ROLE OF LEONURINE IN IGA NEPHROPATHY: A MECHANISTIC INSIGHT THROUGH ANIMAL MODEL

Abstract

In this study, we explored how the plant-derived alkaloid leonurine influences the progression of inflammation and fibrosis in a rat model of IgA nephropathy (IgAN), with particular emphasis on its impact on the TGF-β/SMAD signaling cascade. Thirty Sprague–Dawley rats were divided into three groups—normal controls, IgAN-induced animals, and a treatment set. IgAN was produced through repeated administration of bovine serum albumin, carbon tetrachloride, and lipopolysaccharides, and the success of model induction was validated through histological assessments showing increased glomerular IgA accumulation and upregulated fibrotic markers (TGF-β, SMAD3, α-SMA). After the disease model was established, the treatment group was given oxymatrine. Notable improvements in renal parameters were then seen. The reduced excretion of urine proteins and decreased red blood cell counts of these rats at the end of the tenth week already indicated that kidney damage had been reduced. While SGOT and SGPT remained constant, biochemical analysis also revealed decreased levels of serum creatinine, BUN, and ALB, demonstrating that this intervention protected the kidneys without appreciable hepatic strain. These results were corroborated in histopathological analyses showing better preservation of glomerular structure in the treated rats compared with the IgAN animals. Profibrotic mediators such as TGF-β, SMAD3, and α-SMA were drastically reduced by ELISA and immunofluorescence profiling, suggesting that leonurine aids in preventing the fibrotic drive linked to EMT. By the end of the tenth week, these animals manifested lower urinary protein excretion and less frequent urinary red blood cells, indicating mitigation of kidney damage. Serum creatinine, BUN, and ALB were also reduced, while there was no change in SGOT and SGPT, indicating that renal protection had been achieved without significant hepatic stress. Histopathological findings further support such observations: the glomerular structure was better preserved in treated rats when compared to IgAN animals. ELISA and immunofluorescence revealed that profibrotic mediators, namely TGF-β, SMAD3, and α-SMA, were significantly reduced, indicating the interference of leonurine with the fibrotic drive related to epithelial-to-mesenchymal transition. Overall, the results suggest that leonurine could slow IgAN progression by tempering the TGF-β/SMAD pathway and restricting pathological EMT and fibrosis. While the findings are promising, extended studies are required to clarify long-term safety and therapeutic potential.