PT - JOURNAL ARTICLE AU - Yumei Fu AU - Shizhong Zheng AU - Jianguo Lin AU - Jan Ryerse AU - Anping Chen TI - Curcumin Protects the Rat Liver from CCl<sub>4</sub>-Caused Injury and Fibrogenesis by Attenuating Oxidative Stress and Suppressing Inflammation AID - 10.1124/mol.107.039818 DP - 2008 Feb 01 TA - Molecular Pharmacology PG - 399--409 VI - 73 IP - 2 4099 - http://molpharm.aspetjournals.org/content/73/2/399.short 4100 - http://molpharm.aspetjournals.org/content/73/2/399.full SO - Mol Pharmacol2008 Feb 01; 73 AB - We previously demonstrated that curcumin, a polyphenolic antioxidant purified from turmeric, up-regulated peroxisome proliferator-activated receptor (PPAR)-γ gene expression and stimulated its signaling, leading to the inhibition of activation of hepatic stellate cells (HSC) in vitro. The current study evaluates the in vivo role of curcumin in protecting the liver against injury and fibrogenesis caused by carbon tetrachloride (CCl4) in rats and further explores the underlying mechanisms. We hypothesize that curcumin might protect the liver from CCl4-caused injury and fibrogenesis by attenuating oxidative stress, suppressing inflammation, and inhibiting activation of HSC. This report demonstrates that curcumin significantly protects the liver from injury by reducing the activities of serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase, and by improving the histological architecture of the liver. In addition, curcumin attenuates oxidative stress by increasing the content of hepatic glutathione, leading to the reduction in the level of lipid hydroperoxide. Curcumin dramatically suppresses inflammation by reducing levels of inflammatory cytokines, including interferon-γ, tumor necrosis factor-α, and interleukin-6. Furthermore, curcumin inhibits HSC activation by elevating the level of PPARγ and reducing the abundance of platelet-derived growth factor, transforming growth factor-β, their receptors, and type I collagen. This study demonstrates that curcumin protects the rat liver from CCl4-caused injury and fibrogenesis by suppressing hepatic inflammation, attenuating hepatic oxidative stress and inhibiting HSC activation. These results confirm and extend our prior in vitro observations and provide novel insights into the mechanisms of curcumin in the protection of the liver. Our results suggest that curcumin might be a therapeutic antifibrotic agent for the treatment of hepatic fibrosis. The American Society for Pharmacology and Experimental Therapeutics