Renal protective effects and mechanisms of Astragalus membranaceus for diabetic kidney disease in animal models: An updated systematic review and meta-analysis

Astragalus membranaceus (AM) shows potential therapeutic benefits for managing diabetic kidney disease (DKD), a leading cause of kidney failure with no cure. However, its comprehensive effects on renal outcomes and plausible mechanisms remain unclear. This systematic review and meta‐analysis aimed to synthesize the effects and mechanisms of AM on renal outcomes in DKD animal models. Seven electronic databases were searched for animal studies until September 2023. Risk of bias was assessed based on SYRCLE's Risk of Bias tool. Standardized mean difference (SMD) or mean difference (MD) were estimated for the effects of AM on serum creatinine (SCr), blood urea nitrogen (BUN), albuminuria, histological changes, oxidative stress, inflammation, fibrosis and glucolipids. Effects were pooled using random‐effects models. Heterogeneity was presented as I2. Subgroup analysis investigated treatment- and animal-related factors for renal outcomes. Publication bias was assessed using funnel plots and Egger's test. Sensitivity analysis was performed to assess the results’ robustness. RevMan 5.3 and Stata MP 15 software were used for statistical analysis. Forty studies involving 1,543 animals were identified for analysis. AM treatment significantly decreased SCr (MD = –19.12 μmol/L, 95% CI: –25.02 to –13.23), BUN (MD = –6.72 mmol/L, 95% CI: –9.32 to –4.12), urinary albumin excretion rate (SMD = –2.74, 95% CI: –3.57, –1.90), histological changes (SMD = –2.25, 95% CI: –3.19 to –1.32). AM treatment significantly improved anti-oxidative stress expression (SMD = 1.69, 95% CI: 0.97 to 2.41), and decreased inflammation biomarkers (SMD = –3.58, 95% CI: –5.21 to –1.95). AM treatment also decreased fibrosis markers (i.e. TGF-β1, CTGF, collagen IV, Wnt4 and β-catenin) and increased anti-fibrosis marker BMP-7. Blood glucose, lipids and kidney size were also improved compared with the DM control group. AM could improve renal outcomes and alleviate injury through multiple signaling pathways. This indicates AM may be an option to consider for the development of future DKD therapeutics.