Schisandrol B alleviated diabetic cardiac injury by inhibiting ferroptosis and improving lipid metabolism in mice

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-05-25 DOI:10.1016/j.phymed.2025.156902

Zi-Chang Niu , Qi Jin , Qian-You Shen , Hui-hui Shi , Ye Shang , Xiao-Tong Guo , Meng Wang , Qin Yuan , Hao-Ping Mao

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引用次数: 0

Abstract

Background

Diabetic cardiomyopathy (DCM) is a major complication of diabetes mellitus, highlighting the need to elucidate its pathogenesis and explore potential therapeutic interventions.

Purpose

This study aimed to investigate the cardioprotective mechanisms of SolB in DCM using metabolomic and transcriptomic approaches.

Methods

A DCM mouse model was induced by a high-fat diet combined with streptozotocin (STZ) administration. Cardiac function was assessed, and myocardial structure was examined via echocardiography and HE staining after 10 weeks of SolB treatment. Serum metabolomics and cardiac transcriptomics were performed to identify differentially expressed metabolites and genes, respectively, followed by correlation analysis. Ferroptosis-related proteins were detected by Western blotting (WB). In vitro, H9c2 cells exposed to palmitic acid and high glucose were used to evaluate the effects of SolB on cell viability, ATP production, oxygen consumption, reactive oxygen species (ROS) levels, and mitochondrial membrane potential. Ferroptosis inducer and inhibitor were employed to further explore the underlying mechanisms.

Results

SolB did not significantly alter blood glucose levels but markedly improved cardiac function and myocardial structure. Metabolomic analysis revealed that SolB modulated serum metabolic pathways, including carnitine synthesis and fatty acid oxidation et al. Transcriptomic data indicated that SolB influenced ferroptosis-related pathways. Integrated analysis demonstrated that SolB regulated fatty acid degradation, glutathione metabolism, and cysteine and methionine catabolism. In H9c2 cells, SolB enhanced cell viability, suppressed ferroptosis, reduced lactate dehydrogenase (LDH) release, and improved mitochondrial function.

Conclusions

SolB ameliorates diabetic myocardial injury by inhibiting ferroptosis and improving myocardial lipid metabolism.

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五味子酚B通过抑制铁下垂和改善小鼠脂质代谢减轻糖尿病小鼠心脏损伤

背景：糖尿病性心肌病（DCM）是糖尿病的主要并发症，其发病机制的阐明和治疗干预措施的探索十分必要。目的利用代谢组学和转录组学方法探讨SolB在DCM中的心脏保护机制。方法采用高脂饮食联合链脲佐菌素（STZ）诱导小鼠DCM模型。治疗10周后，通过超声心动图和HE染色检测心功能和心肌结构。血清代谢组学和心脏转录组学分别鉴定差异表达的代谢物和基因，然后进行相关性分析。Western blotting （WB）检测凋亡相关蛋白。在体外，我们利用暴露于棕榈酸和高糖的H9c2细胞来评估SolB对细胞活力、ATP生成、氧气消耗、活性氧（ROS）水平和线粒体膜电位的影响。采用诱导剂和抑制剂进一步探讨其潜在机制。结果solb对血糖无明显影响，但对心功能和心肌结构有明显改善。代谢组学分析显示，SolB调节了血清代谢途径，包括肉碱合成和脂肪酸氧化等。转录组学数据表明，SolB影响铁凋亡相关途径。综合分析表明，SolB调节脂肪酸降解、谷胱甘肽代谢、半胱氨酸和蛋氨酸分解代谢。在H9c2细胞中，SolB提高细胞活力，抑制铁下垂，减少乳酸脱氢酶（LDH）释放，改善线粒体功能。结论solb通过抑制铁下垂和改善心肌脂质代谢改善糖尿病心肌损伤。

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

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.