Yan Fenglian, Li Wenbo, Sun Xueyang, Wang Lin, Liu Zhihong, Zhong Zhaoming, Guo Zhengran, Liu Ziyu, Gao Min, Zhang Junfeng, Wang Changying, Dong Guanjun, Li Chunxia, Chen Shang, Xiong Huabao, Zhang Hui
Institute of Immunology and Molecular Medicine, Jining Medical University, Jining, Shandong, China.
Jining Key Laboratory of Immunology, Jining Medical University, Jining, Shandong, China.
Inflammation. 2024 Nov 26. doi: 10.1007/s10753-024-02189-x.
Sappanone A (SAP), a high-isoflavone compound derived from the traditional Chinese medicine Sumu, exhibits various pharmacological activities, including anti-inflammatory and anti-oxidant effects. However, its protective effects on the liver have rarely been reported. The aim of this study was to investigate the effects of SAP on immune-mediated liver injury induced by concanavalin A (Con A) in mice and to explore the underlying molecular mechanisms. Mice were administered SAP intraperitoneally (50 mg/kg body weight). Three hours later, Con A (18 mg/kg) was injected via the tail vein to induce liver damage. Livers and blood were collected 12 h after Con A challenge. Liver cell apoptosis, oxidative stress, and M1 macrophage activation in vivo were investigated. Bone marrow-derived macrophages were used to confirm the effects of SAP on M1 polarization in vitro. The results indicated that SAP decreased transaminase levels, inhibited apoptosis, and improved oxidative stress in mouse livers. Furthermore, SAP significantly reduced the proportion of macrophages, inhibited the expression of CD86, and downregulated the expression of M1 macrophage-related inflammatory cytokines. Moreover, SAP-treated macrophages alleviated liver damage caused by Con A compared to non-SAP-treated macrophages. Mechanistically, SAP inhibited the phosphorylation of key molecules in the MAPK and NF-κB signaling pathways in macrophages, resulting in an inhibitory effect on M1 macrophage activation. Taken together, SAP alleviates immune-mediated liver injury induced by Con A by suppressing M1 macrophage polarization, which is partially associated with NF-κB and MAPK signaling pathways.
苏木诺酮A（SAP）是一种从传统中药苏木中提取的高异黄酮化合物，具有多种药理活性，包括抗炎和抗氧化作用。然而，其对肝脏的保护作用鲜有报道。本研究旨在探讨SAP对刀豆蛋白A（Con A）诱导的小鼠免疫介导性肝损伤的影响，并探讨其潜在的分子机制。小鼠腹腔注射SAP（50 mg/kg体重）。3小时后，通过尾静脉注射Con A（18 mg/kg）诱导肝损伤。Con A攻击12小时后收集肝脏和血液。研究体内肝细胞凋亡、氧化应激和M1巨噬细胞活化情况。采用骨髓来源的巨噬细胞在体外证实SAP对M1极化的影响。结果表明，SAP降低了小鼠肝脏中的转氨酶水平，抑制了细胞凋亡，并改善了氧化应激。此外，SAP显著降低了巨噬细胞比例，抑制了CD86的表达，并下调了M1巨噬细胞相关炎性细胞因子的表达。而且，与未用SAP处理的巨噬细胞相比，用SAP处理的巨噬细胞减轻了Con A引起的肝损伤。机制上，SAP抑制了巨噬细胞中MAPK和NF-κB信号通路关键分子的磷酸化，从而对M1巨噬细胞活化产生抑制作用。综上所述，SAP通过抑制M1巨噬细胞极化减轻Con A诱导的免疫介导性肝损伤，这部分与NF-κB和MAPK信号通路有关。
