ABSTRACT
Urushiols consist of an o-dihydroxybenzene (catechol) structure and an alkyl chain of 15 or 17 carbons in the 3-position of a benzene ring and are allergens found in the family Anacardiaceae. We synthesized various veratrole (1,2-dimethoxybenzene)-type and catechol-type urushiol derivatives that contained alkyl chains of various carbon atom lengths, including -H, -C1H3, -C5H11, -C10H21, -C15H31, and -C20H41, and investigated their contact hypersensitivities and antioxidative activities. 3-Decylcatechol and 3-pentadecylcatechol displayed contact hypersensitivity, but the other compounds did not induce an allergic reaction, when the ears of rats were sensitized by treatment with the compounds every day for 20 days. Catechol-type urushiol derivatives (CTUDs) exerted very high radical-scavenging activity on the 1,1-diphenyl-2-picrylhydrazyl radical and inhibited lipid peroxidation in a methyl linoleate solution induced by 2,2'-azobis(2,4-dimethylvaleronitrile) (AMVN). However, veratrole-type urushiol derivatives did not scavenge or inhibit lipid peroxidation. CTUDs also acted as effective inhibitors of lipid peroxidation of the egg yolk phosphatidylcholine large unilamellar vesicle (PC LUV) liposome system induced by various radical generators such as AMVN, 2,2'-azobis(2-amidino-propane) dihydrochloride, and copper ions, although their efficiencies differed slightly. In addition, CTUDs suppressed formation of cholesteryl ester hydroperoxides in rat blood plasma induced with copper ions. CTUDs containing more than five carbon atoms in the alkyl chain showed excellent lipophilicity in a n-octanol/water partition experiment. These compounds also exhibited high affinities to the liposome membrane using the ultrafiltration method of the PC LUV liposome system. Therefore, CTUDs seem to act as efficient antioxidative compounds against membranous lipid peroxidation owing to their localization in the phospholipid bilayer. These results suggest that nonallergenic CTUDs act as antioxidants to protect against oxidative damage of cellular and subcellular membranes.
Subject(s)
Anisoles/chemistry , Catechols/chemistry , Free Radical Scavengers/chemistry , Unilamellar Liposomes/chemistry , Animals , Anisoles/pharmacology , Azo Compounds/antagonists & inhibitors , Biphenyl Compounds/antagonists & inhibitors , Catechols/pharmacology , Cholesterol Esters/chemistry , Copper/chemistry , Dermatitis, Contact/blood , Dermatitis, Contact/immunology , Ear, External/drug effects , Ear, External/immunology , Free Radical Scavengers/pharmacology , Linoleic Acids/chemistry , Male , Nitriles/antagonists & inhibitors , Oxidation-Reduction , Phosphatidylcholines/chemistry , Picrates/antagonists & inhibitors , Rats , Rats, Sprague-Dawley , Structure-Activity RelationshipABSTRACT
Two novel caffeoylmalic acid methyl esters, 2-O-(trans-caffeoyl)malic acid 1-methyl ester (6) and 2-O-(trans-caffeoyl)malic acid 4-methyl ester (7), were isolated from pear (Pyrus pyrifolia Nakai cv. Chuhwangbae) fruit peels. In addition, 5 known hydroxycinnamoylmalic acids and their methyl esters were identified: 2-O-(trans-coumaroyl)malic acid (1), 2-O-(cis-coumaroyl)malic acid (2), 2-O-(cis-coumaroyl)malic acid 1-methyl ester (3), 2-O-(trans-coumaroyl)malic acid 1-methyl ester (4), and 2-O-(trans-caffeoyl)malic acid (phaselic acid, 5). The chemical structures of these compounds were determined by spectroscopic data from ESI MS and NMR. Of all the isolated compounds, five hydroxycinnamoylmalic acids and their methyl esters (2-4, 6, 7) were identified in the pear for the first time.
