Department of Surgery, University of Texas Medical Branch, Galveston, Texas, 77555, USA.
Department of Anatomy, College of Basic Medicine, Zhengzhou University, Zhengzhou 450066, China.
Biomed Res Int. 2018 Dec 30;2018:6137420. doi: 10.1155/2018/6137420. eCollection 2018.
Hepatic stellate cells (HSCs) play an important role in hepatic fibrogenesis and inflammatory modulation. Endotoxin is dramatically increased in portal venous blood after serious injury and can contribute to liver damage. However, the mechanism underlying endotoxin's effects on HSCs remains largely unknown. Oridonin is a bioactive diterpenoid isolated from that exhibits anti-inflammatory properties in different tissues. In the present study, we determined the effects of oridonin on endotoxin-induced inflammatory response and signaling pathways The production of proinflammatory cytokines in activated human HSCs line LX-2 was measured by ELISA and Western blots. Immunofluorescence and nuclear fractionation assay were used to determine NF-B activity. Oridonin treatment significantly inhibited LPS-induced proinflammatory cytokines IL-1, IL-6, and MCP-1 production as well as cell adhesion molecules ICAM-1 and VCAM-1. Additionally, oridonin blocked LPS-induced NF-B p65 nuclear translocation and DNA binding activity. Oridonin prevented LPS-stimulated NF-B regulator IKK/ and IB phosphorylation and IB degradation. Combined treatment of oridonin and an Hsp70 substrate binding inhibitor synergistically suppressed LPS-stimulated proinflammatory cytokines and NF-B pathway activation. Therefore, oridonin inhibits LPS-stimulated proinflammatory mediators through IKK/IB/NF-B pathway. Oridonin could be a promising agent for a hepatic anti-inflammatory.
肝星状细胞（HSCs）在肝纤维化和炎症调节中发挥重要作用。严重损伤后门静脉血液中的内毒素显著增加，并可能导致肝损伤。然而，内毒素对 HSCs 的作用机制在很大程度上尚不清楚。冬凌草甲素是一种从 中分离得到的生物活性二萜，在不同组织中具有抗炎作用。在本研究中，我们确定了冬凌草甲素对脂多糖诱导的炎症反应和信号通路的影响。通过 ELISA 和 Western blot 测定激活的人 HSCs 系 LX-2 中促炎细胞因子的产生。免疫荧光和核分馏测定用于测定 NF-B 活性。冬凌草甲素处理显著抑制 LPS 诱导的促炎细胞因子 IL-1、IL-6 和 MCP-1 的产生以及细胞黏附分子 ICAM-1 和 VCAM-1。此外，冬凌草甲素阻断了 LPS 诱导的 NF-B p65 核易位和 DNA 结合活性。冬凌草甲素阻止了 LPS 刺激的 NF-B 调节因子 IKK/和 IB 的磷酸化和 IB 的降解。冬凌草甲素与 Hsp70 底物结合抑制剂联合处理协同抑制 LPS 刺激的促炎细胞因子和 NF-B 通路激活。因此，冬凌草甲素通过 IKK/IB/NF-B 通路抑制 LPS 刺激的促炎介质。冬凌草甲素可能是一种有前途的肝脏抗炎剂。
