Lignans of Schisandra chinensis (Turcz.) Baill inhibits Parkinson's disease progression through mediated neuroinflammation-TRPV1 expression in microglia

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL Phytomedicine Pub Date : 2024-10-11 DOI:10.1016/j.phymed.2024.156146

Si-Yi Wang , Meng-Meng Li , Jia-Tong Wu , Ye Sun , Juan Pan , Wei Guan , Anam Naseem , Adnan Mohammed Algradi , Hai-Xue Kuang , Yi-Kai Jiang , Hong-Yan Yao , Xiao-Xue He , Hua Li , Bing-You Yang , Yan Liu

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Abstract

Background

Schisandra chinensis (Turcz.) Baill (S. chinensis), a member of the Magnoliaceae family, is renowned for its distinctive medicinal attributes and is commonly employed in the treatment of disorders affecting the CNS.

Purpose

The potential therapeutic effects of a lignan-enriched extract derived from Schisandra chinensis (Turcz.) Baill (LSC) on PD is assessed, which focuses on its mechanisms of action in addressing neuroinflammation.

Methods

The LSC has been obtained by purifying the ethyl alcohol extract of S. chinensis. The Orbitrap-MS method has been employed to analyze the chemical composition of the LSC. In LPS-induced BV2 cells, LSC-induced changes in M1/M2 type inflammatory cytokines have been examined using the Griess reaction, Elisa, JC-1, flow cytometry, IF, and WB methods. A model of PD has been established by treatment of MPTP in C57BL/6 mice. The effect of LSC on behavioral changes, inflammatory factor levels, expression of TH and IBA-1, and production of autophagy in the midbrain has been investigated by TEM, immunohistochemistry, Elisa, and WB.

Results

LSC has relieved sports injuries and pathological damage, and targeted the TRPV1-AMPK-NLRP3 signaling pathway, which affected neuroinflammation and autophagy in vivo. Furthermore, in vitro investigations demonstrated that LSC has activated M1/M2 transformation, its related inflammatory factors, and protein expressions of the NLRP3-Caspase1 signaling pathway in LPS-BV2 cells. The research notably demonstrated that the LSC promoted autophagy and suppressed inflammation through targeting TRPV1.

Conclusion

In the investigation, LSC focused on TRPV1 and controlled neuroinflammation-autophagy by regulating AMPK-NLRP3, which has been proven for the first time. The study has presented molecular data supporting the use of LSC in treating PD and offers references for developing drugs. Remarkably, LSC has the potential to be utilized as a therapeutic or health medication that could significantly decrease PD.

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五味子木脂素通过介导小胶质细胞中的神经炎症-TRPV1表达抑制帕金森病的进展。

背景：目的：本研究评估了五味子（Turcz：方法：通过纯化五味子乙醇提取物获得 LSC。采用 Orbitrap-MS 方法分析 LSC 的化学成分。在 LPS 诱导的 BV2 细胞中，使用 Griess 反应、Elisa、JC-1、流式细胞术、IF 和 WB 方法检测了 LSC 诱导的 M1/M2 型炎症细胞因子的变化。通过对 C57BL/6 小鼠进行 MPTP 治疗，建立了帕金森病模型。通过TEM、免疫组化、Elisa和WB等方法研究了LSC对中脑行为变化、炎症因子水平、TH和IBA-1的表达以及自噬产生的影响：结果：LSC能缓解运动损伤和病理损伤，靶向TRPV1-AMPK-NLRP3信号通路，影响体内神经炎症和自噬。此外，体外研究表明，LSC 能激活 LPS-BV2 细胞中的 M1/M2 转化及其相关炎症因子和 NLRP3-Caspase1 信号通路的蛋白表达。研究显著表明，LSC 通过靶向 TRPV1 促进自噬和抑制炎症：在研究中，LSC 聚焦于 TRPV1，通过调节 AMPK-NLRP3 控制神经炎症-自噬，这是首次得到证实。该研究提出了支持使用 LSC 治疗帕金森病的分子数据，并为开发药物提供了参考。值得注意的是，LSC 具有作为治疗或保健药物的潜力，可显著减轻帕金森病。

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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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.