Inhibition of human low-density lipoprotein oxidation by caffeic acid and other hydroxycinnamic acid derivatives.
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.
Istituto Nazionale della Nutrizione, Roma, Italy.
M
M
Nardini
M
M
D'Aquino
G
G
Tomassi
V
V
Gentili
M
M
Di Felice
C
C
Scaccini
D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002109:Caffeic Acids / Q000494:pharmacology*; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008054:Lipid Peroxides / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013329:Structure-Activity Relationship
D000975:Antioxidants; D002109:Caffeic Acids; D002839:Chromans; D008054:Lipid Peroxides; D008077:Lipoproteins, LDL; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; C040048:caffeic acid