番茄红素通过肠-脑轴改善邻苯二甲酸二（2-乙基己基）诱导的小鼠神经毒性

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-07-05 DOI:10.1016/j.phymed.2025.157057

Li-Jian Chen , Yi Liu , Jia-Li Liu , Zhi-Jiang Chen , Wei Zhao , Ji-Hui Li , Clare Hsu , Long Chen , Jia-Hao Zeng , Xiu-Wen Li , Jian-Zheng Yang , Jia-Hao Li , Xiao-Li Xie , Shao-Hua Tao , Qi Wang

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引用次数: 0

摘要

邻苯二甲酸二（2-乙基己基）酯（DEHP）是一种普遍存在于许多消费品中的增塑剂，通过环境和饮食暴露会造成严重的神经毒性风险。越来越多的证据强调了dehp诱导的神经毒性和肠道微生物群失调之间的关键关联。天然类胡萝卜素番茄红素（Lyc）以其强大的抗氧化和抗炎能力而闻名，在治疗各种神经系统疾病方面显示出治疗前景。目的探讨Lyc对dehp诱导的小鼠神经毒性的潜在神经保护机制，重点研究其与肠-脑轴的相互作用。方法小鼠连续35 d，每天灌胃DEHP或Lyc。采用综合转录组、微生物组和分子生物学分析的综合方法，结合细菌治疗，彻底研究了潜在的机制。结果我们的研究结果表明，Lyc给药或Lyc处理小鼠的粪便微生物群移植（FMT）可有效改善dehp诱导的焦虑和抑郁样行为。在分子水平上，Lyc可能通过调节nod样受体信号通路减轻海马神经炎症。此外，Lyc处理通过促进有益菌（如Akkermansiaceae）的生长来改善肠道菌群组成，并通过增加紧密连接蛋白的表达来增强肠道屏障的完整性。Lyc还调节结肠中的LPS-TLR4/MyD88信号通路，从而减轻局部炎症。结论：这些结果提供了令人信服的证据，表明Lyc通过调节肠-脑轴、抑制神经炎症和恢复肠道稳态等多方面的策略，对dehp诱导的神经毒性具有保护作用。我们提出了一种新的治疗策略来减轻DEHP对神经和肠道健康造成的风险。这种方法包括补充Lyc或应用细菌疗法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Lycopene ameliorates Di-(2-ethylhexyl) phthalate-induced neurotoxicity in mice via the gut-brain axis

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Lycopene ameliorates Di-(2-ethylhexyl) phthalate-induced neurotoxicity in mice via the gut-brain axis

Background

Di(2-ethylhexyl) phthalate (DEHP), a ubiquitous plasticizer present in numerous consumer products, poses a substantial neurotoxic risk through environmental and dietary exposure. Growing evidence highlights a critical association between DEHP-induced neurotoxicity and gut microbiota dysbiosis. Renowned for its potent antioxidant and anti-inflammatory capabilities, the natural carotenoid lycopene (Lyc) demonstrates therapeutic promise in treating various neurological disorders.

Purpose

The potential neuroprotective mechanisms of Lyc against DEHP-induced neurotoxicity in mice were investigated in this study, with a specific focus on its interaction with the gut-brain axis.

Methods

For 35 consecutive days, mice received daily intragastric administrations of DEHP or Lyc. A comprehensive approach involving integrated transcriptome, microbiome, and molecular biology analyses, in conjunction with bacteriotherapy, was utilized to thoroughly investigate the underlying mechanisms.

Results

Our findings demonstrated that Lyc administration or fecal microbiota transplantation (FMT) from Lyc-treated mice effectively ameliorated DEHP-induced anxiety- and depression-like behaviors. At the molecular level, Lyc mitigated neuroinflammation in the hippocampus, potentially through modulation of the NOD-like receptor signaling pathway. Furthermore, Lyc treatment improved gut microbiota composition by promoting the growth of beneficial bacteria, such as Akkermansiaceae, and enhanced intestinal barrier integrity via increased expression of tight junction proteins. Lyc also regulated the LPS-TLR4/MyD88 signaling pathway in the colon, thereby reducing local inflammation.

Conclusion

These results provide compelling evidence that Lyc confers protection against DEHP-induced neurotoxicity through a multifaceted strategy involving modulation of gut-brain axis, suppression of neuroinflammation, and restoration of gut homeostasis. We propose a novel therapeutic strategy to alleviate the risks posed by DEHP to both neurological and intestinal health. This approach involves either supplementation with Lyc or the application of bacteriotherapy.

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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.