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通过 AMPK-mTOR 和 PPARγ-NF-κB 信号通路对葛根素降血糖活性的代谢组学分析。

Metabolomic analysis of the Puerarin hypoglycemic activity via AMPK-mTOR and PPARγ-NF-κB signaling pathways.

机构信息

School of Food science and Engineering, Shaanxi University of Science and Technology, Xi' an 710021, China; School of Biological and Pharmaceutical Sciences, Shaanxi University of Science and Technology, Xi' an 710021, China.

School of Food science and Engineering, Shaanxi University of Science and Technology, Xi' an 710021, China; School of Biological and Pharmaceutical Sciences, Shaanxi University of Science and Technology, Xi' an 710021, China.

出版信息

Phytomedicine. 2024 Jul 25;130:155546. doi: 10.1016/j.phymed.2024.155546. Epub 2024 Apr 2.

DOI:10.1016/j.phymed.2024.155546
PMID:38833790
Abstract

BACKGROUND

Diabetes mellitus (DM) is a chronic metabolic disease characterized by hyperglycemia, and its increasing prevalence is a global concern. Early diagnostic markers and therapeutic targets are essential for DM prevention and treatment. Pueraria, derived from kudzu root, is used clinically for various symptoms, and its active compound, Puerarin, shows promise in improving insulin resistance and reducing inflammation.

PURPOSE

This study aims to evaluate the protective effects of metformin and Puerarin at different doses in an STZ-induced DM mouse model. The intricate metabolites within the serum of STZ-induced diabetic mice were subjected to thorough investigation, thus elucidating the intricate mechanism through which Puerarin demonstrates notable efficacy in the treatment of diabetes.

METHODS

An STZ-induced DM mouse model is established. Mice are treated with metformin and puerarin at varying doses. Physiological, biochemical, and histomorphological assessments are performed. Metabolomics analysis is carried out on serum samples from control, DM, metformin, and medium-dose Puerarin groups. Western blot and qRT-PCR technologies are used to validate the mechanisms.

RESULTS

The DM mouse model replicates abnormal blood glucose, insulin levels, physiological, biochemical irregularities, as well as liver and pancreas damage. Treatment with metformin and Puerarin restores these abnormalities, reduces organ injury, and modulates AMPK, PPARγ, mTOR, and NF-κB protein and mRNA expression. Puerarin activates the AMPK-mTOR and PPARγ-NF-κB signaling pathways, regulating insulin signaling, glucolipid metabolism, and mitigating inflammatory damage.

CONCLUSION

This study demonstrates that Puerarin has the potential to treat diabetes by modulating key signaling pathways. The focus was on the finding that Puerarin has been shown to improve insulin signaling, glucolipid metabolism and attenuate inflammatory damage through the modulation of the AMPK-mTOR and PPARγ-NF-κB pathways. The discovery of Puerarin's favorable protective effect and extremely complex mechanism highlights its prospect in the treatment of diabetes and provides theoretical support for its comprehensive development and utilization.

摘要

背景

糖尿病(DM)是一种以高血糖为特征的慢性代谢性疾病,其发病率的增加是一个全球性的关注点。早期诊断标志物和治疗靶点对于糖尿病的预防和治疗至关重要。葛根来源于野葛,临床上用于治疗各种症状,其活性化合物葛根素在改善胰岛素抵抗和减轻炎症方面显示出潜力。

目的

本研究旨在评估不同剂量二甲双胍和葛根素在 STZ 诱导的糖尿病小鼠模型中的保护作用。深入研究 STZ 诱导的糖尿病小鼠血清中的复杂代谢物,阐明葛根素在治疗糖尿病方面具有显著疗效的复杂机制。

方法

建立 STZ 诱导的糖尿病小鼠模型。用不同剂量的二甲双胍和葛根素处理小鼠。进行生理、生化和组织形态学评估。对对照组、糖尿病组、二甲双胍组和中剂量葛根素组的血清样本进行代谢组学分析。采用 Western blot 和 qRT-PCR 技术验证机制。

结果

糖尿病小鼠模型复制了异常的血糖、胰岛素水平、生理、生化异常以及肝和胰腺损伤。用二甲双胍和葛根素治疗可恢复这些异常,减轻器官损伤,并调节 AMPK、PPARγ、mTOR 和 NF-κB 蛋白和 mRNA 表达。葛根素激活 AMPK-mTOR 和 PPARγ-NF-κB 信号通路,调节胰岛素信号、糖脂代谢,并减轻炎症损伤。

结论

本研究表明,葛根素通过调节关键信号通路具有治疗糖尿病的潜力。研究重点是发现葛根素通过调节 AMPK-mTOR 和 PPARγ-NF-κB 通路,改善胰岛素信号、糖脂代谢和减轻炎症损伤。葛根素的有利保护作用和极其复杂的机制的发现突出了其在糖尿病治疗中的前景,为其全面开发利用提供了理论支持。

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