Effect of ellagic acid, a plant polyphenol, on fibrotic markers (MMPs and TIMPs) during alcohol-induced hepatotoxicity

Alcoholic fibrosis and its end-stage cirrhosis occur when the rate of matrix synthesis exceeds matrix degradation. Hepatic fibroproliferation is associated with alterations of hepatic tissue inhibitors of matrix metalloproteinase (TIMPs) and matrix metalloproteinases (MMPs/matrixins) expressions. The alteration of hepatic matrixins and TIMPs expression to disease stage and inflammatory activity underlines their potential diagnostic markers in chronic liver disease. Ellagic acid (EA), a natural phenolic compound found in fruits and nuts, has potent antioxidant, anti-inflammatory, and anticancerous properties. The aim of our study was to gain further insight into the effect of EA on fibrotic markers (MMPs and TIMPs) during alcohol-induced tissue injury. To elucidate the effect on the MMPs/TIMPs balance by EA, gelatin zymography, multiwell zymography, succinylated gelatin assay, and ELISA technique (for TIMPs) were carried out. Coadministration of EA with alcohol decreased the expression of MMP-2 and -9 and TIMP-2 in a dose-dependent manner. These results suggest that EA at the dosage of 60 mg/kg body weight effectively decreased the expression pattern of fibrotic markers during alcohol-induced toxicity. Hence, it can be developed as an antifibrotic compound in near future.