(a)Liver and Immunology Research Center, Daejeon Oriental Hospital of Daejeon University, 22-5 Daeheung-dong, Jung-gu, Daejeon 301-724, Republic of Korea; (b)NAR Center, Inc., Daejeon Oriental Hospital of Daejeon University, Daejeon 301-724, Republic of Korea.
J Ethnopharmacol. 2013 Dec 12;150(3):892-900. doi: 10.1016/j.jep.2013.09.035. Epub 2013 Oct 1.
The Chunggan extract (CGX) is a traditional herbal formula prescribed for patients suffering from various liver diseases, including alcoholic liver disease, in which the mechanism of CGX action remains unclear. This study aimed to investigate the anti-hepatic fibrosis effects of CGX and its underlying mechanisms in alcohol-induced rat livers.
To elucidate the mechanism of action of CGX, we evaluated gene expression profiles in the livers of rats treated with 30% alcohol and anti-fibrotic doses of CGX of 100 and 200 mg/kg/day at 1 day, and 2 and 4 weeks using microarrays. The mRNA and protein expression levels of vascular endothelial growth factor (VEGF), one of the candidate genes selected in this study, in alcohol-induced rat livers were measured by real-time PCR and enzyme-linked immunosorbent assays, respectively.
We identified 4128 genes as differentially expressed by at least twofold between alcohol-only- and alcohol-CGX-fed rats at various doses and time points, compared to naïve control animals. Twenty-three of these genes were associated with liver fibrosis and oxidative stress based on the GeneCards database, resulting in p<0.05 by ANOVA between the alcohol-only and alcohol-CGX groups. Especially, Vegf was decreased in CGX 200 mg/kg/day-fed rat livers at all time points evaluated, and mRNA and protein levels at the 4-week time point were validated.
These gene expression profiles provide a better understanding of the mechanisms underlying the anti-fibrotic effects of CGX. Suppression of VEGF may play a critical role in anti-fibrotic action of CGX in alcoholic liver injury.
忠肝提取物(CGX)是一种传统的草药配方,用于治疗各种肝病患者,包括酒精性肝病,但其作用机制尚不清楚。本研究旨在探讨 CGX 在酒精诱导的大鼠肝脏中的抗肝纤维化作用及其机制。
为了阐明 CGX 的作用机制,我们使用微阵列评估了用 30%酒精和抗纤维化剂量的 100 和 200mg/kg/天的 CGX 治疗 1 天、2 周和 4 周的大鼠肝脏中的基因表达谱。通过实时 PCR 和酶联免疫吸附试验分别测量了酒精诱导的大鼠肝脏中血管内皮生长因子(VEGF)的 mRNA 和蛋白表达水平,VEGF 是本研究中选择的候选基因之一。
与正常对照组相比,我们在不同剂量和时间点的酒精组和酒精-CGX 组之间发现了至少两倍差异表达的 4128 个基因。根据 GeneCards 数据库,这些基因中有 23 个与肝纤维化和氧化应激有关,在酒精组和酒精-CGX 组之间通过 ANOVA 分析达到 p<0.05。特别是,在所有评估的时间点,CGX 200mg/kg/天组的 Vegf 均降低,并且在 4 周时间点验证了 mRNA 和蛋白水平。
这些基因表达谱提供了对 CGX 抗纤维化作用机制的更好理解。VEGF 的抑制可能在 CGX 抗酒精性肝损伤的抗纤维化作用中发挥关键作用。