title: Anti-inflammatory effects of a bioavailable compound, Artepillin C, in Brazilian propolis.
abstract: Artepillin C is the major compound in the Brazilian green propolis from Baccharis dracunculifolia. Our aim in this study was to investigate the anti-inflammatory effects, absorption, and bioavailability of Artepillin C in mice. The animals used were male Swiss mice subjected to: paw oedema by carrageenan (300 microg/paw), carrageenan-induced peritonitis, and prostaglandin E(2) determination. We also measured in vitro nitric oxide production by RAW 264.7 cells and NF-kappaB activity in HEK 293 cells. Finally, we measured the absorption and bioavailability of Artepillin C in plasma from mice by means of GC-MS after a single oral dose (10 mg/kg). In vivo, Artepillin C produced a maximal inhibition of 38% after 360 min on paw oedema. Artepillin C also decreased the number of neutrophils during peritonitis (IC(50): 0.9 (0.5-1.4) mg/kg). Treatment with Artepillin C decreased prostaglandin E(2) by 29+/-3% and 58+/-5% at 1 and 10 mg/kg, respectively, with a mean ID(50) of 8.5 (8.0-8.7) mg/kg). Similarly, in in vitro models, Artepillin C (3, 10, or 100 microM) decreased nitric oxide production by RAW 264.7 cells with a mean IC(50) of 8.5 (7.8-9.2) microM. In HEK 293 cells, Artepillin C reduced NF-kappaB activity with a mean IC(50) of 26 (22-30) mug/ml), suggesting anti-inflammatory activity, particularly during acute inflammation. Lastly, Artepillin C was absorbed after an oral dose (10 mg/kg) with maximal peaks found at 1 h (22 microg/ml). Collectively, Artepillin C showed anti-inflammatory effects mediated, at least in part, by prostaglandin E(2) and nitric oxide inhibition through NF-kappaB modulation, and exhibited bioavailability by oral administration.
authors.affiliation: Programa de Pós-graduação em Farmácia, Universidade Bandeirante de São Paulo, São Paulo, Brazil. niraldop@yahoo.com.br
authors.forename: Niraldo
authors.initials: N
authors.lastname: Paulino
authors.forename: Sheila Rago Lemos
authors.initials: SR
authors.lastname: Abreu
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Uto
authors.forename: Daisuke
authors.initials: D
authors.lastname: Koyama
authors.forename: Hideko
authors.initials: H
authors.lastname: Nagasawa
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hori
authors.forename: Verena M
authors.initials: VM
authors.lastname: Dirsch
authors.forename: Angelika M
authors.initials: AM
authors.lastname: Vollmar
authors.forename: Amarilis
authors.initials: A
authors.lastname: Scremin
authors.forename: Walter A
authors.initials: WA
authors.lastname: Bretz
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents; D001682:Biological Availability; D002351:Carrageenan; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D007202:Indicators and Reagents; D007213:Indomethacin / Q000494:pharmacology; D007408:Intestinal Absorption; D007976:Leupeptins / Q000494:pharmacology; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D010666:Phenylpropionates / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D011429:Propolis / Q000737:chemistry*; D015533:Transcriptional Activation
chemical_list: D000893:Anti-Inflammatory Agents; D007202:Indicators and Reagents; D007976:Leupeptins; D016328:NF-kappa B; D009573:Nitrites; D010666:Phenylpropionates; D009569:Nitric Oxide; C102259:artepillin C; D002351:Carrageenan; D011429:Propolis; D015232:Dinoprostone; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde; D007213:Indomethacin