The Effect of Fanshi Tongfeng Fang on Hyperuricemia-Induced Apoptosis and Inflammation.

Abstract

Hyperuricemia (HUA) is a metabolic disorder caused by purine metabolism. Our study attempts to explore the therapeutic effect of the Fanshi Tongfeng Fang (TFF) formula against HUA and the underlying mechanism. The uric acid (UA), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatinine (Cr) levels were investigated in clinical research and in vivo experiments. The pathologic changes in kidney and xanthine oxidase (XOD) activity were measured by HE staining and kit respectively. The underlying mechanism was predicted by network pharmacology. The mRNA and protein expressions of ABCG2, URAT1, GLUT9, caspase 3, caspase 8, caspase 9, BID, Bax, Bcl-2, JUN, NLRP3, and TNF-α were detected by RT-qPCR assays and western blotting correspondingly.TFF showed a better inhibitory effect on UA, ALT, AST, and Cr levels among HUA patients than urate-lowing therapy and a higher successful treatment ratio. The UA levels, Cr value, and XOD activity were notably down-regulated after TFF treatment in HUA rats, but no measurable difference exists in ALT and AST levels by TFF treatment. Besides, TFF also markedly improved HUA-mediated renal damage and ABCG2 expressions and decreased URAT1 and GLUT9 expressions in HUA rats. Apoptosis and NOD-like receptor signaling pathways were selected according to the network pharmacology. The expressions of caspase 3, caspase 8, caspase 9, BID, Bax, JUN, NLRP3, and TNF-α were significantly decreased by TFF treatment, while Bcl-2 expression was increased by TFF treatment. TFF can alleviate HUA-induced apoptosis and inflammation via the JUN/NLRP3 pathway, which innovatively suggests the therapeutic potential of the TFF formula for HUA treatment.