中药调控Wnt/β-Catenin信号通路治疗缺血性脑卒中研究进展

doi:10.19803/j.1672-8629.20240653

摘要/Abstract

摘要： 目的综述Wnt/β-Catenin信号通路在急性缺血性脑卒中（IS）所发挥的作用,总结中药复方及单体通过Wnt/β-Catenin信号通路对IS发挥治疗作用的机制。方法通过检索国内外相关文献,对现有中药复方及其单体进行归纳总结,对未来研究方向进行预测。结果中药可以通过靶向调控Wnt/β-Catenin信号通路,通过抗炎、抗氧化应激、抗神经细胞凋亡及促进血管生成等方面有效减轻IS导致的脑损伤,为IS的治疗提供新思路。结论在对IS的治疗过程中,中药可通过Wnt/β-Catenin信号通路发挥治疗效果,但其在临床上的应用及其机制仍需更深入研究。

关键词: 缺血性脑卒中, Wnt/β-Catenin信号通路, 中医药, 研究进展

Abstract: Objective To study the role of the Wnt/β-catenin signaling pathway in acute ischemic stroke (IS), and to summarize the mechanisms by which traditional Chinese medicine formulas and monomers exert therapeutic effects on IS through the Wnt/β-catenin signaling pathway. Methods By searching related literature at home and abroad, traditional Chinese medicine formulas and their monomers currently available were summarized, and future developments were predicted. Results Traditional Chinese medicine could effectively alleviate brain damage caused by IS by targeting the Wnt/β-catenin signaling pathway, including anti-inflammation, antioxidant stress, anti neuronal apoptosis, and promotion of angiogenesis. Conclusion In the treatment of IS, traditional Chinese medicine can exert a good effect through the Wnt/β-catenin signaling pathway.

Key words: Ischemic Stroke, Wnt/β-Catenin Signaling Pathway, Traditional Chinese Medicine, Research Progress

中图分类号:

R994.11
R743

刘苏杰, 闫嘉鹤, 阮佳鑫, 王晨, 王晓凡, 刘树民, 白雪. 中药调控Wnt/β-Catenin信号通路治疗缺血性脑卒中研究进展[J]. 中国药物警戒, 2024, 21(12): 1388-1392.

LIU Sujie, YAN Jiahe, RUAN Jiaxin, WANG Chen, WANG Xiaofan, LIU Shumin, BAI Xue. Research Progress in Regulation of Wnt/β-Catenin Signaling Pathway by TCM in the Treatment of Ischemic Stroke[J]. Chinese Journal of Pharmacovigilance, 2024, 21(12): 1388-1392.

