ABSTRACT
Acute hepatic inflammation is regarded as a hallmark of early stage fibrosis, which can progress to extensive fibrosis and cirrhosis. Sinapic acid is a phenylpropanoid compound that is abundant in cereals, nuts, oil seeds, and berries and has been reported to exhibit a wide range of pharmacological properties. In this study, we investigated the anti-inflammatory effect of sinapic acid in carbon tetrachloride (CCl4)-induced acute hepatic injury in rats. Sinapic acid was administered orally (10 or 20 mg/kg) to rats at 30 min and 16 h before CCl4 intoxication. Sinapic acid treatment of rats reduced CCl4-induced abnormalities in liver histology, serum alanine transaminase and aspartate transaminase activities, and liver malondialdehyde levels. In addition, sinapic acid treatment significantly attenuated the CCl4-induced production of inflammatory mediators, including tumor necrosis factor-alpha and interleukin-1ß mRNA levels, and increased the expression of nuclear factor-kappa B (NF-κB p65). Sinapic acid exhibited strong free radical scavenging activity in vitro. Thus, sinapic acid protected the rat liver from CCl4-induced inflammation, most likely by acting as a free radical scavenger and modulator of NF-κB p65 activation and proinflammatory cytokine expression. Sinapic acid may thus have potential as a therapeutic agent for suppressing hepatic inflammation.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Carbon Tetrachloride/toxicity , Chemical and Drug Induced Liver Injury/prevention & control , Coumaric Acids/therapeutic use , Free Radical Scavengers/therapeutic use , Acute Disease , Animals , Anti-Inflammatory Agents/administration & dosage , Biphenyl Compounds/chemistry , Blotting, Western , Body Weight/drug effects , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/immunology , Chemical and Drug Induced Liver Injury/pathology , Coumaric Acids/administration & dosage , Disease Models, Animal , Free Radical Scavengers/administration & dosage , Interleukin-1beta/antagonists & inhibitors , Interleukin-1beta/biosynthesis , Interleukin-1beta/immunology , Lipid Peroxidation/drug effects , Liver/drug effects , Liver/enzymology , Liver/immunology , Liver/pathology , Liver Function Tests , Male , Molecular Structure , Organ Size/drug effects , Picrates/chemistry , Rats , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction , Transcription Factor RelA/antagonists & inhibitors , Transcription Factor RelA/biosynthesis , Transcription Factor RelA/immunology , Transforming Growth Factor beta1/antagonists & inhibitors , Transforming Growth Factor beta1/biosynthesis , Transforming Growth Factor beta1/immunologyABSTRACT
Sinapic acid is a member of the phenylpropanoid family and is abundant in cereals, nuts, oil seeds, and berries. It exhibits a wide range of pharmacological properties. In this study, we investigated the hepatoprotective and antifibrotic effects of sinapic acid on dimethylnitrosamine (DMN)-induced chronic liver injury in rats. Sinapic acid remarkably prevented DMN-induced loss of body weight. This was accompanied by a significant increase in levels of serum alanine transaminase, aspartate transaminase, and liver malondialdehyde content. Furthermore, sinapic acid reduced hepatic hydroxyproline content, which correlated with a reduction in the expression of type I collagen mRNA and histological analysis of collagen in liver tissue. Additionally, the expression of hepatic fibrosis-related factors such as α-smooth muscle actin and transforming growth factor-ß1 (TGF-ß1), were reduced in rats treated with sinapic acid. Sinapic acid exhibited strong scavenging activity. In conclusion, we find that sinapic acid exhibits hepatoprotective and antifibrotic effects against DMN-induced liver injury, most likely due to its antioxidant activities of scavenging radicals, its capacity to suppress TGF-ß1 and its ability to attenuate activation of hepatic stellate cells. This suggests that sinapic acid is a potentially useful agent for the protection against liver fibrosis and cirrhosis.
