition of the cardiomyocyte autophagy signaling pathway.

Conclusion

These results suggest that acacetin is a promising candidate drug for the treatment of cardiac remodeling induced by pressure overload.

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来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.