Zuogui Pill Promotes Neurovascular Regeneration and Corticospinal Tract Remodeling After Ischemic Stroke.

IF 4.7 2区医学 Q1 CHEMISTRY, MEDICINAL

Drug Design, Development and Therapy Pub Date : 2025-05-21 eCollection Date: 2025-01-01 DOI:10.2147/DDDT.S518696

Dan Wu, Xiaohui Yan, Siqi Mei, Hao Hua, Xiaoyu Fei, Xinyu Xu, Yan Liu, Minghua Wu, Jian Zhu, Wenlei Li

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引用次数: 0

Abstract

Background: Ischemic stroke (IS) remains a leading cause of long-term disability. Neurovascular regeneration and remodeling of the corticospinal tracts are essential for neurological functional recovery. Zuogui pill (ZGP) has good efficacy in treating cerebral ischemia, but the mechanism remains unclear.

Purpose: To investigate the effects of ZGP on angiogenesis, neurogenesis, corticospinal tract (CST) remodeling, and further evaluate its mechanisms of action in mice with ischemic stroke.

Methods: Network pharmacology was used to analyze the active components, related targets, and mechanisms of ZGP's action in promoting neurovascular regeneration after ischemic stroke. Using a photothrombotic (PT) stroke mouse model, ZGP's effects on neurological recovery were assessed using behavioral tests. Angiogenesis and neurogenesis were evaluated by immunofluorescence of glucose transporter type 1(Glut-1) +/5-bromo-20-deoxyuridine (BrdU) + vessels and doublecortin (DCX)+/BrdU+ cells. CST remodeling was evaluated through diffusion tensor imaging (DTI). The levels of vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), and mammalian target of rapamycin (mTOR) expression were tested by Western blot.

Results: Network pharmacology identified 94 active ingredients and 83 overlapping targets related to IS and neurovascular regeneration. mTOR was identified as one of the core targets. Behavioral tests demonstrated ZGP significantly reduced error rates in irregular ladder walking (ZGP-H vs Stroke: p=0.003) and shortened sticker removal time (ZGP-H vs Stroke: p=0.003). Immunofluorescence revealed ZGP enhanced angiogenesis (Glut-1+/BrdU+ vessels: ZGP-H vs Stroke, p=0.018), neural progenitor cell proliferation and migration (BrdU+/DCX+ cells: ZGP-H vs Stroke: p=0.014). DTI showed increased fractional anisotropy (FA) in ipsilateral CST regions (ZGP-H vs Stroke: 0.001

Conclusion: ZGP promotes neurovascular regeneration, CST remodeling, and neurological function recovery after ischemic stroke. The positive impacts of ZGP are linked to heightened VEGF and BDNF expression and the activation of the mTOR pathway.

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左归丸促进缺血性脑卒中后神经血管再生和皮质脊髓束重构。

背景：缺血性脑卒中（IS）仍然是导致长期残疾的主要原因。神经血管再生和皮质脊髓束重塑是神经功能恢复的必要条件。左归丸治疗脑缺血有较好的疗效，但其作用机制尚不清楚。目的：研究ZGP对缺血性脑卒中小鼠血管生成、神经发生、皮质脊髓束（CST）重构的影响，并进一步探讨其作用机制。方法：采用网络药理学方法，分析中草药提取物促进缺血性脑卒中后神经血管再生的活性成分、相关靶点及作用机制。采用光血栓性（PT）中风小鼠模型，通过行为测试评估ZGP对神经恢复的影响。采用免疫荧光法观察1型葡萄糖转运体(Glut-1) +/5-溴-20-脱氧尿苷(BrdU) +血管和双皮质素(DCX)+/BrdU+细胞的血管新生和神经新生情况。通过弥散张量成像（DTI）评估CST重构。Western blot检测各组大鼠血管内皮生长因子（VEGF）、脑源性神经营养因子（BDNF）和雷帕霉素靶蛋白（mTOR）的表达水平。结果：网络药理学鉴定出IS与神经血管再生相关的94种有效成分和83种重叠靶点。mTOR被确定为核心目标之一。行为测试表明，ZGP显著降低了不规则梯子行走的错误率（ZGP- h vs中风：p=0.003），缩短了贴纸移除时间（ZGP- h vs中风：p=0.003）。免疫荧光显示ZGP增强血管生成（Glut-1+/BrdU+血管：ZGP- h vs卒中，p=0.018），神经祖细胞增殖和迁移（BrdU+/DCX+细胞：ZGP- h vs卒中：p=0.014）。DTI显示同侧CST区分数各向异性（FA）增加（ZGP- h vs卒中：0.001）结论：ZGP促进缺血性卒中后神经血管再生、CST重构和神经功能恢复。ZGP的积极作用与VEGF和BDNF表达的增加以及mTOR通路的激活有关。

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

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.