姜黄素对β-细胞活力和胰岛素分泌离散毒性的综合研究

IF 3.9 3区医学 Q2 FOOD SCIENCE & TECHNOLOGY

Food and Chemical Toxicology Pub Date : 2025-04-02 DOI:10.1016/j.fct.2025.115429

Rania Derguine , Abdelmalek Rezgui , Rechda Amel Tachour , Imène Zenbout , Rym Agred , Anfel Benmanseur , Fatma-Zahra Hab , Abdelhalim Khenchouche , Widad Sobhi

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引用次数: 0

摘要

姜黄素具有几种治疗作用。然而，这些作用背后的确切机制尚未完全阐明。本研究的目的是强调对β细胞和胰岛的毒性作用。方法研究姜黄素对ALB/c小鼠离体朗格汉胰岛细胞活力和NIT1细胞（NOD小鼠β细胞系CRL-2055™）及胰岛素分泌的毒性作用。我们通过刺激参与UPR反应的三个基因，评估了它对氧化应激标志物、ROS产生的影响，以及它在内质网应激中的作用。在硅和体外研究进行了提取一组基因和姜黄素ppi使用多步骤管道。结果姜黄素能提高朗格汉斯胰岛细胞活力和胰岛素分泌。在60 μg/mL （0,163 μM）浓度下，姜黄素影响β细胞活力，使β细胞活力降低70 - 75%，并显著降低胰岛素分泌。诱导氧化应激，增加NFKB1、ATF4和CHOP的表达。当姜黄素与STZ联合使用时，这些效果得到增强。生物信息学研究表明，姜黄素通过NFkBia与14种蛋白相互作用，包括Jund、Ddit3、Dapk3、Cebpa和NFkB途径。结论姜黄素在高浓度时具有细胞毒性。它诱导与ubr - er和氧化应激相关的β细胞凋亡，涉及NFkB途径及其相关蛋白。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Comprehensive investigation into the discrete toxicity of curcumin on β-cell viability and insulin secretion

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Comprehensive investigation into the discrete toxicity of curcumin on β-cell viability and insulin secretion

Background

Curcumin possesses several therapeutic benefits. However, the precise mechanisms underlying these actions have not been fully elucidated. The aim of this study was to highlight the toxic effects on β-cells and islets.

Methods

The toxic effects of curcumin were investigated on cell viability in ALB/c mouse-isolated Langerhans islets and NIT1 cells (CRL-2055™, a NOD mouse β cell line), and insulin secretion. We evaluated its effects on oxidative stress markers, ROS production, and its role in ER stress through the stimulation of three genes involved in the UPR response. In silico and in vitro studies were conducted to extract a set of genes and curcumin-PPI using a multistep pipeline.

Results

Curcumin increases cell viability and insulin secretion in islets of Langerhans. At 60 μg/mL (0,163 μM), curcumin affected β-cell viability, reducing it by up to 70–75 %, and significantly reduced insulin secretion. It also induces oxidative stress and increases the expression of NFKB1, ATF4, and CHOP. These effects were enhanced when curcumin was combined with STZ. Bioinformatic studies have indicated that curcumin interacts with 14 proteins, including Jund, Ddit3, Dapk3, Cebpa, and the NFkB pathway through NFkBia.

Conclusion

At high concentrations, curcumin is cytotoxic. It induces β-cell apoptosis associated with UPR-ER and oxidative stress, implicating the NFkB pathway and its associated proteins.

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来源期刊

Food and Chemical Toxicology 工程技术-毒理学

CiteScore

10.90

自引率

4.70%

发文量

651

审稿时长

31 days

期刊介绍： Food and Chemical Toxicology (FCT), an internationally renowned journal, that publishes original research articles and reviews on toxic effects, in animals and humans, of natural or synthetic chemicals occurring in the human environment with particular emphasis on food, drugs, and chemicals, including agricultural and industrial safety, and consumer product safety. Areas such as safety evaluation of novel foods and ingredients, biotechnologically-derived products, and nanomaterials are included in the scope of the journal. FCT also encourages submission of papers on inter-relationships between nutrition and toxicology and on in vitro techniques, particularly those fostering the 3 Rs. The principal aim of the journal is to publish high impact, scholarly work and to serve as a multidisciplinary forum for research in toxicology. Papers submitted will be judged on the basis of scientific originality and contribution to the field, quality and subject matter. Studies should address at least one of the following: -Adverse physiological/biochemical, or pathological changes induced by specific defined substances -New techniques for assessing potential toxicity, including molecular biology -Mechanisms underlying toxic phenomena -Toxicological examinations of specific chemicals or consumer products, both those showing adverse effects and those demonstrating safety, that meet current standards of scientific acceptability. Authors must clearly and briefly identify what novel toxic effect (s) or toxic mechanism (s) of the chemical are being reported and what their significance is in the abstract. Furthermore, sufficient doses should be included in order to provide information on NOAEL/LOAEL values.