Antioxidant activity of hydroxycinnamic acid derivatives in human low density lipoprotein: Mechanism and structure–activity relationship

Hydroxycinnamic acid derivatives, i.e., caffeic acid (CaA), chlorogenic acid (ChA), sinapic acid (SA), ferulic acid (FA) and p-coumaric acid (CoA), are widely distributed in plants and are known antioxidants. The in vitro peroxidation of human low density lipoprotein (LDL) was used as a model to study the free radical-induced damage of biological membranes and the protective effect of hydroxycinnamic acid derivatives. The peroxidation was initiated either by a water-soluble azo-initiator 2, 2′-azobis(2-amidinopropane hydrochloride) (AAPH), or by cupric ion (Cu2+). The reaction kinetics were monitored either by the uptake of oxygen or by the formation of thiobarbituric acid reactive substances (TBARS). Kinetic analysis of the antioxidation process demonstrates that these hydroxycinnamic acid derivatives are effective antioxidants against both AAPH- and Cu2+-induced LDL peroxidation with the activity sequence of CaA ∼ ChA > SA > FA > CoA, and CaA ∼ ChA > SA ∼ FA ∼ CoA, respectively. Molecules bearing ortho-dihydroxyl or 4-hydroxy-3-methoxyl groups possess significantly higher antioxidant activity than those bearing no such functionalities.