Studies On Selective Regulation And Mechanism Of Chlorogenic Acid On Caffeic Acid Prooxidant Activity

Chlorogenic acid(CGA)and caffeic acid(CA)are common phenolic acids in tea and coffee,and CA has been listed as a Class 2b carcinogen by the International Agency for Research on Cancer(IARC).The harmfulness of CA is associated with its prooxidative activity,although it appears safe to drink tea and coffee within the normal range of intake,possibly as a result of interactions with multiple polyphenols.In this thesis,the differences in pro-oxidation activity of plant polyphenols CGA and CA in the plants represented by tea and coffee and the selective regulation of CGA on the pro-oxidation activity of CA were studied for the first time.Secondly,the effect of CGA isomers on the pro-oxidation activity of CA were compared.In this thesis,through scientific research,models were established for polyphenol autoxidation,hydrogen peroxide generation in vitro,polyphenols-induced quinone protein formation,copper ion-mediated polyphenol oxidation,hydroxyl free radical generation in vitro,and copper ion/polyphenols-induced DNA damage.In the process of the study,the in vitro chemical level of CGA and its isomers were compared with CA in promoting oxidation activity and interaction.The present study mainly reached the following conclusions:(1)Compared with CA,CGA has very weak pro-oxidation activity mediated by autoxidation,and almost no hydrogen peroxide and quinone protein are produced.However,CGA can cooperate with CA dose-dependent to produce hydrogen peroxide,quinone protein,consume protein sulfhydryl group and inhibit protease activity.(2)At the level of pro-oxidation activity mediated by copper ions,the activity of CGA is significantly lower than that of CA.Specifically,CA can significantly reduce Cu(Ⅱ)to Cu(I)in a dose-and time-dependent way,and generate a large number of hydroxyl radicals to induce oxidative damage of DNA,while CGA has no significant effect on the above level.However,CGA can inhibit the reduction of Cu(Ⅱ)by CA and the generation of hydroxyl radicals,and finally reduce the oxidative damage of DNA.(3)Both autoxidation mediated and copper ion-mediated pro-oxidation activities of CGA and the five isomers were weaker than those of CA,and had a selective regulatory effect on CA.In summary,the present study showed that,compared with CA or other polyphenols with strong prooxidation activity,CGA exhibits lower non-copper dependent or dependent prooxidation activity.Furthermore,in autoxidation,CGA promotes the beneficial effects of CA,i.e.the production of quinone and moderate amounts of hydrogen peroxide,thus stimulating endogenous antioxidant systems.On the other hand,CGA inhibits CA oxidation and consequent DNA damage by inhibiting the reduction of Cu(Ⅱ)to Cu(I).CGA can be regarded as an indispensable partner of polyphenols in tea or coffee,as CGA not only reduces the potentially carcinogenic activity of CA,but also increases the autoxidation of CA to a level conducive to disease prevention.