Timosaponin AIII alleviates type 2 diabetes-induced cardiomyopathy by targeting galectin-3 (LGALS3)

IF 3.5 3区生物学 Q3 CELL BIOLOGY

Experimental cell research Pub Date : 2025-06-30 DOI:10.1016/j.yexcr.2025.114665

Jing Yin , Chenxi Yu , Zhongyong Zhang , Jialin Cong

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引用次数: 0

Abstract

Timosaponin AIII, the main active saponin derived from Anemarrhena asphodeloides Bunge, exerts anti-diabetic effects. However, its underlying mechanism in diabetic cardiomyopathy (DCM) remains unclear. In this study, we explored the pharmacological effects of timosaponin AIII on DCM using a mouse model and H9c2 cells. We found that timosaponin AIII treatment attenuated cardiac remodeling, myocardial fibrosis, and cardiomyocyte apoptosis in high-fat diet (HFD) combined with streptozotocin (STZ)-induced diabetic mice. Additionally, it significantly reduced galectin-3 expression in HFD/STZ-induced heart tissue and HG-exposed H9c2 cells. Mechanistically, timosaponin AIII facilitated the ubiquitin-dependent degradation of galectin-3. Notably, in timosaponin AIII-treated H9c2 cells, overexpression of galectin-3 significantly restored cardiomyocyte apoptosis and oxidative stress. Taken together, our data confirmed that timosaponin AIII demonstrated cardioprotective effects in diabetic mice by reducing fibrosis and apoptosis. These findings suggest a promising pharmacological strategy for treating DCM.

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Timosaponin AIII通过靶向半凝集素-3 （LGALS3）缓解2型糖尿病诱导的心肌病

苦参皂苷AIII是苦参的主要活性皂苷，具有抗糖尿病作用。然而，其在糖尿病性心肌病（DCM）中的潜在机制尚不清楚。在本研究中，我们通过小鼠模型和H9c2细胞，探讨了timamoaponin AIII对DCM的药理作用。我们发现，在高脂肪饮食（HFD）联合链脲佐菌素（STZ）诱导的糖尿病小鼠中，肽腺苷AIII治疗可减轻心脏重构、心肌纤维化和心肌细胞凋亡。此外，它显著降低了HFD/ stz诱导的心脏组织和hg暴露的H9c2细胞中半凝集素-3的表达。从机制上讲，timosaponin AIII促进了泛素依赖性半乳糖凝集素-3的降解。值得注意的是，在timosaponin aiii处理的H9c2细胞中，过表达半乳糖凝集素-3可显著恢复心肌细胞凋亡和氧化应激。综上所述，我们的数据证实，timosaponin AIII通过减少纤维化和细胞凋亡在糖尿病小鼠中表现出心脏保护作用。这些发现提示了一种治疗DCM的有希望的药理学策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Experimental cell research 医学-细胞生物学

CiteScore

7.20

自引率

0.00%

发文量

295

审稿时长

30 days

期刊介绍： Our scope includes but is not limited to areas such as: Chromosome biology; Chromatin and epigenetics; DNA repair; Gene regulation; Nuclear import-export; RNA processing; Non-coding RNAs; Organelle biology; The cytoskeleton; Intracellular trafficking; Cell-cell and cell-matrix interactions; Cell motility and migration; Cell proliferation; Cellular differentiation; Signal transduction; Programmed cell death.