Urine Metabolomics Reveals the Intervention Effects and Mechanism of Shenhua Tablets in IgA Nephropathy

Shenhua tablets (SHT), a traditional Chinese medicine (TCM), have shown significant clinical efficacy in treating IgA nephropathy (IgAN), but the underlying mechanisms are not fully understood. This study aims to elucidate the renoprotective effects of SHT on IgAN and explore the potential mechanisms of its action using metabolomics approaches. The renoprotective effects of SHT on IgAN were evaluated in a Thy-1 antibody-induced IgAN rat model. Metabolomics techniques were employed to detect and analyze urine biomarkers of IgAN, and to identify SHT targets and metabolic pathways. SHT significantly reduced the levels of 24-h urine protein (Upro), albumin-to-creatinine ratio (ACR), Interleukin 1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6), alleviated kidney tissue damage, and inhibited mesangial cell proliferation. Seventeen urine metabolites were identified as biomarkers for IgAN, 14 of which were restored by SHT. SHT primarily modulated metabolic pathways, including the tricarboxylic acid (TCA) cycle, glycolysis/gluconeogenesis, pyruvate metabolism, and β-alanine metabolism, upregulating citric acid and succinic acid while downregulating pyruvic acid, L-lactic acid, uracil, and malonic semialdehyde. SHT exerts renoprotective effects in IgAN by modulating key metabolic pathways and normalizing abnormal metabolites levels.