Bu Shen Huo Xue Formula ameliorates chronic kidney disease and suppresses NLRP3 inflammasome-mediated pyroptosis and renal fibrosis.

BACKGROUND: Bu Shen Huo Xue Formula (BSHX) is used in traditional Chinese medicine for chronic kidney disease (CKD), but its pharmacological mechanisms remain unclear. This study investigated whether effects of BSHX against CKD are associated with modulation of NLRP3 inflammasome-mediated pyroptosis and the inflammation-fibrosis axis. METHODS: BSHX constituents were characterized by UPLC-MS/MS. Network pharmacology and molecular docking were used to predict potential targets. CKD was induced in mice by unilateral nephrectomy with contralateral ischemia-reperfusion injury. Mice received low- or high-dose BSHX or losartan potassium. Renal function, histopathology, fibrosis, inflammatory responses, and pyroptosis-related markers were assessed by serum biochemistry, staining, Western blotting, qPCR, and immunohistochemistry. Safety was evaluated in healthy mice. RESULTS: UPLC-MS/MS identified multiple BSHX constituents, and bioinformatic analyses suggested involvement of NLRP3-related inflammatory and fibrotic pathways. In CKD mice, BSHX dose-dependently reduced serum creatinine and blood urea nitrogen, attenuated renal injury and interstitial fibrosis, and decreased renal NLRP3, caspase-1, GSDMD, IL-1β, and IL-18 expression. BSHX also suppressed FN, α-SMA, MMP-9, IL-6, TNF-α, and MCP-1. In healthy mice receiving BSHX alone, no significant abnormalities were observed in the evaluated serum biochemical indices of renal or hepatic function. CONCLUSION: BSHX ameliorated renal dysfunction and injury in CKD mice and was associated with suppression of NLRP3 inflammasome-mediated pyroptosis, inflammation, and fibrosis. Under the present experimental conditions, BSHX did not induce detectable abnormalities in the evaluated serum indices of hepatic or renal function.