Studies On The Hepatoprotective Effects Of AP And The Possible Mechanisms

There are plenty of studies reported that apple polyphenols（AP）,which were extracted from apples,had strong antioxidant activity and various pharmacological functions including antiallergic activity,anti-ulcerative and anti-caries activities.AP have been used as food additive and nutritional supplement.Liver disease is considered to be a serious health problem,as the liver is an important organ for the transformation and detoxification of endogenous and exogenous harmful substances.It is, therefore,necessary to discover some potential drugs with high efficacy and more safety remedies for the treatment of liver disease.The study of natural product derived from food as potential hepatoprotective agent will have great application value and wide study prospect.So, in the present study,the hepatoprotective effects of AP were evaluated against CCl₄,D-GalN, alcohol and cisplatin（CP）-induced liver damage in mice as well as the possible mechanisms involved were investigated.1.Acute toxicity tests showed that AP was low-toxicity orally up to 5000 mg/kg and LD₅₀ was 339.78 mg/kg by i.p.in mice.2.AP exhibited strong antioxidant effects on the increase of LPO induced by FeSO₄-L-Cys in rat liver microsomes and DPPH free radical scavenging activity in vitro.3.Pretreatment with AP（200,400,800 mg/kg,i.g.）for 7 days prevented the increase of liver ratio,serum ALT and AST activities in mice injuried by CCl₄ These results were in accordance with histopathological examinations.Moreover,AP（200,400 mg/kg,i.g.）decreased the MDA formation and ameliorated SOD activity,and AP（800 mg/kg,i.g.）increased GSH level in the liver of mice injuried by CCl₄ Furthermore,AP enhanced Ca²⁺-ATPase activity, improved DNA damage by comet assay,and prevented the decrease of mitochondrial membrane potential in hepatic homogenate in CCl₄ injuried mice.4.Pretreatment with AP（400,800 mg/kg,i.g.）for 7 days prevented the increase of serum ALT and AP（800 mg/kg,i.g.）prevented the increase of AST in mice injuried by D-GaiN These results were in accordance with histopathological examinations.Moreover,AP（400,800 mg/kg, i.g.）decreased the MDA formation and ameliorated SOD activity,and AP（800 mg/kg,i.g.） increased GSH level in the liver of mice injuried by D-GalN5.Pretreatment with AP（200,400,800 mg/kg,i.g.）for 7 days prevented the increase of serum ALT and AP（400,800 mg/kg,i.g.）prevented the increase of AST in mice injuried by alcohol.These results were in accordance with histopathological examinations.Moreover,AP （400,800 mg/kg,i.g.）decreased the MDA formation and ameliorated SOD activity,and AP （200,400,800 mg/kg,i.g.）increased GSH level in the liver of mice injuried by alcohol.6.Pretreatment with AP（800 mg/kg,i.g.）for 7 days prevented the increase of serum ALT in mice injuried by CP.AP improved histopathological change in liver of mice injuried by CP. Moreover,AP（800 mg/kg,i.g.）decreased the MDA formation and ameliorated SOD activity and GSH level in the liver of mice injuried by CP7.AP（400,800 mg/kg,i.g.）stimulated liver regeneration in mice excised partial liver and promoted the secretion of bile.In conclusion,AP had hepatoprotective effects with low toxicity and the mechanisms underlying its protective effects may be related to the strong free radical scavenging activity, inhibition of lipid peroxidation,enhancement of antioxidant status,promoting repairment of injuried hepatocytes and protection on the functions of liver cell membrane and mitochondria.This paper provided experimental basis and useful reference for making more exploitation on AP as an optional preventive and therapeutic drug against chemical liver injury.Further study on the molecular mechanisms underlying the hepatoprotective effects of AP is essential.