Curcumin and hemopressin treatment attenuates cholestasis-induced liver fibrosis in rats: role of CB1 receptors

Abstract

Curcumin exerts hepatoprotective effects via poorly defined mechanisms. Recently, some studies suggested that this effect was mediated by antagonizing CB1 receptors in hepatic stellate cells. The current study aimed to investigate whether CB1 antagonist, hemopressin, could potentiate the hepatoprotective effect of curcumin, in comparison with silymarin in bile duct-ligated (BDL) rats. Curcumin and hemopressin each alone and in combination ameliorated biochemical and structural fibrotic injury, and downregulated cyclooxygenase-2 (COX-2) and both mRNA and protein levels of nuclear factor kappa B (NF-κB) in fibrotic liver. In contrast to the previous studies, curcumin alone did not affect the gene expression of cannabinoid receptors. However, the combination of hemopressin and curcumin reduced the expression of CB1 in fibrotic liver. Surprisingly, silymarin upregulated CB2 receptors and downregulated CB1 at mRNA level more than all the administered drugs. Both curcumin and hemopressin each alone decreased lipid peroxidation product, malondialdehyde (MDA), while the combination increased the reduced glutathione content. All the administered drugs increased the hepatic antiapoptotic marker, Bcl2. Our study suggests that hemopressin potentiates the hepatoprotective effect of curcumin on fibrotic liver. We identified a new mechanism of the hepatoprotective effect of silymarin via modulation of cannabinoid receptors in fibrotic liver.

Senna singueana: Antioxidant, Hepatoprotective, Antiapoptotic Properties and Phytochemical Profiling of a Methanol Bark Extract

“…On the other hand, the low dose level of the extract (100 mg/kg) showed stronger positive enhancement of Bcl-2 than controls and silymarin ( Figure 7 ). These results were similar to those previously reported [ 41 , 42 ]. To sum up, the low dose level of the extract (100 mg/kg) exerted a remarkable hepatoprotective activity against d -GalN induced hepatic injury and this might be attributed its antioxidant and antiapoptotic effects.…”

Curcumin attenuates hepatic fibrosis and insulin resistance induced by bile duct ligation in rats

“…Curcumin (diferuloylmethane) is a biologically active polyphenol derived from turmeric plant. It has beneficial properties such as anti-inflammatory, anti-diabetic, liver-protective and anti-fibrosis activity ( 20 ) . The effects of curcumin on the prevention of hepatic fibrogenesis have been confirmed ( 21 ) .…”

“…Curcumin (diferuloylmethane), a biologically active polyphenolic component found in Curcuma longa plant, has for centuries been used as a medicinal plant in different countries ( 20 ) . There are many reports of its anti-inflammatory, anti-diabetic, liver-protective and anti-fibrosis activity ( 6 ) .…”

Hepatic stellate cells as key target in liver fibrosis

“…A selective CB 2 agonist, JWH-133, reduces fibrosis by inducing HSC quiescence/apoptosis and reducing IL-17 production by Th17 cells [166, 170]. Nutritional products such as curcumin (diferuloylmethane), a bioactive polyphenolic ingredient of turmeric, may have potential to inhibit CB1 as well as virtually all cellular pathways involved in HSC activation [171, 172]. Antagonism of a serotonin receptor, 5-hydroxytryptamine 2B receptor (5-HT2B), on HSCs attenuates fibrosis and enhances hepatic regeneration [173].…”