Department of Animal Science and Technology, National Taiwan University, Taiwan.
J Nutr Biochem. 2012 Oct;23(10):1352-66. doi: 10.1016/j.jnutbio.2011.08.004. Epub 2012 Jan 4.
Inflammation and hepatic stellate cell (HSC) activation are the most crucial steps in the formation of hepatic fibrosis. Hepatocytes damaged by viral or bacterial infection, alcohol or toxic chemicals initiate an inflammatory response that activates collagen production by HSCs. Recent studies indicate curcumin has liver-protective effects due to its anti-inflammatory, antioxidant and anticancer activities; however, the mechanisms are not well understood. In this study, we show that curcumin protected against hepatic fibrosis in BALB/c mice in vivo by inhibiting HSC activation, inflammatory responses and inducing apoptosis of damaged hepatocytes. Using the thioacetamide (TAA)-induced hepatic fibrosis animal model, we found that curcumin treatment up-regulated P53 protein expression and Bax messenger RNA (mRNA) expression and down-regulated Bcl-2 mRNA expression. Together, these responses increased hepatocyte sensitivity to TAA-induced cytotoxicity and forced the damaged cells to undergo apoptosis. Enhancing the tendency of damaged hepatocytes to undergo apoptosis may be the protective mechanism whereby curcumin suppresses inflammatory responses and hepatic fibrogenesis. These results provide a novel insight into the cause of hepatic fibrosis and the cytoprotective effects curcumin has on hepatic fibrosis suppression.
炎症和肝星状细胞(HSC)激活是肝纤维化形成的最关键步骤。病毒或细菌感染、酒精或有毒化学物质损伤的肝细胞会引发炎症反应,激活 HSC 产生胶原。最近的研究表明,姜黄素具有抗炎、抗氧化和抗癌作用,因此对肝脏具有保护作用;然而,其机制尚不清楚。在这项研究中,我们表明姜黄素通过抑制 HSC 激活、炎症反应和诱导损伤的肝细胞凋亡,在体内保护 BALB/c 小鼠免受肝纤维化。使用硫代乙酰胺(TAA)诱导的肝纤维化动物模型,我们发现姜黄素治疗可上调 P53 蛋白表达和 Bax 信使 RNA(mRNA)表达,并下调 Bcl-2 mRNA 表达。这些反应共同增加了肝细胞对 TAA 诱导的细胞毒性的敏感性,并迫使受损细胞发生凋亡。增强受损肝细胞发生凋亡的趋势可能是姜黄素抑制炎症反应和肝纤维化形成的保护机制。这些结果为肝纤维化的原因和姜黄素抑制肝纤维化的细胞保护作用提供了新的见解。