Luling Anshen Granules, a Novel Traditional Chinese Medicine formulation, Mitigates Renal Fibrosis in Mice with Chronic Renal Failure by Suppressing the Wnt/β-catenin Signaling Pathway.

Chronic renal failure (CRF) is an escalating global health concern, imposing substantial economic and health challenges. Traditional Chinese medicine (TCM) offers potential treatments. Luling Anshen Granules (LLASG), a patented multi-herb formula used clinically for kidney disorders, have shown promise in preclinical studies, though their mechanisms remain unclear. A CRF mouse model was induced with a 2.5% adenine suspension. Mice were allocated into six groups: control, CRF model, Urotoxin Qing Granules (UCG) positive control, and three groups treated with LLASG at doses of 2.5, 5, and 10 g/kg. Renal function was evaluated after 4 weeks using blood urea nitrogen, serum creatinine, and 24-hour urinary protein measurements. Renal tissues underwent examination through hematoxylin and eosin, Masson, and TUNEL staining techniques. Protein and gene expressions were analyzed by Western blot, RT-qPCR, immunohistochemistry, and immunofluorescence. A β-catenin knockdown experiment was conducted, and LLASG’s biocompatibility and safety were evaluated in cardiac and hepatic tissues. LLASG enhanced renal function in a dose-dependent fashion, reducing serum blood urea nitrogen and creatinine levels by approximately 30–40% at the highest dose compared with CRF mice, decreased renal tissue damage and apoptosis, and alleviated renal inflammation through NF-κB pathway inhibition. It mitigated renal fibrosis by suppressing the Wnt/β-catenin pathway. β-catenin knockdown diminished the therapeutic effects of LLASG, confirming its mechanistic role. LLASG produced no observable cardiac or hepatic toxicity under the conditions tested, indicating acceptable short-term biocompatibility. Overall, LLASG ameliorates renal dysfunction, inflammation, and fibrosis in CRF mice by suppressing the Wnt/β-catenin pathway.