Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Dalian 116044, Liaoning Province, China.
Eur J Pharm Sci. 2012 Jan 23;45(1-2):190-4. doi: 10.1016/j.ejps.2011.11.002. Epub 2011 Nov 13.
To investigate the inhibitory effects of ursolic acid (UA) on the expression of C-reactive protein (CRP) induced by IL-6 in HepG2 cells and the protective effects on the CRP-induced injury to human umbilical vein endothelial cells (HUVECs).
HepG2 cells were treated with IL-6 or IL-6 and different concentrations of UA for 48 h, then the cells were collected. The total protein and RNA of the cells were extracted for western blotting and RT-PCR methods to detect CRP protein and mRNA expression. HUVECs were treated with CRP or CRP and different concentrations of UA for 24h. Cell proliferation in each group was assayed by MTT. Cells were collected for western blotting and RT-PCR methods to detect VCAM-1, LOX-1 protein or mRNA expression.
IL-6 can significantly increase CRP protein and mRNA expression in HepG2 cells, and this effect of IL-6 can be decreased by UA (6.25, 12.5, 25 μmol/L) markedly in a dose-dependent manner. UA can inhibit CRP-induced proliferation of HUVECs. CRP can obviously increase LOX-1/VCAM-1 expression in HUVECs, both on mRNA and protein levels and the effect of CRP can be inhibited by UA (5, 10, 20 μmol/L) in a dose-dependent manner.
UA can reduce the over expression of CRP in HepG2 cells induced by IL-6 and inhibit the increased expression of VCAM-1 and LOX-1 in HUVECs caused by CRP. Our research suggests that UA can reduce CRP levels in plasma and prevent inflammatory cytokines from injuring endothelial cells by inhibiting the hepatic synthesis of CRP. So UA may have positive significance for prevention and treatment of atherosclerosis and other cardiovascular diseases.
探讨熊果酸（UA）对 IL-6 诱导 HepG2 细胞 C 反应蛋白（CRP）表达的抑制作用及其对 CRP 诱导人脐静脉内皮细胞（HUVEC）损伤的保护作用。
用 IL-6 或 IL-6 联合不同浓度 UA 处理 HepG2 细胞 48 h，收集细胞，提取细胞总蛋白和 RNA，采用 Western blot 和 RT-PCR 法检测 CRP 蛋白和 mRNA 表达。用 CRP 或 CRP 联合不同浓度 UA 处理 HUVEC 24 h，MTT 法检测各组细胞增殖情况，Western blot 和 RT-PCR 法检测 VCAM-1、LOX-1 蛋白和 mRNA 表达。
IL-6 可明显增加 HepG2 细胞 CRP 蛋白和 mRNA 表达，UA（6.25、12.5、25 μmol/L）呈剂量依赖性显著降低 IL-6 的这种作用。UA 抑制 CRP 诱导的 HUVEC 增殖。CRP 可明显增加 HUVECs 中 LOX-1/VCAM-1 的表达，mRNA 和蛋白水平均如此，UA（5、10、20 μmol/L）呈剂量依赖性抑制 CRP 的作用。
UA 可降低 IL-6 诱导的 HepG2 细胞中 CRP 的过度表达，抑制 CRP 引起的 HUVECs 中 VCAM-1 和 LOX-1 表达增加。本研究提示 UA 可通过抑制肝组织 CRP 的合成降低血浆 CRP 水平，防止炎症细胞因子损伤内皮细胞，对动脉粥样硬化等心血管疾病的防治可能具有积极意义。
