L-NRB alleviates amyotrophic lateral sclerosis by regulating P11-Htr4 signaling pathway.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Pub Date : 2024-11-01 Epub Date: 2024-10-19 DOI:10.1016/j.biopha.2024.117588

Yunfeng Pan, Xiao Sun, Yu Tian, Miao Yu, Yun Luo, Xiaobo Sun

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Abstract

Introduction: L-NRB is a compound formed as a ring cleavage product of butylphthalide and borneol in a molar ratio 1:2. This study aimed to explore the therapeutic effect of L-NRB on amyotrophic lateral sclerosis (ALS) and its possible mechanism.

Methods: SOD1-G93A mice were used as an ALS model. Behavioral tests, histopathological staining, Nissl staining, immunohistochemistry, enzyme-linked immunosorbent assays, and Western blotting were used to analyze the therapeutic effect. The underlying mechanism of L-NRB in treating ALS was investigated using transcriptomic analyses.

Results: It was found that L-NRB alleviated motor dysfunction, pathological changes in the gastrocnemius muscle, and motor neuron injuries. The results indicated that L-NRB had a neuroprotective function associated with the inhibition of neuroinflammation. The anti-apoptotic effect of L-NRB was found to be related to the regulation of the P11-Htr4 signaling pathway.

Conclusion: In summary, the results demonstrated the therapeutic effect of L-NRB on ALS and suggest a promising new therapeutic candidate for ALS.

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L-NRB通过调节P11-Htr4信号通路缓解肌萎缩性脊髓侧索硬化症。

简介L-NRB是丁基酞和硼酮醇以1:2的摩尔比裂环生成的化合物。本研究旨在探讨 L-NRB 对肌萎缩性脊髓侧索硬化症（ALS）的治疗效果及其可能的机制：方法：采用 SOD1-G93A 小鼠作为 ALS 模型。方法：以 SOD1-G93A 小鼠为 ALS 模型，通过行为测试、组织病理学染色、Nissl 染色、免疫组织化学、酶联免疫吸附试验和 Western 印迹分析其治疗效果。通过转录组分析研究了L-NRB治疗ALS的内在机制：结果发现，L-NRB能缓解运动功能障碍、腓肠肌病理变化和运动神经元损伤。结果表明，L-NRB 具有与抑制神经炎症相关的神经保护功能。结论：L-NRB 的抗凋亡作用与 P11-Htr4 信号通路的调节有关：总之，研究结果表明了 L-NRB 对 ALS 的治疗作用，并提出了一种治疗 ALS 的新候选药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

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