Larissa Gabriela Faqueti1, Layzon Antonio Lemos da Silva1, Gabriela Salim Gomes Moreira1, Scheila Kraus2, Gustavo Dos Santos Catarina de Jesus2, Luciana Aparecida Honorato3, Bibiana Verlindo de Araujo4, Adair Roberto Soares Dos Santos2, Teresa Dalla Costa4, Maique Weber Biavatti5,6. 1. Department of Pharmaceutical Sciences, CCS, Universidade Federal de Santa Catarina - UFSC, Florianópolis, SC, Brazil. 2. Department of Physiological Sciences, CCB, Universidade Federal de Santa Catarina - UFSC, Florianópolis, SC, Brazil. 3. Department of Pharmacology, CCB, Universidade Federal de Santa Catarina - UFSC, Florianópolis, SC, Brazil. 4. Pharmacokinetics and PK/PD Modelling Laboratory, College of Pharmacy, Universidade Federal Do Rio Grande do Sul - UFRGS, Porto Alegre, RS, Brazil. 5. Department of Pharmaceutical Sciences, CCS, Universidade Federal de Santa Catarina - UFSC, Florianópolis, SC, Brazil. maique.biavatti@ufsc.br. 6. Farmacognosy Laboratory, CIF/CCS, UFSC Campus Universitário/Trindade, Florianópolis, SC, 88040-900, Brazil. maique.biavatti@ufsc.br.
Abstract
PURPOSE: 5'-methoxynobiletin (5'-MeONB), a polymethoxyflavone isolated from A. conyzoides, has shown anti-inflammatory property. Nevertheless, the antinociceptive activity and pre-clinical pharmacokinetics (PK) characteristics of 5'-MeONB remain unknown. Considering the anti-inflammatory potential of the 5'-MeONB, this study aimed to investigate the pre-clinical PK behavior of 5'-MeONB, as well as its time course antinociceptive activity. METHODS: 5'-MeONB plasma concentrations were determined in Wistar rats after intravenous (i.v.) (10 mg/kg) and oral (50 mg/kg) administration, and in Swiss mice after oral administration (100 mg/kg). Plasma samples were deproteinization and 5'-MeONB quantified by a validated UPLC-MS method. Additionally, the antinociceptive activity of 5'-MeONB was evaluated after 15, 30, 60, 180 and 360 min following oral administration on the acute nocifensive behavior of mice induced by formalin. RESULTS: 5'-MeONB rats and mice plasma concentration-time profiles were best one-compartment model. After i.v. administration to rats, a short half-life, a high clearance and moderate volume of distribution at steady state were observed. Similar results were obtained after oral administration. The oral bioavailability ranged from 8 to 11%. Additionally, 5'-MeONB exhibited antinociceptive activity in both formalin phases, especially in the inflammatory phase of the model, inhibiting 68% and 91% of neurogenic and inflammatory responses, respectively, after 30 min of oral administration. CONCLUSIONS: The results described here provide novel insights on 5'-MeONB pharmacokinetics and pharmacodynamic effect, serving as support for future studies to confirm this compound as anti-nociceptive and anti-inflammatory effective agent.
PURPOSE: 5'-methoxynobiletin (5'-MeONB), a polymethoxyflavone isolated from A. conyzoides, has shown anti-inflammatory property. Nevertheless, the antinociceptive activity and pre-clinical pharmacokinetics (PK) characteristics of 5'-MeONB remain unknown. Considering the anti-inflammatory potential of the 5'-MeONB, this study aimed to investigate the pre-clinical PK behavior of 5'-MeONB, as well as its time course antinociceptive activity. METHODS: 5'-MeONB plasma concentrations were determined in Wistar rats after intravenous (i.v.) (10 mg/kg) and oral (50 mg/kg) administration, and in Swiss mice after oral administration (100 mg/kg). Plasma samples were deproteinization and 5'-MeONB quantified by a validated UPLC-MS method. Additionally, the antinociceptive activity of 5'-MeONB was evaluated after 15, 30, 60, 180 and 360 min following oral administration on the acute nocifensive behavior of mice induced by formalin. RESULTS: 5'-MeONB rats and mice plasma concentration-time profiles were best one-compartment model. After i.v. administration to rats, a short half-life, a high clearance and moderate volume of distribution at steady state were observed. Similar results were obtained after oral administration. The oral bioavailability ranged from 8 to 11%. Additionally, 5'-MeONB exhibited antinociceptive activity in both formalin phases, especially in the inflammatory phase of the model, inhibiting 68% and 91% of neurogenic and inflammatory responses, respectively, after 30 min of oral administration. CONCLUSIONS: The results described here provide novel insights on 5'-MeONB pharmacokinetics and pharmacodynamic effect, serving as support for future studies to confirm this compound as anti-nociceptive and anti-inflammatory effective agent.
Authors: Larissa G Faqueti; Vincent Brieudes; Maria Halabalaki; Alexios L Skaltsounis; Leandro F Nascimento; Wellinghton M Barros; Adair R S Santos; Maique W Biavatti Journal: J Ethnopharmacol Date: 2016-09-12 Impact factor: 4.360
Authors: Sheikh Fayaz Ahmad; Sabry M Attia; Saleh A Bakheet; Khairy M A Zoheir; Mushtaq Ahmad Ansari; Hesham M Korashy; Hala E Abdel-Hamied; Abdelkader E Ashour; Adel R A Abd-Allah Journal: Inflammation Date: 2015-04 Impact factor: 4.092
Authors: Sylvia Vogl; Paolo Picker; Judit Mihaly-Bison; Nanang Fakhrudin; Atanas G Atanasov; Elke H Heiss; Christoph Wawrosch; Gottfried Reznicek; Verena M Dirsch; Johannes Saukel; Brigitte Kopp Journal: J Ethnopharmacol Date: 2013-06-13 Impact factor: 4.360