Anti-inflammatory effects of a bioavailable compound, Artepillin C, in Brazilian propolis

• Published in: European journal of pharmacology 2008-06, Vol.587 (1), p.296-301
• Main Authors: Paulino, Niraldo, Abreu, Sheila Rago Lemos, Uto, Yoshihiro, Koyama, Daisuke, Nagasawa, Hideko, Hori, Hitoshi, Dirsch, Verena M., Vollmar, Angelika M., Scremin, Amarilis, Bretz, Walter A.
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents; Artepillin C; Biological and medical sciences; Biological Availability; Carrageenan; Cell Survival - drug effects; Cells, Cultured; Dinoprostone - metabolism; Edema - chemically induced; Edema - prevention & control; Indicators and Reagents; Indomethacin - pharmacology; Inflammation; Intestinal Absorption; Leupeptins - pharmacology; Male; Medical sciences; Mice; NF-kappa B - metabolism; NF-κB; Nitric oxide; Nitric Oxide - metabolism; Nitrites - metabolism; Pharmacology. Drug treatments; Phenylpropionates - chemistry; Phenylpropionates - pharmacokinetics; Phenylpropionates - pharmacology; Propolis; Propolis - chemistry; Prostaglandin E 2; Transcriptional Activation
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2008.02.067

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 μg/paw), carrageenan-induced peritonitis, and prostaglandin E 2 determination. We also measured in vitro nitric oxide production by RAW 264.7 cells and NF-κB 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 μM) decreased nitric oxide production by RAW 264.7 cells with a mean IC 50 of 8.5 (7.8–9.2) μM. In HEK 293 cells, Artepillin C reduced NF-κB activity with a mean IC 50 of 26 (22–30) μg/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 μg/ml). Collectively, Artepillin C showed anti-inflammatory effects mediated, at least in part, by prostaglandin E 2 and nitric oxide inhibition through NF-κB modulation, and exhibited bioavailability by oral administration.