Caffeic acid derivatives: in vitro and in vivo anti-inflammatory properties.
Caffeic acid and some of its derivatives such as caffeic acid phenetyl ester (CAPE) and octyl caffeate are potent antioxidants which present important anti-inflammatory actions. The present study assessed the in vitro and in vivo effects of five caffeic acid derivatives (caffeic acid methyl, ethyl, butyl, octyl and benzyl esters) and compared their actions to those of CAPE. In the model of LPS-induced nitric oxide (NO) production in RAW 264.7 macrophages, the pre-incubation of all derivatives inhibited nitrite accumulation on the supernatant of stimulated cells, with mean IC50 (microM) values of 21.0, 12.0, 8.4, 2.4, 10.7 and 4.80 for methyl, ethyl, butyl, octyl, benzyl and CAPE, respectively. The effects of caffeic acid derivatives seem to be related to the scavenging of NO, as the compounds prevented SNAP-derived nitrite accumulation and decreased iNOS expression. In addition, butyl, octyl and CAPE derivatives significantly inhibited LPS-induced iNOS expression in RAW 264.7 macrophages. Extending the in vitro results, we showed that the pre-treatment of mice with butyl, octyl and CAPE derivatives inhibited carrageenan-induced paw edema and prevented the increase in IL-1beta levels in the mouse paw by 30, 24 and 36%, respectively. Butyl, octyl and CAPE derivatives also prevented carrageenan-induced neutrophil influx in the mouse paw by 28, 49 and 31%, respectively. Present results confirm and extend literature data, showing that caffeic acid derivatives exert in vitro and in vivo anti-inflammatory actions, being their actions mediated, at least in part by the scavenging of NO and their ability to modulate iNOS expression and probably that of other inflammatory mediators.
da Cunha
Fernanda M
FM
Department of Pharmacology, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade 88049-900, Florianópolis, SC, Brazil.
Duma
Danielle
D
Assreuy
Jamil
J
Buzzi
Fátima C
FC
Niero
Rivaldo
R
Campos
Maria M
MM
Calixto
João B
JB
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000494:pharmacology*; D002109:Caffeic Acids / Q000737:chemistry* / Q000494:pharmacology*; D002351:Carrageenan / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D004952:Esters / Q000737:chemistry / Q000494:pharmacology; D005121:Extremities / Q000473:pathology; D020128:Inhibitory Concentration 50; D007375:Interleukin-1 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D015394:Molecular Structure; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D002109:Caffeic Acids; D004952:Esters; D007375:Interleukin-1; D008070:Lipopolysaccharides; D009573:Nitrites; D009569:Nitric Oxide; D002351:Carrageenan; D009195:Peroxidase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C040048:caffeic acid