Curcumin prevents alcohol-induced liver disease in rats by inhibiting the expression of NF-κB-dependent genes

Abstract

Induction of NF-kappaB-mediated gene expression has been implicated in the pathogenesis of alcoholic liver disease (ALD). Curcumin, a phenolic antioxidant, inhibits the activation of NF-kappaB. We determined whether treatment with curcumin would prevent experimental ALD and elucidated the underlying mechanism. Four groups of rats (6 rats/group) were treated by intragastric infusion for 4 wk. One group received fish oil plus ethanol (FE); a second group received fish oil plus dextrose (FD). The third and fourth groups received FE or FD supplemented with 75 mg. kg(-1). day(-1) of curcumin. Liver samples were analyzed for histopathology, lipid peroxidation, NF-kappaB binding, TNF-alpha, IL-12, monocyte chemotactic protein-1, macrophage inflammatory protein-2, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and nitrotyrosine. Rats fed FE developed fatty liver, necrosis, and inflammation, which was accompanied by activation of NF-kappaB and the induction of cytokines, chemokines, COX-2, iNOS, and nitrotyrosine formation. Treatment with curcumin prevented both the pathological and biochemical changes induced by alcohol. Because endotoxin and the Kupffer cell are implicated in the pathogenesis of ALD, we investigated whether curcumin suppressed the stimulatory effects of endotoxin in isolated Kupffer cells. Curcumin blocked endotoxin-mediated activation of NF-kappaB and suppressed the expression of cytokines, chemokines, COX-2, and iNOS in Kupffer cells. Thus curcumin prevents experimental ALD, in part by suppressing induction of NF-kappaB-dependent genes.

Ginseng, the Root of Panax ginseng C.A. Meyer, Protects Ethanol-Induced Gastric Damages in Rat through the Induction of Cytoprotective Heat-Shock Protein 27

“…Mucoprotective agents such as prostaglandin, glutathione, ornoprostil, sucralfate, and misoprostol have been found to exert protective effects on ethanol-induced gastric damages [27]. In addition to these compounds, natural extracts such as green tea extracts, wogonin, and curcumin showed a potential protective effect against alcoholic diseases [28][29][30]. Our present findings suggest that ginseng, the root of Panax ginseng C.A.…”

Effect of curcumin on visfatin and zinc-α2-glycoprotein in a rat model of non-alcoholic fatty liver disease

“…Curcumin is the main active ingredient in turmeric 9 , and research has shown that it has some therapeutic effect on NAFLD 10,11 . However, the specific mechanism is unclear.…”

Detection of curcumin and its metabolites in hepatic tissue and portal blood of patients following oral administration

“…This pharmacokinetic feature of curcumin, which has been observed across several species, is the result of poor absorption and avid metabolic conjugation and reduction Sharma et al, submitted for publication). Despite the evidence that curcumin is poorly available following oral administration, there are reports that curcumin at 50 -200 mg kg À1 doses exerts biological activity on sites distant from the locus of absorption in rodents, such as breast (Inano and Onoda, 2002), prostate (Frank et al, 2003), lung (Menon et al, 1995) and especially the liver (Busquets et al, 2001;Park et al, 2001;Nanji et al, 2003). Studies on gall bladder contractility following oral curcumin in humans suggest that curcumin may exert biological actions at doses of 20 mg (Rasyid & Lelo 1999;Rasyid et al, 2002).…”