Shijie Li, Shiyu Zhang, Lin Cui, Yue Li, Yuqi Wang, Youping Wang
This study provides the first systematic review evaluating AS-IV across etiologically diverse models of renal fibrosis, showing its broad-spectrum anti-fibrotic pharmacological effects. The synthesized evidence suggests that these renoprotective effects may be mediated through multi-target modulation, including mitigating inflammation and oxidative stress, modulating autophagy and apoptosis, and reducing extracellular matrix (ECM) accumulation. Nevertheless, given the significant heterogeneity and overall suboptimal methodological quality of the included studies, these positive findings should be interpreted with caution.
BACKGROUND: Renal fibrosis is the principal pathological hallmark of progressive chronic kidney disease (CKD). However, the clinical availability of effective, targeted anti-fibrotic therapeutics remains severely constrained. Astragaloside IV (AS-IV), a predominant bioactive metabolite isolated from Astragali Radix, has exhibited substantial renoprotective and anti-fibrotic properties in diverse preclinical models.
MATERIALS AND METHODS: We systematically searched eight electronic databases (PubMed, Web of Science, Embase, ProQuest, CNKI, SinoMed, VIP, and Wanfang Data) from inception to 30 November 2025, to identify relevant in vivo studies. Risk of bias was assessed using the SYRCLE tool. Statistical analyses were performed using Review Manager 5.3 and Stata 18.0.
RESULTS: A total of 34 studies involving 769 animals were included. Compared with the control group, AS-IV treatment significantly reduced the levels of serum creatinine (Scr), blood urea nitrogen (BUN), proteinuria, transforming growth factor-β1 (TGF-β1), fibronectin, and α-smooth muscle actin (α-SMA) (all P < 0.0001). Subgroup analyses revealed that intragastric dose was a source of heterogeneity for Scr; publication year for BUN; treatment duration for TGF-β1; and the underlying animal disease model alongside treatment duration for α-SMA. Dose-response analyses revealed that Scr, BUN, TGF-β1, fibronectin, and α-SMA showed overall negative dose-dependent trends. In addition, AS-IV significantly modulated the expression of other indicators related to fibrosis, oxidative stress, and inflammatory responses. Methodologically, the overall quality of the included studies was suboptimal, and there was considerable statistical heterogeneity. Additionally, the presence of publication bias cannot be definitively excluded. These results suggest that AS-IV holds renoprotective potential in animal models of renal fibrosis; however, these results should be interpreted prudently.
CONCLUSION: This study provides the first systematic review evaluating AS-IV across etiologically diverse models of renal fibrosis, showing its broad-spectrum anti-fibrotic pharmacological effects. The synthesized evidence suggests that these renoprotective effects may be mediated through multi-target modulation, including mitigating inflammation and oxidative stress, modulating autophagy and apoptosis, and reducing extracellular matrix (ECM) accumulation. Nevertheless, given the significant heterogeneity and overall suboptimal methodological quality of the included studies, these positive findings should be interpreted with caution.
SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261372263, identifier CRD420261372263.