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用于肌萎缩侧索硬化症SOD1小鼠的草药:临床前证据及可能的免疫机制。

Herbal medicines for SOD1 mice of amyotrophic lateral sclerosis: preclinical evidence and possible immunologic mechanism.

作者信息

Yang Jiang-Li, Wu Jing-Ying, Liu Jing-Jing, Zheng Guo-Qing

机构信息

Department of Neurology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China.

出版信息

Front Immunol. 2024 Sep 17;15:1433929. doi: 10.3389/fimmu.2024.1433929. eCollection 2024.

DOI:10.3389/fimmu.2024.1433929
PMID:39355247
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11442286/
Abstract

Currently, there is no cure or effective treatment for Amyotrophic Lateral Sclerosis (ALS). The mechanisms underlying ALS remain unclear, with immunological factors potentially playing a significant role. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), a systematic review of preclinical studies was conducted, searching seven databases including PubMed, covering literature from the inception of the databases to April 10, 2024. Methodological quality of the included literature was assessed using CAMARADES, while the risk of bias in the included studies was evaluated using SYRCLE's ROB tool. Review Manager 5.4.1 statistical software was used for meta-analysis of the outcomes. The scoping review followed the Joanna Briggs Institute Methodological Guidelines and reporting of this review followed the PRISMA-extension for Scoping Reviews (PRISMA -ScR) checklist to explore the immunological mechanisms of Herbal Medicine (HM) in treating ALS. This systematic review and meta-analysis involved 18 studies with a total of 443 animals. The studies scored between 4 to 8 for methodological quality and 3 to 7 for risk of bias, both summing up to 10.A remarkable effects of HM in ALS mice, including onset time(Standardized Mean Difference(SMD): 1.75, 95% Confidence Interval(CI) (1.14 ~ 2.36), Z = 5.60, < 0.01), survival time(SMD = 1.42, 95% CI (0.79 ~ 2.04), Z = 4.44, P < 0.01), stride length(SMD=1.90, 95% CI (1.21 to 2.59), Z = 5.39, P < 0.01) and duration time (Mean Difference(MD)=6.79, 95% CI [-0.28, 13.87], Z=1.88, P =0.06), showing HM's certain efficiency in treating ALS mice. The scoping review ultimately included 35 articles for review. HMs may treat ALS through mechanisms such as combating oxidative stress, excitatory amino acid toxicity, and calcium cytotoxicity, understanding and exploring the mechanisms will bring hope to patients. Individual herbs and their formulations within HM address ALS through a variety of immune pathways, including safeguarding the blood-brain barrier, countering neuroinflammation, impeding complement system activation, mitigating natural killer cell toxicity, and regulating T cell-mediated immune pathways. The preclinical evidence supports the utilization of HM as a conventional treatment for ALS mice. Growing evidence indicates that HM may potentially delay neurological degeneration in ALS by activating diverse signaling pathways, especially immune pathways.

摘要

目前,肌萎缩侧索硬化症(ALS)尚无治愈方法或有效治疗手段。ALS的潜在发病机制仍不清楚,免疫因素可能起着重要作用。本研究遵循系统评价与Meta分析的首选报告项目(PRISMA),对临床前研究进行了系统评价,检索了包括PubMed在内的7个数据库,涵盖从数据库建立至2024年4月10日的文献。采用CAMARADES评估纳入文献的方法学质量,同时使用SYRCLE的ROB工具评估纳入研究的偏倚风险。使用Review Manager 5.4.1统计软件对结果进行Meta分析。本范围综述遵循乔安娜·布里格斯研究所方法指南,本综述的报告遵循范围综述的PRISMA扩展版(PRISMA -ScR)清单,以探索草药(HM)治疗ALS的免疫机制。本系统评价和Meta分析纳入了18项研究,共涉及443只动物。这些研究的方法学质量得分在4至8分之间,偏倚风险得分在3至7分之间,总分均为10分。HM对ALS小鼠有显著疗效,包括发病时间(标准化均数差(SMD):1.75,95%置信区间(CI)(1.142.36),Z=5.60,P<0.01)、生存时间(SMD=1.42,95%CI(0.792.04),Z=4.44,P<0.01)、步幅(SMD=1.90,95%CI(1.21至2.59),Z=5.39,P<0.01)和持续时间(均数差(MD)=6.79,95%CI[-0.28,13.87],Z=1.88,P=0.06),表明HM在治疗ALS小鼠方面具有一定疗效。范围综述最终纳入35篇文献进行综述。草药可能通过对抗氧化应激、兴奋性氨基酸毒性和钙细胞毒性等机制治疗ALS,了解和探索这些机制将给患者带来希望。草药中的单味药及其配方通过多种免疫途径治疗ALS,包括保护血脑屏障、对抗神经炎症、阻止补体系统激活、减轻自然杀伤细胞毒性以及调节T细胞介导的免疫途径。临床前证据支持将草药作为ALS小鼠的常规治疗方法。越来越多的证据表明,草药可能通过激活多种信号通路,尤其是免疫通路,潜在地延缓ALS患者的神经退行性变。

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