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
摘要
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.