导出引用管理器 EndNote|Ris|BibTeX

链接本文: https://zgywjj.magtechjournal.com/CN/10.19803/j.1672-8629.20240653

https://zgywjj.magtechjournal.com/CN/Y2024/V21/I12/1388

参考文献

[1] SUN J, LIU Y, XI Y, et al.Multi-Grained Contrastive Representation Learning for Label-Efficient Lesion Segmentation And Onset Time Classification Of Acute Ischemic Stroke[J]. Med Image Anal, 2024, 97: 103250.
[2] PENG B, MOHAMMED FS, TANG X, et al.Nanotechnology Approaches to Drug Delivery for the Treatment of Ischemic Stroke[J]. Bioact Mater, 2024, 43: 145-161.
[3] IRIE T, MATSUDA T.In Vivo Direct Neuronal Conversion as A Therapeutic Strategy for Ischemic Stroke[J]. Neural Regeneration Research, 2025, 20(8): 2309-2310.
[4] FESKE SK.Ischemic Stroke[J]. The American Journal of Medicine, 2021, 134(12): 1457-1464.
[5] HE X, WU M, CHEN L, et al.APMCG-1 Attenuates Ischemic Stroke Injury by Reducing Oxidative Stress and Apoptosis and Promoting Angiogenesis via Activating PI3K/AKT Pathway[J]. J Biomedicine & Pharmacotherapy, 2024, 180: 117506.
[6] TUO QZ, ZHANG ST, LEI P.Mechanisms of Neuronal Cell Death in Ischemic Stroke and Their Therapeutic Implications[J]. Medicinal Research Reviews, 2022, 42(1): 259-305.
[7] PAN R, ZHANG M, ZHENG XY, et al. The Role of wnt/β-Catenin Signaling Pathway in the Apoptotic Process of Ischemic Stroke[J/OL]. Chinese Journal of Comparative Medicine(中国比较医学杂志), (2024-10-08)[2024-11-10]. http://kns.cnki.net/kcms/detail/11.4822.R.20241008.1042.013.html.
[8] HUANG Y, ZHANG Z, XU Y, et al.ARMC10 Regulates Mitochondrial Dynamics and Affects Mitochondrial Function via the Wnt/β-Catenin Signalling Pathway Involved in Ischaemic Stroke[J]. Journal of Cellular and Molecular Medicine, 2024, 28(12): e18449.
[9] GU X, DONG M, XIA S, et al.γ-Glutamylcysteine Ameliorates Blood-Brain Barrier Permeability and Neutrophil Extracellular Traps Formation after Ischemic Stroke by Modulating Wnt/β-Catenin Signalling in Mice[J]. European Journal of Pharmacology, 2024, 969: 176409.
[10] WU L, CHENG Y, WANG R, et al.NDRG2 Regulates Glucose Metabolism and Ferroptosis of OGD/R-Treated Astrocytes by the Wnt/β-Catenin Signaling[J]. Journal of Biochemical and Molecular Toxicology, 2024, 38(9): e23827.
[11] XU J, LIU S, XU L, et al.Therapeutic Strategies for Ischemic Stroke: Modulating the Adult Neural Stem Cell Niche through the Wnt/β-Catenin Pathway[J]. Journal of Integrative Neuroscience, 2024, 23(7): 131.
[12] WANG N, CHEN J, DANG Y, et al.Research Progress of Traditional Chinese Medicine in the Treatment of Ischemic Stroke by Regulating Mitochondrial Dysfunction[J]. Life Sciences, 2024, 357: 123045.
[13] AN H, ZHOU B, JI X.Mitochondrial Quality Control in Acute Ischemic Stroke[J]. Journal of Cerebral Blood Flow and Metabolism, 2021, 41(12): 3157-3170.
[14] CHEN X, YAO N, MAO Y, et al.Activation of the Wnt/β-Catenin/CYP1B1 Pathway Alleviates Oxidative Stress and Protects the Blood-Brain Barrier under Cerebral Ischemia/Reperfusion Conditions[J]. Neural Regeneration Research, 2024, 19(7): 1541-1547.
[15] DING J, LEE S J, VLAHOS L, et al.Therapeutic Blood-Brain Barrier Modulation and Stroke Treatment by a Bioengineered FZD(4)-Selective WNT Surrogate in Mice[J]. Nature Communications, 2023, 14(1): 2947.
[16] JI Y B, WANG TX, GAO Q, et al.Normalization of Non-Canonical Wnt Signalings Does Not Compromise Blood-Brain Barrier Protection Conferred by Upregulating Endothelial Wnt/β-Catenin Signaling Following Ischemic Stroke[J]. CNS Neuroscience & Therapeutics, 2021, 27(9): 1085-1096.
