Niraldo Paulino a,b,⁎, Sheila Rago Lemos Abreu a,b, Yoshihiro Uto c, Daisuke Koyama c, Hideko Nagasawa c, Hitoshi Hori c, Verena M. Dirsch d, Angelika M. Vollmar d, Amarilis Scremin e, Walter A. Bretz f
a Programa de Pós-graduação em Farmácia, Universidade Bandeirante de São Paulo, São Paulo, Brazil
b Pharmacy Department, Centro Universitário Barriga Verde, Orleans, Brazil
c Department of Life System, Institute of Technology and Science, The University of Tokushima Graduate School, Minamijosanjimacho-2, Tokushima, Japan d Dpartment of Pharmacy, University of Munich, Munich, Germany
e Departament of Pharmancy, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil
f New York University, College of Dentistry, New York, NY, USA
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 E2 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 (IC50: 0.9 (0.5–1.4) mg/kg). Treatment with Artepillin C decreased prostaglandin E2 by 29±3% and 58±5% at 1 and 10 mg/kg, respectively, with a mean ID50 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 IC50 of 8.5 (7.8–9.2) μM. In HEK 293 cells, Artepillin C reduced NF-κB activity with a mean IC50 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 E2 and nitric oxide inhibition through NF-κB modulation, and exhibited bioavailability by oral administration.
* THESE STATEMENTS HAVE NOT BEEN EVALUATED BY THE FOOD AND DRUG ADMINISTRATION. THIS IS NOT INTENDED TO DIAGNOSE, TREAT CURE OR PREVENT ANY DISEASE.