Docking and in vivo study role of Kaempferol targeting inflammatory mediators in hepatitis induced by Thoacetamide in Rats.

Hepatitis is one of major serious liver disease that end with decompensated cirrhosis. It caused by many factors as viruses, chemicals, life style and alcohol. Exploring the mechanism of hepatic injury in early stage can manage it and deceased mortality. Kaempferol is one of flavonoids present in many plants that used as folk medicine worldwide. Here, we investigated the mechanism of hepato-protective activity of Kaempferol against thioacetamide (TAA) induced acute inflammation and hepatitis in rats. Six groups of rats were included (each 6 rats) in this study ; Control, TAA intoxicated rats injected single dose of TAA intraperitoneal (300 mg/kg b.w) , TAA + Kaempferol (20 mg/kg treated) and TAA+ kaempefrol (40 mg/kg treated), TAA + Kaempferol (20 mg/kg protected) and TAA+ kaempefrol (40 mg/kg protected) . Serum liver function (ALT, AST, ALP, GGT) , malondialdhyde (MDA) , reduced glutathione (GSH), glutathione peroxidase (GSH-Px), glutathione S- transferase (GSH-T) and inflammatory mediators (NO, IL-6 and TNF-α), glutamate dehydrogenase (GLDH), malate dehydrogenase (MDH), and Paraxonase 1 (PON1)were evaluated. Results obtained showed that, TAA increased of liver enzymes (ALT,AST, ALP, GGT) (p<0.001), MDA, NO, TNFα, IL-6 (p<0.001) levels versus control . In addition, reduced the activities of GSH-Px, GSH-T, GSH level and non significant changes in GLDH and MDH (p<0.001) . Also, an elevation of PON1 (p<0.001) versus control. Kaempferol administration protected against these abnormalities by suppressing production of inflammatory mediator (p<0.001) and stimulate antioxidant activities (p<0.001). In conclusion, it was suggested that, Kaempferol possesses antioxidant and anti-inflammatory effects against hepatitis induced by TAA. The protected effect is more potent than treated. Docking study showed that, Kaempferol exert strong specific binding to inflammatory receptors -8 ATP