Antioxidant Effects Of Resveratrol And Its Analogues And Hydroxycinnamic Acid Derivatives

Resveratrol (3,5,4'-trans-trihydroxystilbene) is a natural phytoalexin present in grapes and red wine, which possesses a variety of biological activities including antioxidative activity. In order to find more active antioxidants with resveratrol as the lead compound we synthesized resveratrol analogues, i.e., 3,3',4,4'-tetrahydroxy-trans-stillbene(3,3'4,4'-THS), 3,4,4'-trihydroxy-trans-stilbene(3,4,4'-THS). 2,4,4'-trihydroxy-trans-stilbene(2,4,4'-THS). 3,3' -dimethoxy-4,4' -dihydroxy-trans-stilbene(3,3' -DM-4,4' -DHS), 3,4-dihydroxy-trans-stilbene (3,4-DHS), 4.4'-dihydroxy-trans-stilbene (4,4'-DHS), 3,5-dihydroxy-trans-stilbene (3,5-DHS) and 2,4-dihydroxy-trans-stilbene (2,4-DHS). Antioxidative effects of resveratrol and its analogues against free-radical-induced peroxidation of human low density lipoprotein (LDL) were studied. The peroxidation was initiated either by a water-soluble initiator 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH), or by cupric ion (Cu²⁺). The reaction kinetics were monitored either by the uptake of oxygen and the depletion of α-tocopherol (TOH) presented in the native LDL, or by the formation of thiobarbituric acid reactive substances (TBARS). Kinetic analysis of the antioxidation process demonstrates that these trans-stilbene derivatives are effective antioxidants against both AAPH- and Cu²⁺-induced LDL peroxidation with the activity sequence of 3,3'4,4'-THS ～ 3,3'-DM-4,4'-DHS > 3,4-DHS ～ 3,4,4'-THS > 2,4,4'-THS > resveratrol ～ 3,5-DHS > 4,4'-DHS ～ 2,4-DHS and 3,3'4,4'-THS ～ 3,4-DHS ～ 3,4,4'-THS > 3,3'-DM-4,4'-DHS > 4,4'-DHS > resveratrol ～ 2,4-DHS > 2,4,4'-THS ～ 3,5-DHS, respectively. Molecules bearing ortho-dihydroxyl or 4-hydroxy-3-methoxyl groups possess significantly higher antioxidant activity than those bearing no such functionalities.