Herpotrichone A Exerts Neuroprotective Effects by Relieving Ferroptosis,Journal of Agricultural and Food Chemistry

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Herpotrichone A Exerts Neuroprotective Effects by Relieving Ferroptosis
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2024-07-23 , DOI: 10.1021/acs.jafc.4c02418
Jia-Le Deng ₁ , Guo-Yan Wang ₂ , Yi-Jie Zhai ₁ , Xu-Yao Feng ₁ , Lu Deng ₂ , Wen-Bo Han ₁ , Jiang-Jiang Tang _{1,

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Affiliation

Inhibition of oxidative stress and ferroptosis is currently considered to be a promising therapeutic approach for neurodegenerative diseases. Herpotrichones, a class of compounds derived from insect symbionts, have shown potential for neuroprotective activity with low toxicity. However, the specific mechanisms through which herpotrichones exert their neuroprotective effects remain to be fully elucidated. In this study, the natural [4 + 2] adducts herpotrichone A (He-A) and its new analogues were isolated from the isopod-associated fungus Herpotrichia sp. SF09 and exhibited significantly protective effects in H₂O₂-, 6-OHDA-, and RSL3-stimulated PC12 cells and LPS-stimulated BV-2 cells. Moreover, He-A was able to relieve ferroptotic cell death in RSL3-stimulated PC12 cells and 6-OHDA-induced zebrafish larvae. Interestingly, He-A can activate antioxidant elements and modulate the SLC7A11 pathway without capturing oxidic free radical and chelating iron. These findings highlight He-A as a novel hit that protects against ferroptosis-like neuronal damage in the treatment of neurodegenerative diseases.

中文翻译：

Herpotrichone A 通过缓解铁死亡发挥神经保护作用

抑制氧化应激和铁死亡目前被认为是神经退行性疾病的一种有前途的治疗方法。 Herpotrichones 是一类源自昆虫共生体的化合物，已显示出低毒性的神经保护活性潜力。然而，两栖动物发挥神经保护作用的具体机制仍有待充分阐明。在本研究中，从等足类真菌Herpotrichia sp. 中分离出天然 [4 + 2] 加合物 Herpotrichone A ( He-A ) 及其新类似物。 SF09对H ₂ O ₂ -、6-OHDA-和RSL3刺激的PC12细胞和LPS刺激的BV-2细胞表现出显着的保护作用。此外， He-A能够减轻 RSL3 刺激的 PC12 细胞和 6-OHDA 诱导的斑马鱼幼虫的铁死亡。有趣的是， He-A可以激活抗氧化元素并调节 SLC7A11 通路，而不捕获氧化自由基和螯合铁。这些发现凸显了He-A是一种新的热门药物，可以在神经退行性疾病的治疗中防止铁死亡样神经元损伤。

更新日期：2024-07-23

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