Hepatoprotective activity of chrysin is mediated through TNF-α in chemically-induced acute liver damage: An in vivo study and molecular modeling

Abstract

Chrysin (5,7-dihydroxyflavone) is a naturally occurring flavonoid present at high levels in honey, propolis and numerous plant extracts. Chrysin is known to have hepatoprotective activity, however, the mechanisms by which it exerts this effect remain unclear. In the present study, the effects of chrysin in carbon tetrachloride (CCl4)-induced acute liver damage were investigated and the results used to infer a possible mechanism behind chrysin's hepatoprotective activity. Prior to an intraperitoneal injection of CCl4 (1 ml/kg) to induce acute liver damage, chrysin (50 mg/kg) was administered orally to mice for 7 days. The positive control group was given 50 mg/kg standardized silymarin, a well-studied hepatoprotective flavonoid. Twenty-four h following CCl4 administration, an increase in the activity levels of serum aspartate-amino-transferase and alanine-amino-transferase was found. This was accompanied by extended centrilobular necrosis, steatosis and an altered hepatocyte ultrastructure. In addition, CCl4-induced acute hepatotoxicity was associated with an increase in hepatic tumor necrosis factor-α (TNF-α) and α-smooth muscle actin (α-SMA) protein expression, which was significantly decreased in the livers of mice pre-treated with chrysin (P<0.001), similar to the results of the silymarin pre-treated group (P<0.001). Treatment with chrysin prior to CCl4 exposure significantly reduced the activity of enzymes used as biochemical markers of poor liver function compared with the group which did not receive pre-treatment (P<0.001). In addition, the results of histopathological and electron microscopy liver examination showed chrysin pre-treatment reduced the effects of CCl4 treatment. Molecular modeling results demonstrated that the hepatoprotective activity of chrysin is mediated through TNF-α, as it reduces soluble TNF-α generation via blocking TNF-α-converting enzyme activity. In conclusion, the results of the present study suggest that inflammatory pathways are activated in CCl4-induced acute liver damage, which are ameliorated by chrysin pre-treatment. This indicates that chrysin is a potent hepatoprotective agent, similarly to silymarin at the same dose, which has the potential to be a viable alternative to conventional hepatoprotective treatments.

The effects of chrysin on lipopolysaccharide‐induced sepsis in rats

“…The obtained results are consistent with previous studies that in LPS-induced septic animals (Kim & Kim, 2002;Wahby, Yacout, Kandeel, & Awad, 2015). Hermenean et al, (2017) reported that CR reduced ALT, AST levels. It was revealed that CR reduced to AST (Harasstani, Tham, & Israf, 2017).…”

Therapeutic Implication of Honey against Chronic Carbon Tetrachloride-Induced Liver Injury via Enhancing Antioxidant Potential and Maintenance of Liver Tissue Architecture

“…Moreover, the mice treated with honey in addition to CCl 4 , had a significantly reduced the level of these enzymes toward the reference range (Figure 1). These results agree with the earlier study as it was reported that serum ALT and AST activity was significantly increased in CCl 4 treated groups as compared to the normal control 10 .…”

Chrysin ameliorates ANTU‐induced pulmonary edema and pulmonary arterial hypertension via modulation of VEGF and eNOs

“…However, administration of chrysin inhibited these ANTU‐induced hepatic aberrations, which were further confirmed by amelioration in serum AST and ALT levels. Results of the present investigation are accordance with findings of a previous researcher depicting the hepatoprotective potential of chrysin via inhibition of AST and ALT levels …”