Curcumin inhibits collagen synthesis and hepatic stellate cell activation in-vivo and in-vitro

Abstract

We previously demonstrated that curcumin, a well-known antioxidant, inhibits collagen deposition in carbon tetrachloride-induced liver injury in rats. The major effector cells responsibleforcollagensynthesis in the liver are activated hepatic stellate cells. In this study,we investigated the inhibitory effects of curcumin on the collagen synthesis and activation of rat hepatic stellate cells in-vitro, and on hepatic stellate cell activation in-vivo. The effects of curcumin on the production of collagen and smooth muscle alpha-actin proteins and of alpha1(I) collagen mRNA were studied in-vivo and in-vitro. The effect of curcumin on DNA synthesis was also determined in-vitro. In-vivo, treatment with curcumin reduced collagen deposition and smooth muscle alpha-actin-positive areas and lowered mRNA levels of type I collagen in the liver. In-vitro, curcumin at a concentration of 5 microg mL(-1) reduced DNA synthesis, and downregulated smooth muscle alpha-actin and type I collagen expression, and alpha1(I) collagen mRNA expression. We concluded that curcumin inhibits collagen synthesis and hepatic stellate cell activation in-vivo and in-vitro, and thus may prove a valuable anti-fibrogenic agent.

Effect of curcumin on the proliferation and apoptosis of hepatic stellate cells

“…Enhanced HSC apoptosis may reduce the formation of procollagen and increase extracellular matrix degradation, aiding the recovery from hepatic fibrosis. Curcumin not only inhibits HSC proliferation in the S phase and induces apoptosis, but also inhibits the transformation of HSC from a quiescent phenotype to an activated phenotype, and decreases the expression of alpha-smooth muscle actin, a marker of HSC activation (13,14). Curcumin also reduces the secretion of type I collagen in HSC in vitro, and the collagen deposition in the liver of rats with hepatic fibrosis induced by carbon tetrachloride (13,14).…”

“…Curcumin not only inhibits HSC proliferation in the S phase and induces apoptosis, but also inhibits the transformation of HSC from a quiescent phenotype to an activated phenotype, and decreases the expression of alpha-smooth muscle actin, a marker of HSC activation (13,14). Curcumin also reduces the secretion of type I collagen in HSC in vitro, and the collagen deposition in the liver of rats with hepatic fibrosis induced by carbon tetrachloride (13,14). An earlier human study showed no significant side effects in a group of volunteers treated with 8 g curcumin per day for three months (15).…”

Concomitant Oral Ingestion of Germanium-132 and Curcumin Increased Mortality Rate by Aggravating Hepatic Dysfunction in Long-Evans Cinnamon Rats

“…The breeding conditions of rats in the experimental period were: room temperature of 23 ± 1°C, humidity of 60 ± 5%, and 12 hr of the day-and-night cycle (daytime: 8: 30-20:30). Preparation of Ge-132 and Curcumin ---Curcumin (Sigma-Aldrich St. Louis, MO, U.S.A.) was dissolved in corn oil to make an oil emulsion containing 50 mg/ml according to the method of Kang et al 4) Curcumin emulsion was daily administered at up to 100 mg/kg body weight using a disposable feeding syringe (Kenis Ltd., Osaka, Japan). Ge-132 [Orugano Germanium (GeCH 2 CH 2 COOH) 2 O 3 ], Teichu Co., Hiroshima, Japan) was treated by electrostatic induction (1200 volts at 80-85°C) to increase its solubility in water and dissolved in sterile water to make a stock solution of 40 mg/ml.…”

“…3,4) For example, curcumin can effectively suppress diethylnitrosamine-induced liver inflammation and hyperplasia in rats. 5,6) Germanium-132 (2-carboxyethyl germanium sesquioxide, Ge-132) is an organic germanium compound which is known to have immunostimulating effects including induction of interferon-γ through stimulating T-cells, enhancement of natural killer cell activity, and inhibition of tumor growth and its metastasis by stimulation of cytotoxic macrophages.…”

Therapeutic potential of curcumin in non-alcoholic steatohepatitis

“…CUR also inhibits hepatic stellate cell (HSC) activation and type I collagen production (Kang et al 2002;Xu et al 2003). CUR's ability to prevent hyperglycaemia in a mice model of type 2 diabetes (Nishiyama et al 2005), and to inhibit inhibitory kB kinase (IKK; Joe et al 2004) and c-Jun N terminus protein kinase (JNK; Chen & Tan, 1998), which interfere with insulin signal transduction, suggests that it may also ameliorate IR.…”