Inhibition of human low-density lipoprotein oxidation by caffeic acid and other hydroxycinnamic acid derivatives

Abstract

The antioxidant activity of the major phenols derived from hydroxycinnamic acid (caffeic, ferulic, and p-coumaric acids) on in vitro LDL oxidation was screened, using Cu2+ as catalyst. The presence of the second phenolic hydroxy group enhanced the inhibitory effect of these compounds. In fact, at 5 microM concentration, only caffeic acid completely protected LDL from modification as measured as conjugated dienes formation and apo B-100 fragmentation, also preserving alpha-tocopherol. The effect of caffeic acid in inhibiting LDL oxidative modification induced by three different oxidant systems was tested. Using both Cu2+ and 2,2'-azobis (2-amidinopropane)-hydrochloride (AAPH), the inhibitory effect of caffeic acid was dose-dependent. Yet, the better protection was achieved in the metal-ion dependent system. Also the murine macrophages-mediated LDL oxidation was efficiently inhibited by 5 microM caffeic acid. UV-VIS spectra of caffeic acid incubated with cupric ions show the formation of a caffeic acid:copper complex, responsible for a transient chelating activity. This mechanism, coupled with its free radical scavenging property, accounts for the higher inhibitory activity exhibited by caffeic in Cu(2+)-catalyzed reaction.