| Autor: |
Xia W; Philip Morris International Research Laboratories Pte Ltd, 50 Science Park Road, Singapore 117406., Kolli AR; Philip Morris Products S.A., Quai Jeanrenaud 5, Neuchatel, CH-2000, Switzerland., Koshibu K; Philip Morris Products S.A., Quai Jeanrenaud 5, Neuchatel, CH-2000, Switzerland., Martin F; Philip Morris Products S.A., Quai Jeanrenaud 5, Neuchatel, CH-2000, Switzerland., Kondylis A; Philip Morris Products S.A., Quai Jeanrenaud 5, Neuchatel, CH-2000, Switzerland., Kuczaj A; Philip Morris Products S.A., Quai Jeanrenaud 5, Neuchatel, CH-2000, Switzerland., Tan WT; Philip Morris International Research Laboratories Pte Ltd, 50 Science Park Road, Singapore 117406., Yeo YS; Philip Morris International Research Laboratories Pte Ltd, 50 Science Park Road, Singapore 117406., Tan G; Philip Morris International Research Laboratories Pte Ltd, 50 Science Park Road, Singapore 117406., Teng C; Philip Morris International Research Laboratories Pte Ltd, 50 Science Park Road, Singapore 117406., Woon K; Philip Morris International Research Laboratories Pte Ltd, 50 Science Park Road, Singapore 117406., Schneider T; Philip Morris Products S.A., Quai Jeanrenaud 5, Neuchatel, CH-2000, Switzerland., Talikka M; Philip Morris Products S.A., Quai Jeanrenaud 5, Neuchatel, CH-2000, Switzerland., Phillips BW; Philip Morris International Research Laboratories Pte Ltd, 50 Science Park Road, Singapore 117406., Vanscheeuwijck P; Philip Morris Products S.A., Quai Jeanrenaud 5, Neuchatel, CH-2000, Switzerland., Peitsch MC; Philip Morris Products S.A., Quai Jeanrenaud 5, Neuchatel, CH-2000, Switzerland., Hoeng J; Philip Morris Products S.A., Quai Jeanrenaud 5, Neuchatel, CH-2000, Switzerland. |
| Abstrakt: |
Natural alkaloids, a large class of plant-derived substances, have attracted considerable interest because of their pharmacological activities. In this study, the in vivo pharmacokinetics and anti-inflammatory profile of anatabine, a naturally occurring alkaloid, were characterized in rodents. Anatabine was found to be bioavailable and brain-penetrant following systemic administration. Following intraperitoneal (i.p.) administration (1, 2, and 5 mg/kg), anatabine caused a dose-dependent reduction in carrageenan-induced paw edema in rats; in mice, it inhibited the production of pro-inflammatory cytokines and simultaneously elevated the levels of an anti-inflammatory cytokine in a dose-dependent manner 2 h after lipopolysaccharide challenge. Furthermore, anatabine (∼10 and ∼20 mg/kg/day for 4 weeks; inhalation exposure) had effects in a murine model of multiple sclerosis, reducing neurological deficits and bodyweight loss. Comparative studies of the pharmacokinetics and anti-inflammatory activity of anatabine demonstrated its bioequivalence in rats following i.p. administration and inhalation exposure. This study not only provides the first detailed profile of anatabine pharmacokinetics in rodents but also comprehensively characterizes the anti-inflammatory activities of anatabine in acute and chronic inflammatory models. These findings provide a basis for further characterizing and optimizing the anti-inflammatory properties of anatabine. |
