林柏乙醇提取物。绿原酸通过抑制tlr4介导的神经炎症来缓解缺血性脑卒中

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-06-27 DOI:10.1016/j.phymed.2025.157026

Wenze Wu , Libin Xu , Lu Sun , Juan Xue , Feng Wang , Hua Guo , Ning Lei , Dongyao Liu , Yueyang Liu , Dong Liang , Yan Wang , Yan Mi , Huifang Chai , Yue Hou

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引用次数: 0

摘要

背景神经炎症是脑缺血再灌注损伤（CIRI）发病的一个重要因素。林冠病。黑谷藤在中国俗称黑谷藤（HGT），是一种传统的抗炎草药，已被发现对治疗心脑血管疾病有效。然而，其对CIRI的潜在保护作用尚不清楚。目的探讨中药乙醇提取物（EEHGT）对CIRI的药理作用及其机制。方法采用大脑中动脉闭塞-再灌注（MCAO/R）模型和氧-葡萄糖剥夺/再氧合（OGD/R）模型评价EEHGT对大鼠颅脑损伤的保护作用。此外，我们还进行了全面的代谢组学和系统药理学分析，以阐明EEHGT的机制。结果EEHGT能有效减轻MCAO/R大鼠的CIRI，减轻OGD/R处理的SH-SY5Y细胞的神经元损伤。值得注意的是，EEHGT减轻了促炎细胞因子的分泌，并恢复了关键炎症相关代谢物的水平，包括精氨酸、乳酸和l -酪氨酸。网络药理学分析表明，PI3K-Akt和NF-κB信号通路参与介导EEHGT的神经保护和抗炎活性。与此结果一致，EEHGT在MCAO/R大鼠和OGD/R处理的BV2细胞中激活了PI3K-Akt通路，抑制了NF-κB信号传导。结果表明，TLR4是EEHGT在CIRI中的关键介质，TLR4敲除可消除其抗神经炎症作用。此外，EEHGT的活性化合物绿原酸（chlorogenic acid， CGA）与TLR4具有较强的结合亲和力，其抗炎活性在TLR4敲低后被消除。总之，本研究提供了EEHGT通过减弱tlr4介导的神经炎症来预防CIRI的第一个证据。机制上，EEHGT通过激活PI3K-Akt通路，抑制NF-κB信号通路发挥抗炎作用。值得注意的是，TLR4被确定为EEHGT及其活性成分CGA的共同治疗靶点，强调了其神经保护作用的新机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Ethanol extract of Periploca forrestii Schltr. and chlorogenic acid alleviate ischemic stroke by inhibiting TLR4-mediated neuroinflammation

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Ethanol extract of Periploca forrestii Schltr. and chlorogenic acid alleviate ischemic stroke by inhibiting TLR4-mediated neuroinflammation

Background

Neuroinflammation is a major factor in the pathogenesis of cerebral ischemia-reperfusion injury (CIRI). Periploca forrestii Schltr., commonly known as Heiguteng (HGT) in China, is a traditional anti-inflammatory herb that has been found effective in treating cardiovascular and cerebrovascular diseases. However, its potential protective effects against CIRI remain unclear.

Purpose

This study aimed to investigate the pharmacological actions and underlying mechanisms of ethanol extract of HGT (EEHGT) on CIRI.

Methods

The middle cerebral artery occlusion-reperfusion (MCAO/R) and oxygen-glucose deprivation/reoxygenation (OGD/R) models were used to evaluate the protective effects of EEHGT on CIRI. Additionally, comprehensive metabolomics and systems pharmacology analyses were performed to elucidate the mechanisms of EEHGT.

Results

The results demonstrated that EEHGT effectively alleviated CIRI in MCAO/R rats and reduced neuronal damage in OGD/R-treated SH-SY5Y cells. Notably, EEHGT mitigated the secretion of pro-inflammatory cytokines and restored the levels of key inflammation-related metabolites, including arginine, lactate, and L-tyrosine. Network pharmacology analysis indicated that the PI3K-Akt and NF-κB signaling pathways are involved in mediating the neuroprotective and anti-inflammatory activities of EEHGT. Consistent with this result, EEHGT activated PI3K-Akt pathway and inhibited NF-κB signaling in both MCAO/R rats and OGD/R-treated BV2 cells. The results indicated that TLR4 serves as a key mediator of EEHGT on CIRI, and TLR4 knockdown abolished its anti-neuroinflammatory effects. In addition, chlorogenic acid (CGA), an active compound of EEHGT, exhibited strong binding affinity to TLR4, and its anti-inflammatory activity was abolished upon TLR4 knockdown.

Conclusions

Collectively, this study provides the first evidence that EEHGT protects against CIRI by attenuating TLR4-mediated neuroinflammation. Mechanistically, EEHGT exerts its anti-inflammatory effects by activating the PI3K-Akt pathway and inhibiting NF-κB signaling. Notably, TLR4 was identified as a shared therapeutic target of both EEHGT and its active component, CGA, highlighting a novel mechanism underlying their neuroprotective effects.

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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.