International Immunopharmacology ( IF 4.8 ) Pub Date : 2021-03-18 , DOI: 10.1016/j.intimp.2021.107527 Jie Pan 1 , Sanyang Chen 2 , Wenzhi Guo 1 , Shengli Cao 1 , Xiaoyi Shi 1 , Jiakai Zhang 1 , Huapeng Zhang 1 , Shuijun Zhang 1
Liver damage induced by ischemia/reperfusion (I/R) remains a primary issue in liver transplantation and resection. Alpinetin, a novel plant flavonoid derived from Alpinia katsumadai Hayata, is widely used to treat various inflammatory diseases. However, the effects of alpinetin on hepatic I/R injury remain unclear. The present study investigated the protective effects of alpinetin pretreatment on hepatic I/R injury in mice. C57BL/6 mice were subjected to 1 h of partial hepatic ischemia followed by 6 h of reperfusion. Alpinetin (50 mg/kg) was given by intraperitoneal injection 1 h before liver ischemia. The blood and liver tissues were collected to assess biochemical indicators, hepatocyte damage, and levels of proteins related to signaling pathways. Furthermore, a hepatocytes hypoxia/reoxygenation (H/R) model was established for in vitro experiments. In vivo, we observed that alpinetin significantly attenuated the increases in alanine aminotransferase, aspartate transaminase, proinflammatory cytokines, hepatocyte damage, and apoptosis caused by hepatic I/R. Moreover, the hepatic I/R-induced nuclear factor kappa-B (NF-κB)/mitogen-activated protein kinase (MAPK) pathways were suppressed by alpinetin. In vitro, we also observed that alpinetin inhibited the inflammatory response, apoptosis, and activation of the NF-κB/MAPK pathways in hepatocytes after H/R treatment. Our data indicate that alpinetin ameliorated the inflammatory response and apoptosis induced by hepatic I/R injury in mice. The protective effects of alpinetin on hepatic I/R injury may be due to its ability to inhibit the NF-κB/MAPK signaling pathways. These results suggest that alpinetin is a promising potential therapeutic reagent for hepatic I/R injury.
中文翻译:
Alpinetin 通过抑制 NF-κB/MAPK 信号通路保护小鼠肝脏缺血/再灌注损伤
缺血/再灌注(I/R)引起的肝损伤仍然是肝移植和切除中的主要问题。 Alpinetin 是一种从Alpinia katsumadai Hayata 中提取的新型植物黄酮类化合物,广泛用于治疗各种炎症性疾病。然而,阿尔卑斯山素对肝缺血再灌注损伤的影响仍不清楚。本研究探讨了高山素预处理对小鼠肝缺血再灌注损伤的保护作用。 C57BL/6 小鼠经历 1 小时的部分肝缺血,然后再灌注 6 小时。肝缺血前1小时腹腔注射Alpinetin (50 mg/kg)。收集血液和肝组织以评估生化指标、肝细胞损伤以及与信号通路相关的蛋白质水平。此外,建立了肝细胞缺氧/复氧(H/R)模型用于体外实验。在体内,我们观察到 alpinetin 显着减弱了肝脏 I/R 引起的丙氨酸转氨酶、天冬氨酸转氨酶、促炎细胞因子、肝细胞损伤和细胞凋亡的增加。此外,肝缺血再灌注诱导的核因子 kappa-B (NF-κB)/丝裂原激活蛋白激酶 (MAPK) 途径被 alpinetin 抑制。在体外,我们还观察到高山素在H/R处理后抑制肝细胞的炎症反应、细胞凋亡和NF-κB/MAPK通路的激活。我们的数据表明,阿尔卑斯山素可改善小鼠肝缺血再灌注损伤引起的炎症反应和细胞凋亡。 Alpinetin 对肝 I/R 损伤的保护作用可能是由于其抑制 NF-κB/MAPK 信号通路的能力。 这些结果表明高山素是一种有前途的潜在治疗肝缺血再灌注损伤的试剂。