Zhang Shujuan, Xue Yan, Zhang Xing, Chen Feng, Li Yalan, Zhang Wei
Department of Pulmonary Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Front Pharmacol. 2025 Jul 31;16:1564290. doi: 10.3389/fphar.2025.1564290. eCollection 2025.
Pulmonary fibrosis (PF) remains a devastating disease with limited therapeutic options. Astragaloside IV (AS-IV), a natural compound from Astragalus mongholicus (AM), has shown promise as a possible treatment for fibrosis. However, a systematic evaluation of its therapeutic efficacy and underlying mechanisms is lacking. This meta-analysis synthesizes preclinical evidence to assess the therapeutic potential of AS-IV in PF.
Preclinical literature published before 16 August 2024, was systematically retrieved and screened across eight major databases, including PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wan Fang Data Knowledge Service Platforms (Wanfang), China Science and Technology Journal Database (CQVIP), and China Biological Medicine Database (CBM). The risk of bias was assessed using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool, and meta-analysis was conducted using STATA 18.0. The underlying mechanisms were also summarized.
This systematic review and meta-analysis encompassed 23 animal studies comprising a total of 518 animals. The methodological quality scores of the included studies ranged from 3 to 6 points. The overall analysis demonstrated that AS-IV significantly reduced key indicators of PF in animal models, including PF score [SMD = -2.56, 95% CI (-3.47, -1.65), 0.01, 72.6%]; pulmonary inflammation scores [SMD = -2.18, 95% CI (-3.09, -1.27), 0.01, 70.2%]; hydroxyproline (HYP) content [SMD = -4.31, 95% CI (-5.67, -2.95), 0.01, 83.1%]; lung index [SMD = -3.43, 95% CI (-4.75, -2.10), 0.01, 79.5%]; and α-smooth muscle actin (α-SMA) levels [SMD = -4.79, 95% CI (-6.01, -3.56), 0.01, 55.3%]. Sensitivity analyses confirmed the robustness of these results. However, the asymmetry observed in the funnel plot suggests potential publication bias. Further analysis revealed that AS-IV modulates key biomarkers involved in the epithelial-mesenchymal transition (EMT) process and mitigates extracellular matrix (ECM) remodeling. Additionally, AS-IV reduces the levels of inflammatory markers and oxidative stress indicators, thereby exerting a significant intervention in PF.
This meta-analysis demonstrates that AS-IV consistently ameliorates BLM-induced PF through multiple mechanisms, including inhibition of EMT, ECM remodeling, inflammation, and oxidative stress. These findings support further investigation of AS-IV as a multi-target therapeutic agent for PF.
identifier CRD42024604432.
肺纤维化（PF）仍然是一种具有严重破坏性且治疗选择有限的疾病。黄芪甲苷IV（AS-IV）是一种从蒙古黄芪（AM）中提取的天然化合物，已显示出作为纤维化潜在治疗方法的前景。然而，目前缺乏对其治疗效果和潜在机制的系统评估。本荟萃分析综合临床前证据，以评估AS-IV在PF中的治疗潜力。
系统检索并筛选了截至2024年8月16日发表的临床前文献，检索范围涵盖八个主要数据库，包括PubMed、Embase、Web of Science、Cochrane图书馆、中国知网（CNKI）、万方数据知识服务平台（万方）、中国科技期刊数据库（维普）和中国生物医学数据库（CBM）。使用实验室动物实验系统评价中心（SYRCLE）工具评估偏倚风险，并使用STATA 18.0进行荟萃分析。同时总结了潜在机制。
本系统评价和荟萃分析纳入了23项动物研究，共518只动物。纳入研究的方法学质量得分在3至6分之间。总体分析表明，AS-IV显著降低了动物模型中PF的关键指标，包括PF评分[标准化均数差（SMD）=-2.56，95%置信区间（CI）（-3.47，-1.65），P<0.01，I²=72.6%]；肺部炎症评分[SMD=-2.18，95%CI（-3.09，-1.27），P<0.01，I²=70.2%]；羟脯氨酸（HYP）含量[SMD=-4.31，95%CI（-5.67，-2.95），P<0.01，I²=83.1%]；肺指数[SMD=-3.43，95%CI（-4.75，-2.10），P<0.01，I²=79.5%]；以及α-平滑肌肌动蛋白（α-SMA）水平[SMD=-4.79，95%CI（-6.01，-3.56），P<0.01，I²=55.3%]。敏感性分析证实了这些结果的稳健性。然而，漏斗图中观察到的不对称性表明可能存在发表偏倚。进一步分析显示，AS-IV调节上皮-间质转化（EMT）过程中涉及的关键生物标志物，并减轻细胞外基质（ECM）重塑。此外，AS-IV降低炎症标志物和氧化应激指标的水平，从而对PF产生显著干预作用。
本荟萃分析表明，AS-IV通过多种机制持续改善博来霉素诱导的PF，包括抑制EMT、ECM重塑、炎症和氧化应激。这些发现支持进一步研究将AS-IV作为PF的多靶点治疗药物。
标识符CRD42024604432。
