Antioxidant properties of flavonoid derivatives and their hepatoprotective effects on CCl 4 induced acute liver injury in mice.

Excessive accumulation of free radicals in the body can cause liver damage, aging, cancer, stroke, and myocardial infarction. Anastatin B, a skeletal flavonoid, was reported to have antioxidant and hepatoprotective effects. Anastatin B derivatives, compound 1 and 2, were synthesized by our group previously. In this study, their antioxidant activity and hepatoprotective mechanism were studied using chemical evaluation methods, a cellular model of hydrogen peroxide (H 2 O 2 )-induced oxidative damage, and a mouse model of carbon tetrachloride (CCl 4 )-induced liver injury. Results from the chemical evaluation suggested that both compounds had good antioxidant power and radical scavenging ability in vitro . MTT assay showed that both compounds had cytoprotective activity in H 2 O 2 -treated PC12 cells. Moreover, their hepatoprotective activities evaluated using a mouse model of CCl 4 -induced liver injury that compared with the model group, pretreatment with compound 1 and 2 significantly decreased alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), and malondialdehyde (MDA) levels; reduced the liver tissue damage; and increased glutathione content. However, compound 2 was a more effective hepatoprotectant than compound 1 was. Finally, the amount of TNF-α and cytochrome P450 2E1 (CYP2E1) were significantly downregulated in compound 1 and 2 pretreatment groups. Collectively, our findings demonstrate that both compounds have potential antioxidant activity and hepatoprotective effect in vitro and in vivo . Further chemo-biological study and investigation of the compounds' enzymatic targets are ongoing.