Yangyin Yiqi Huoxue Decoction improves the mechanism of microglia activation against CIS-induced neuroinflammatory injury by regulating the Wnt signaling pathway

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-01-12 DOI:10.1016/j.phymed.2025.156387

Ting Lu , Ying Huang , Jiehong Yang , Chongyu Shao , Haitong Wan

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引用次数: 0

Abstract

Background

Ischemic stroke is a predominant cause of neurological disability, characterized by neuroinflammation and neuronal apoptosis. The Wnt signaling pathway plays a critical role in brain repair. Yangyin Yiqi Huoxue Decoction, a traditional Chinese herbal formula, has shown potential in alleviating neuroinflammatory injury, yet, the precise mechanism underlying its effects remains unclear.

Purpose

This study aims to explore the therapeutic efficacy of Yangyin Yiqi Huoxue Decoction on ischemic stroke and its potential mechanism of action, particularly focusing on its modulation of the Wnt signaling pathway and impact on neuroinflammation and neural stem cells activity.

Study Design and Methods

The middle cerebral artery occlusion (MCAO) rat model and an Oxygen glucose deprivation/re-oxygenation (OGD/R) cell model were employed. In vivo experiments were conducted to investigate the therapeutic effects of the Yangyin Yiqi Huoxue Decoction at high, medium, and low dosages (3.3, 1.65, and 0.83 g/kg). The effects of Yangyin Yiqi Huoxue Decoction on neuroinflammatory cytokine levels, microglial activation, and neural stem cells proliferation and differentiation were assessed in vivo experiments. Wnt signaling components were evaluated through Quantitative Real-Time PCR and Western blot in both vivo and vitro. Additionaly, the Wnt inhibitor Dickkopf-related protein 1(DKK1) was used to confirm the pathway's involvement.

Results

The high-dose group(3.3 g/kg) of the Yangyin Yiqi Huoxue Decoction exhibited the most pronounced therapeutic effects. Yangyin Yiqi Huoxue Decoction significantly reduced pro-inflammatory cytokine levels, inhibited microglial overactivation, and enhanced neural stem cells proliferation and differentiation. It also modulated the Wnt pathway by upregulating Wnt Family Member 3A(Wnt3a) and β-catenin, while downregulating Wnt Family Member 5A(Wnt5a) and glycogen synthase kinase-3β(GSK-3β). The inhibition of Wnt signaling by Dickkopf-related protein 1(DKK1) reversed these beneficial effects, confirming Yangyin Yiqi Huoxue Decoction 's mechanism.

Conclusions

Yangyin Yiqi Huoxue Decoction exerts neuroprotective effects by suppressing neuroinflammation and promoting neural-stem-cell-mediated brain repair through the Wnt signaling pathway, positioning it as a potential candidate for ischemic stroke treatment.

Abstract Image

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养阴益气活血汤通过调节Wnt信号通路改善小胶质细胞对cis诱导的神经炎症损伤的激活机制。

背景：缺血性脑卒中是神经功能障碍的主要原因，以神经炎症和神经元凋亡为特征。Wnt信号通路在脑修复中起关键作用。养阴益气活血汤是一种传统的中草药配方，具有减轻神经炎症损伤的潜力，但其作用的确切机制尚不清楚。目的：本研究旨在探讨养阴益气活血汤对缺血性脑卒中的疗效及其可能的作用机制，重点关注其对Wnt信号通路的调节以及对神经炎症和神经干细胞活性的影响。研究设计和方法：采用大脑中动脉闭塞（MCAO）大鼠模型和氧糖剥夺/再氧合（OGD/R）细胞模型。采用体内实验研究养阴益气活血汤在高、中、低剂量（3.3、1.65、0.83 g/kg）下的治疗作用。通过体内实验观察养阴益气活血汤对大鼠神经炎性细胞因子水平、小胶质细胞活化及神经干细胞增殖分化的影响。通过定量Real-Time PCR和Western blot对体内外Wnt信号成分进行评估。此外，Wnt抑制剂dickkopf相关蛋白1（DKK1）被用来证实该途径的参与。结果：养阴益气活血汤高剂量组（3.3 g/kg）治疗效果最显著。养阴益气活血汤可显著降低促炎细胞因子水平，抑制小胶质细胞过度活化，促进神经干细胞增殖分化。它还通过上调Wnt家族成员3A（Wnt3a）和β-catenin，下调Wnt家族成员5A（Wnt5a）和糖原合成酶激酶3β(GSK-3β)来调节Wnt通路。dickkopf相关蛋白1（DKK1）对Wnt信号的抑制逆转了这些有益作用，证实了养阴益气活血汤的作用机制。结论：养阴益气活血汤通过Wnt信号通路抑制神经炎症，促进神经干细胞介导的脑修复，具有神经保护作用，是治疗缺血性脑卒中的潜在候选药物。

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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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.