Modified Huangqi Chifeng decoction alleviates IgA nephropathy inflammation and renal fibrosis via miR-146a/TLR4/NF-κB signaling modulation.

Background: Immunoglobulin A nephropathy (IgAN) is the most prevalent primary glomerulonephritis worldwide and a leading cause of end-stage renal disease, posing a significant threat to human health. Modified Huangqi Chifeng decoction (MHCD) has shown efficacy in ameliorating IgAN; however, its underlying regulatory mechanisms remain incompletely understood. Objective: To evaluate the anti-inflammatory and anti-fibrotic effects of MHCD on IgAN and elucidate its molecular mechanisms through Methods: An IgAN rat model was established. The therapeutic effects of MHCD were assessed by measuring 24-hour urinary protein, Gd-IgA1, serum biochemistry, renal pathological damage, IgA deposition, inflammatory mediators, and fibrosis levels after 8 weeks of MHCD administration. ELISA was used to quantify inflammatory mediators; Western blot and immunohistochemistry were employed to analyze protein expression; PCR was performed to determine miR-146a levels. Subsequently, lipopolysaccharide-stimulated mesangial cells were used Results: MHCD reduced urinary protein and serum Gd-IgA1 in IgAN rats, and alleviated renal IgA deposition, pathological injury, inflammation and fibrosis. Furthermore, MHCD inhibited renal expression of TLR4, MyD88, NF-κB p65 and NF-κB p-p65, and increased the level of miR-146a. Mechanistically, Conclusion: MHCD alleviates IgA nephropathy inflammation and renal fibrosis partially through upregulating miR-146a and subsequently suppressing the TLR4/NF-κB signaling pathway.