Total glucosides of paeony decreases apoptosis of hepatocytes and inhibits maturation of dendritic cells in autoimmune hepatitis
Total glucosides of paeony decreases apoptosis of hepatocytes and inhibits maturation of dendritic cells in autoimmune hepatitis
复制标题
白芍总苷减少自身免疫性肝炎肝细胞凋亡并抑制树突状细胞成熟
DOI：
10.1016/j.biopha.2020.109911
复制
发表时间：
2020-04-01
影响因子：
7.5
通讯作者：
Yang, Li
中科院分区：
文献类型：
--
作者：
Shen, Mengyi;Men, Ruoting;Yang, Li
白芍总苷（Total Glucosides of Paeony，TGP）是从白芍中提取的活性成分，具有抗炎和免疫调节作用，广泛用于治疗类风湿性关节炎等自身免疫性疾病。然而，TGP在自身免疫性肝炎（AIH）中的作用仍不清楚。本研究旨在探讨白芍总苷对自身免疫性肝病（AILD）和刀豆蛋白A（Con A）诱导的实验性自身免疫性肝炎（EAH）的影响。AILD患者生化指标的变化表明，TGP治疗对肝功能有明显的保护作用，表现为血清丙氨酸转氨酶、天冬氨酸转氨酶、γ-谷氨酰转肽酶和总胆红素水平下降。在EAH小鼠中，我们发现TGP预处理降低了血清肝酶水平、组织病理学损伤和肝细胞凋亡。重要的是，流式细胞术分析表明，TGP预处理减少了成熟树突状细胞在肝脏中的浸润。在体外实验中，TGP预处理可改善Con A诱导的肝细胞线粒体膜电位下降、活性氧增加和凋亡增加。此外，在此过程中，Box，Cleaved Caspase-3和细胞质细胞色素C的水平下降，而Bcl-2和线粒体细胞色素C的水平上升。因此，白芍总苷可能通过线粒体凋亡途径减少肝细胞凋亡。此外，TGP还抑制了骨髓树突状细胞的成熟。总之，TGP治疗通过调节肝细胞凋亡和DC成熟来改善AIH。TGP是一种潜在的治疗AIH的药物。
Total glucosides of paeony (TGP), an active mixture extracted from paeony root, has anti-inflammatory and immunoregulatory effects and is widely used for the treatment of autoimmune diseases such as rheumatoid arthritis. However, the role of TGP in autoimmune hepatitis (AIH) is still unknown. In this study, we aimed to investigate the effect of TGP in autoimmune liver disease (AILD) patients and in concanavalin A (Con A)-induced experimental autoimmune hepatitis (EAH). Changes in biochemical parameters of AILD patients showed that treatment with TGP exerts significant protective effects on liver function, as reflected by decreased levels of serum alanine transaminase, aspartate transaminase, gamma-glutamyl transpeptidase and total bilirubin. In EAH mice, we found that pretreatment with TGP reduced the levels of serum liver enzyme levels, histopathological damage and hepatocyte apoptosis. Importantly, flow cytometry analysis showed that pretreatment with TGP reduced the infiltration of mature dendritic cells in the liver. In vitro, TGP pretreatment ameliorated the Con A-induced mitochondrial membrane potential decline, reactive oxygen species increase, and apoptosis increase in hepatocytes. In addition, the levels of Box, Cleaved Caspase-3 and cytoplasmic Cytochrome C decreased during this process, whereas those of Bcl-2 and mitochondrial Cytochrome C increased. Therefore, TGP might decrease hepatocyte apoptosis through the mitochondrial apoptotic pathway. Moreover, the maturation of bone marrow dendritic cells was also inhibited by TGP treatment. In conclusion, TGP treatment ameliorates AIH by regulating hepatocyte apoptosis and DC maturation. TGP is a potential compound for AIH treatment.