Li Qi, Meng Qian, Niu Ningning, Li Yiqian, Lu Wenye, Wang Tianming, Li Yuanyuan, Ju Wanjun, Ma Yueming, Wu Jiasheng
Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Department of Pharmacology, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
J Ethnopharmacol. 2025 May 12;347:119720. doi: 10.1016/j.jep.2025.119720. Epub 2025 Mar 31.
Neutrophil extracellular traps (NETs) are important driving factors to liver disease. Yinchenzhufu decoction (YCZFD) is a classical traditional herbal medicine used to treat cholestatic liver injury (CLI); however, its effect on NETs in CLI remains unknown.
To elucidate the potential molecular mechanism of YCZFD against CLI through multiple omics techniques.
The protective effects of YCZFD against cholestatic liver injury and fibrosis were investigated in a 3, 5-Diethoxycarbonyl-1, 4-Dihydro-2, 4, 6-Collidine (DDC) induced cholestatic mouse model. Its effects on blood biochemical indicators, liver tissue morphology, neutrophil infiltration, and fibrosis in cholestatic mice were determined. Then RNA sequencing, quantitative proteomics, and molecular biology were used to analyze the mechanism of YCZFD against CLI.
Treatment different doses of YCZFD significantly ameliorated neutrophil infiltration, alleviating CLI in cholestatic mice. RNA sequencing showed that neutrophil recruitment genes, such as CXCL5 and CXCR2, were upregulated in the liver tissues of cholestatic mice, but YCZFD treatment decreased this expression. Additionally, quantitative proteomics revealed that liver myeloperoxidase and S100A9 expression, key marker proteins of NETs, was significantly increased in cholestatic mice and decreased by YCZFD. Similarly, molecular biology confirmed that YCZFD reduced NETs proteins expression and ameliorated NETs formation in the liver of cholestatic mice. As NETs promotes inflammation, further results showed that YCZFD treatment inhibited the NF-κB signaling pathway and collagen formation, alleviating liver inflammation and fibrosis of cholestatic mice.
YCZFD decreases neutrophil recruitment and formation of NETs, in turn alleviating cholestatic liver injury and fibrosis.
中性粒细胞胞外陷阱（NETs）是肝脏疾病的重要驱动因素。茵陈术附汤（YCZFD）是一种用于治疗胆汁淤积性肝损伤（CLI）的经典传统草药；然而，其对CLI中NETs的影响尚不清楚。
通过多组学技术阐明YCZFD抗CLI的潜在分子机制。
在3,5 - 二乙氧基羰基 - 1,4 - 二氢 - 2,4,6 - 可力丁（DDC）诱导的胆汁淤积小鼠模型中研究YCZFD对胆汁淤积性肝损伤和纤维化的保护作用。测定其对胆汁淤积小鼠血液生化指标、肝组织形态、中性粒细胞浸润和纤维化的影响。然后采用RNA测序、定量蛋白质组学和分子生物学方法分析YCZFD抗CLI的机制。
给予不同剂量的YCZFD治疗可显著改善中性粒细胞浸润，减轻胆汁淤积小鼠的CLI。RNA测序显示，胆汁淤积小鼠肝组织中中性粒细胞募集基因如CXCL5和CXCR2上调，但YCZFD治疗可降低这种表达。此外，定量蛋白质组学显示，NETs的关键标志物蛋白肝脏髓过氧化物酶和S100A9表达在胆汁淤积小鼠中显著增加，而YCZFD可使其降低。同样，分子生物学证实YCZFD可降低NETs蛋白表达并改善胆汁淤积小鼠肝脏中NETs的形成。由于NETs促进炎症，进一步结果表明YCZFD治疗可抑制NF - κB信号通路和胶原形成，减轻胆汁淤积小鼠的肝脏炎症和纤维化。
YCZFD可减少中性粒细胞募集和NETs形成，进而减轻胆汁淤积性肝损伤和纤维化。