[17] LI MQ, ZHAO XL, GAO XY, et al.Progress in Research on the Relationship between Epithelial-Mesenchymal Transition and Liver Fibrosis[J]. Chinese Journal of Pharmacovigilance(中国药物警戒), 2024, 21(4): 464-468, 472.
[18] LIU C, SUN S, XIE J, et al.GLP-1R Agonist Exendin-4 Protects Against Hemorrhagic Transformation Induced by rtPA after Ischemic Stroke via the Wnt/β-Catenin Signaling Pathway[J]. Molecular Neurobiology, 2022, 59(6): 3649-3664.
[19] MO Z, ZENG Z, LIU Y, et al.Activation of Wnt/Beta-Catenin Signaling Pathway as A Promising Therapeutic Candidate for Cerebral Ischemia/Reperfusion Injury[J]. Frontiers in Pharmacology, 2022, 13: 914537.
[20] SONG S, HUANG H, GUAN X, et al.Activation of Endothelial Wnt/β-Catenin Signaling by Protective Astrocytes Repairs BBB Damage in Ischemic Stroke[J]. Progress in Neurobiology, 2021, 199: 101963.
[21] HAN Y, LIN N.Systemic Inflammatory Response Index and the Short-Term Functional Outcome of Patients with Acute Ischemic Stroke: A Meta-Analysis[J]. Neurology and Therapy, 2024, 13(5): 1431-1451.
[22] LI Y, XU X, WU X, et al.Cell Polarization in Ischemic Stroke: Molecular Mechanisms and Advances[J]. Neural Regeneration Research, 2025, 20(3): 632-645.
[23] WANG F, XIA J, ZHAO B.Effects of Edaravone on Neuronal Proliferation in Acute Stroke Rats Based on Wnt/β-Catenin Signaling Pathway[J]. Journal of Brain and Neurological Diseases(脑与神经疾病杂志), 2021, 29(7): 406-411.
[24] ZHANG H, DU D, GAO X, et al.PFT-α Protects The Blood-Brain Barrier through the Wnt/β-Catenin Pathway after Acute Ischemic Stroke[J]. Functional & Integrative Genomics, 2023, 23(4): 314.
[25] OUYANG Y, HU S, CHANG M, et al.Catecholamines-Based Myocardial Injury after Acute Ischemic Stroke and Effects of Naoxintong Capsule Therapy[J]. Phytomedicine, 2024, 132: 155697.
[26] YANG X, WANG S, XUE W, et al. Nattokinase's Neuroprotective Mechanisms in Ischemic Stroke: Targeting Inflammation, Oxidative Stress,Coagulation[J/OL]. Antioxidants & Redox Signaling, (2024-09-05)[2024-11-10]. https://pubmed.ncbi.nlm.nih.gov/39135387/.
[27] YAO NN.WNB-CATENINCYP1B1 Axis Regulates the Effect of Oxidative Stress on the Expression of Endothelium Blood-Brain Barrier Protein Under OGDRR[D]. Fuzhou: Fuzhou Medical University, 2022.
[28] LI XX.Based on Wnt/β-Catenin Signaling Pathway, the Effect of Electroacupuncture Serum on the Injury of Neurovascular Unit Model Induced by Glucose and Hypoxia in vitro Was Investigated[D]. Hefei: Anhui University of Traditional Chinese Medicine, 2022.
[29] ZHU ZH.Application and Mechanism of Neural Stem Cell Exosome-Based Therapy in Ischemic Stroke[D]. Nanjing: Southeast University, 2022.
[30] MA YG, WANG XC, WANG XB, et al.Research Progress of Chinese Herbs Regulating mTOR Signaling Pathway in the Treatment of Ischemic Stroke[J]. Chinese Journal of Experimental Formulae(中国实验方剂学杂志), 2024, 30(11): 265-272.
[31] WANG LP, PAN J, LI Y, et al.Oligodendrocyte Precursor Cell Transplantation Promotes Angiogenesis and Remyelination via Wnt/β-Catenin Pathway in A Mouse Model of Middle Cerebral Artery Occlusion[J]. Journal of Cerebral Blood Flow and Metabolism, 2022, 42(5): 757-770.
[32] NIU YQ, QIN HW, GUO N, et al.Progress in the Study on the Mechanism of Wnt/β-Catenin Signaling Pathway in Angiogenesis after Cerebral Infarction[J]. Chinese Journal of Gerontology(中国老年学杂志), 2023, 43(7): 1787-1791.
[33] LI W, WEI D, XIE X, et al.Dl-3-n-Butylphthalide Regulates the Ang-1/Ang-2/Tie-2 Signaling Axis to Promote Neovascularization in Chronic Cerebral Hypoperfusion[J]. Biomedicine & Pharmacotherapy, 2019, 113: 108757.
[34] XIE M, CHEN ZG, JYU WH.Shuxuening Injection Protects Rats from Ischemic Brain Injury via Wnt/β-Catenin Signaling Pathway[J]. Chinese Journal of Neuroanatomy(神经解剖学杂志), 2024, 40(1): 91-97.
