Shizhifang ameliorates pyroptosis of renal tubular epithelial cells in hyperuricemia through inhibiting NLRP3 inflammasome

作者：Jiabao Zhou, Chuanxu Wang, Xuming Zhang, Zhiyuan Wu, Yansheng Wu, Dong‐Dong Li, Jiandong Gao · 发表于：Journal of Ethnopharmacology · 年份：2023 · DOI：10.1016/j.jep.2023.116777 · 被引用次数：28 · 研究领域：Inflammasome and immune disorders、Gout, Hyperuricemia, Uric Acid、Nephrotoxicity and Medicinal Plants

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese Medicine (TCM) Compound Shizhifang (SZF), consisting of the seeds of four Chinese herbs, has been used in Shanghai Shuguang Hospital in China for more than 20 years and has proven its clinical safety and efficacy in lowering uric acid and protecting kidney function. AIM OF THE STUDY: Hyperuricemia (HUA)-induced pyroptosis of renal tubular epithelial cells serves as a significant cause of tubular damage. SZF proves to be effective in alleviating renal tubular injury and inflammation infiltration of HUA. However, the inhibiting effect of SZF on pyroptosis in HUA still remains elusive. This study aims to verify whether SZF could ameliorate pyroptosis in tubular cells induced by uric acid (UA). MATERIALS AND METHODS: Quality control analysis and chemical and metabolic identification for SZF and SZF drug serum were performed by using UPLC-Q-TOF-MS. In vitro, human renal tubular epithelial cells (HK-2) stimulated by UA were treated with SZF or NLRP3 inhibitor (MCC950). HUA mouse models were induced by intraperitoneal injection of potassium oxonate (PO). Mice were treated with SZF, allopurinol or MCC950. We focused on evaluated the effect of SZF on the NLRP3/Caspase-1/GSDMD pathway, renal function, pathologic structure and inflammation. RESULTS: SZF significantly restrained the activation of the NLRP3/Caspase-1/GSDMD pathway in vitro and in vivo induced by UA. SZF was better than allopurinol and MCC950 in reducing pro-inflammatory ...