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莱菔硫烷(Maca)多糖通过激活 NRF-2/GPX 和 AhR/STAT3 信号通路减轻黄曲霉毒素 B 的肝毒性。

Lepidium meyenii (Maca) polysaccharides mitigate liver toxicity of aflatoxin B through activation of NRF-2/GPX and AhR/STAT3 signaling pathways.

机构信息

Division of Toxicology, Shandong Center for Disease Control and Prevention, Jinan, 250014, China.

Cheeloo College of Medicine, Shandong University, Jinan, 250012, China.

出版信息

Toxicon. 2024 Nov 6;250:108117. doi: 10.1016/j.toxicon.2024.108117. Epub 2024 Oct 3.

Abstract

Aflatoxin B (AFB) can induce serious liver toxicity in human. While completely avoiding AFB exposure is difficult, dietary intake of natural products may be leveraged to mitigate its adverse health effects. The roots of Lepidium meyenii (Maca) is rich in beneficial polysaccharides. Here we first evaluated dietary safety of MPs and then investigated MPs mitigating effects on the liver toxicity of AFB. A 28-day sub-acute administration of Maca polysaccharides (MPs) demonstrated to be safe in mice at dose 0.2-1.2 g/kg.bw/day that significantly elevated mice stamina. Also, no toxicity was observed in human PC12 cells treated with MPs 25-100 μg/mL which successfully alleviated cobalt-caused cell apoptosis by ∼20%. In terms of anti-AFB hepatoxicity function, MPs 0.4-1.6 g/kg.bw/day significantly alleviated liver tissue damage, lipid accumulation, ROS damage, NF-κB p65, secretion of cytokines such as IL-6 and TNF-α in AFB-treated mice. Flow cytometry found that MPs treatment recovered the elevation of F4/80 in the primary macrophages of AFB-treated mice. At molecular level, MPs treatment activated liver NRF-2/GPX/SOD anti-oxidant system. In human macrophage model, MPs restored the inflammatory AhR/STAT3 pathway and mRNA expressions of Tnf-a, Inos, Arg-1 disrupted by AFB. Our findings not only add to the current understanding on the toxicity mechanism of AFB, but also provide references to the development of dietary intervention strategy using MPs.

摘要

黄曲霉毒素 B(AFB)可导致人类严重的肝毒性。虽然完全避免接触 AFB 较为困难,但可通过饮食摄入天然产物来减轻其对健康的不利影响。玛咖(Lepidium meyenii)的根部富含有益的多糖。本研究首次评估了 MPs 的饮食安全性,然后研究了 MPs 对 AFB 肝毒性的缓解作用。28 天的亚急性 MPs (剂量为 0.2-1.2 g/kg.bw/day)给药在小鼠中表现出安全性,显著提高了小鼠的耐力。此外,在 25-100μg/mL MPs 处理的人 PC12 细胞中未观察到毒性,该浓度可使钴诱导的细胞凋亡减少约 20%。在抗 AFB 肝毒性功能方面,0.4-1.6 g/kg.bw/day 的 MPs 可显著减轻 AFB 处理小鼠的肝组织损伤、脂质积累、ROS 损伤、NF-κB p65 及细胞因子(如 IL-6 和 TNF-α)的分泌。流式细胞术发现,MPs 处理可恢复 AFB 处理小鼠原代巨噬细胞中 F4/80 的升高。在分子水平上,MPs 处理激活了肝脏 NRF-2/GPX/SOD 抗氧化系统。在人巨噬细胞模型中,MPs 恢复了 AFB 破坏的炎症 AhR/STAT3 途径和 Tnf-a、Inos、Arg-1 的 mRNA 表达。本研究结果不仅加深了对 AFB 毒性机制的理解,也为 MPs 作为饮食干预策略的开发提供了参考。

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