[35] LI Z, WANG H, XIAO G, et al.Recovery of Post-Stroke Cognitive and Motor Deficiencies by Shuxuening Injection via Regulating Hippocampal BDNF-Mediated Neurotrophin/Trk Signaling[J]. Biomedicine & Pharmacotherapy, 2021, 141: 111828.
[36] JIANG LM, SANG F, LIU XZ, et al.Protective Effect of Qi-Supplementing and Blood-Activating Therapy on Cerebral Neurons in Rats with Acute Ischemic Stroke Based on Wnt/β-Catenin Signaling Pathway[J]. Journal of Guangzhou University of Traditional Chinese Medicine(广州中医药大学学报), 2022, 39(6): 1358-1365.
[37] ZHANG YB.Based on Wnt/β-Catenin Signaling Pathway, to Explore the Mechanism of Jianpi Yizhi Method in Regulating the Proliferation of NSCS in MCAO Rats[D]. Fuzhou: Fujian University of Traditional Chinese Medicine, 2018.
[38] ZHAO S, SUN T, ZHANG M, et al.Efficacy and Safety of Shenmai Injection for Acute Ischemic Stroke: A Systematic Review and Meta-Analysis[J]. Frontiers in Pharmacology, 2024, 15: 1394936.
[39] LI XL, DAI ZZ.Clinical Study of Shenmai Injection in the Treatment of Acute Ischemic Stroke[J]. Electronic Journal of Modern Medicine and Health Research(现代医学与健康研究电子杂志), 2022, 6(10): 24-27.
[40] GENG JW.Wnt/β-Catenin Pathway Mediates Ischemic Tolerance of Shenmai Injection and Down-Regulates Autophagy[D]. Suzhou: Suzhou University, 2018.
[41] ZHANG FR, LI QQ, WANG JQ, et al . Effect of Dandeng Tongnao Capsule on Intestinal Microflora in Rats Cerebral Ischemia-Reperfusion[J]. Herald of Medicine(医药导报), 2022, 41(8): 1121-1129.
[42] HUANG Q, QI J, GAO Z, et al.Chemical Composition and Protective Effect of Cerebrospinal Fluid of Dan-Deng-Tong-Nao Capsules on Brain Microvascular Endothelial Cells Injured by OGD/R[J]. Journal of Ethnopharmacology, 2022, 283: 114705.
[43] ZHANG LM.Study on the Effect of Damrong Xingnao Fang on the Increase of NSCS and the Expression of WNT-1, WNT-3A, β-Catenin and Gsk-3β in IR Rats[D]. Changsha: Hunan University of Traditional Chinese Medicine, 2015.
[44] ZHANG M, ZHANG Y, PENG J, et al.Gastrodin Against Oxidative Stress-Inflammation Crosstalk via Inhibiting mtDNA/TLR9 and JAK2/STAT3 Signaling to Ameliorate Ischemic Stroke Injury[J]. J International Immunopharmacology, 2024, 141: 113012.
[45] QIU CW, LIU ZY, ZHANG FL, et al.Post-Stroke Gastrodin Treatment Ameliorates Ischemic Injury and Increases Neurogenesis and Restores the Wnt/β-Catenin Signaling in Focal Cerebral Ischemia in Mice[J]. Brain Research, 2019, 1712: 7-15.
[46] WANG W.Drug and Electrical Stimulation Rehabilitation Therapy Based on Nerve Regeneration and Repair Strategy[J]. Chinese Journal of Pharmacology and Toxicology(中国药理学与毒理学杂志), 2021, 35(9): 698-699.
[47] SUN FL, WANG W, ZUO W, et al.Promoting Neurogenesis via Wnt/β-Catenin Signaling Pathway Accounts for the Neurorestorative Effects of Morroniside against Cerebral Ischemia Injury[J]. European Journal of Pharmacology, 2014, 738: 214-221.
[48] BUAIJIER·AILI, AIERGULI·AMT, KAREYEMU·KDE, et al. Emodin attenuates Ischemic Stroke in Rats by Regulating Wnt/β-Catenin Signaling Pathway[J]. Journal of Brain and Nervous Diseases(脑与神经疾病杂志), 2023, 31(4): 224-230.
[49] CHEN D, WEN CM, LI XX, et al.Effect of Lycium Barbarum Polysaccharide on the Apoptosis of Neurons in Rats with Cerebral Infarction by Regulating PPAR γ/MAPK/NF-κb Signaling Pathway[J]. Chinese Journal of Gerontology(中国老年学杂志), 2024, 44(10): 2455-2462.
[50] ZHAO Q.Effects of Lycium Barbarum Polysaccharide on Wnt/β-Catenin Signaling Pathway in Hyperglycemia-Induced Cerebral Ischemia-Reperfusion Injury[D]. Yinchuan: Ningxia Medical University, 2019.