title: Ferulic acid enhances the vasorelaxant effect of epigallocatechin gallate in tumor necrosis factor-alpha-induced inflammatory rat aorta.
abstract: Previously, we demonstrated synergistic enhancement of vasorelaxation by combination treatment with Trp-His and epigallocatechin gallate (EGCg) in intact rat aorta. The aim of the present study was to determine whether this vasorelaxant synergy could be recapitulated in tumor necrosis factor-alpha (TNF-α)-induced inflammatory rat aorta, and to determine the extent of its modulation by anti-inflammatory phenolic acids. Synergistic enhancement of vasorelaxation in rat aorta by Trp-His and EGCg was significantly attenuated in the presence of TNF-α, an effect that was reversed by the addition of ferulic acid (FA, 250 μM). Moreover, FA markedly enhanced EGCg-induced vasorelaxation, but not Trp-His-induced vasorelaxation, in TNF-α-treated aorta. Structure-activity analysis showed that the unsaturated 2-propenoic moiety and the methoxy group of FA were important for the enhancement of vasorelaxation by EGCg. The stimulation of EGCg-induced vasorelaxation by FA was antagonized by the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine acetate, while FA enhanced vasorelaxant properties of the endothelial nitric oxide (NO) synthase activator acetylcholine in TNF-α-treated inflammatory aorta. Moreover, the EGCg-stimulated NO production was also enhanced by FA in TNF-α-treated aorta. These data indicate that stimulation of NO production by FA enhances the vasorelaxant properties of EGCg in TNF-α-induced inflammatory aorta.
authors.affiliation: Faculty of Agriculture, Graduate School of Kyushu University, Higashi-ku, Fukuoka 812-8581, Japan.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Faculty of Agriculture, Graduate School of Kyushu University, Higashi-ku, Fukuoka 812-8581, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Suyama
authors.affiliation: Faculty of Agriculture, Graduate School of Kyushu University, Higashi-ku, Fukuoka 812-8581, Japan. Electronic address: mitsurut@agr.kyushu-u.ac.jp.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Faculty of Agriculture, Graduate School of Kyushu University, Higashi-ku, Fukuoka 812-8581, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Matsui
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D003373:Coumaric Acids / Q000494:pharmacology*; D004151:Dipeptides / Q000494:pharmacology; D004357:Drug Synergism; D008297:Male; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*; D019323:omega-N-Methylarginine
chemical_list: D001120:Arginine; D002392:Catechin; D003373:Coumaric Acids; D004151:Dipeptides; D014409:Tumor Necrosis Factor-alpha; C092506:N(G)-monomethylarginine acetate; D019323:omega-N-Methylarginine; C509582:tryptophyl-histidine; C004999:ferulic acid; C045651:epigallocatechin gallate
keywords: Epigallocatechin gallate; Ferulic acid; Inflammation; Tumor necrosis factor-alpha; Vasorelaxation