Potential antifibrotic effect of honokiol in an experimental model of liver fibrosis

Abstract

Liver fibrosis represents a massive global health burden with limited therapeutic options. Therefore, the need for development of novel treatment is such an urge. Honokiol, a natural biphenoilic compound, possesses multiple biological activities, such as antioxidant, anti-inflammatory and anti-cancer. The present study was divided into two parts. The first part aimed at screening the hepatoprotective dose of honokiol where male Sprague-Dawley rats received honokiol once daily for 5 consecutive days at doses of 5, 10 & 20 mg/kg orally followed by a single dose of Con A (20 mg/kg, IV) on the fifith day. Con A induced significant liver damage as proved by the significant elevation in aminotransferases activities with marked histopathological damage. This was almost prevented by pre-treatment with honokiol at dose 10 mg/kg. The selected dose was further used in the second part of the study that designed to assess the potential antifibrotic effect of honokiol in a rat model Con A-induced liver fibrosis as well as to study the possible molecular underlying mechanisms. Male Sprague-Dawley adult rats were treated with either Con A (20 mg/kg, once a week) and/or honokiol (10 mg/kg, five times a week) for four consecutive weeks. Con A induced a significant increase in liver index and serum aminotransferases, while induced a significant decrease in albumin level. Honokiol co-treatment protected against Con A-induced alterations with preservation of normal hepatic architecture. Liver fibrosis induced by Con A was evidenced by increased α-SMA expression and collagen deposition as indicated by Masson’s trichome staining and significant elevation of hydroxyproline content. Honokiol significantly reduced the aforementioned liver fibrosis markers. To elucidate the underlying molecular mechanisms, the effect of honokiol on oxidative stress markers, inflammatory markers and fibrosis markers was assessed. Con A significantly elevated lipid peroxides, while significantly depleted glutathione as well as superoxide dismutase enzyme. In addition, Con A increased NF-κB expression with subsequent downstream of inflammatory cytokines such as TNF-α and INF-γ as well as inflammatory enzymes such as iNOS