Study On The Anti-oxidative Activity Of Anastains A&B And Their Protective Effect On CCl₄-Induced Acute Liver Injury In A Mouse Model

Oxidative stress can cause cell injury and death,which may relate to many diseases such as liver damage,aging,cancer,stroke,myocardial infarction,Alzheimer’s disease,Parkinson’s disease,and so on.Anastatins A&B,a skeletal flavonoid compound that isolated from the desert plant Anastatica hierochuntica,was reported has hepatoprotective activities for the injury of primary rat hepatocyte.Anastatins A&B and its derivatives were synthesized by our group previously.In this study,the anti-oxidative activities of Anastatins A&B and its derivatives were evaluated by using chemical evaluation method,cell oxidative damage model and carbon tetrachloride-induced liver injury mice model.Meanwhile,their hepatoprotective mechanism was also studied.Firstly,several chemical evolution experiments were performed to evaluate the total reducing antioxidant power,ABTS· radical scavenging ability and DPPH· radical scavenging ability of the Anastatins A&B and its derivatives.The results represented that derivative 1-38c had good antioxidant activity in these three test methods.The total r reducing antioxidant powers were 318.13 g/mol,EC50 of ABTS·radical scavenging abilities were 0.08 mM,and EC50 of DPPH·radical scavenging abilities were 0.06 mM.The antioxidant activity was stronger than Vc,comparabled to gallic acid.Secondly,the antioxidant activities of Anastatins A&B and its derivatives were evaluated by PC-12 cells oxidative damage model and L02 cells oxidative damage model.The results represented that derivative 1-38c had good antioxidant activity in two test methods.When PC-12 cells were treated 10 μM of derivative 1-38c,the cell viabilities was increased from 16.80%to 70.59%.When L02 cells were treated 10 μM of derivative 1-38c,the cell viabilities was increased from 39.90%to 78.10%.In two cell oxidative damage model,the antioxidant activity of derivative 1-38c was stronger than gallic acid.Finally,the hepatoprotective activities of derivative 1-38c were evaluated by carbon tetrachloride-induced liver injury in mice.The results showed that:the levels of ALT,AST,and LDH had decreased significantly in derivative 1-38c pretreatment groups,and the GSH content were significantly increased compared with the model group.HE staining results showed that the liver tissue damage were significantly reduced in derivative 1-38c pretreatment groups,compared with the model group.Moreover,the amount of CYP2E1 were significantly down regulated in derivative 1-38c pretreatment groups.Overall,the findings indicated that derivative 1-38c possesses potential antioxidant activity and hepatoprotective activities both in vitro and in vivo.Meanwhile,derivatives 1-38c might exhibits a protective effect on CC14-induced hepatic injury by suppressing the amount of CYP2E1.Further chemo-biological study of derivative 1-38c with regards to its antioxidative and hepatoprotective pathway as well as its enzymatic targets and in vivo investigation are ongoing in this laboratory.