In Vivo Profiling of a Pure Alkaloid, Anatabine, in Rodents: Pharmacokinetics and Anti-Inflammatory Efficacy

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J Nat Prod. 2021 March 11th doi: 10.1021 / acs.jnatprod.0c01044. Online before printing.

ABSTRACT

Natural alkaloids, a large class of plant substances, have attracted a great deal of interest because of their pharmacological activities. This study characterized the in vivo pharmacokinetics and anti-inflammatory profile of anatabine, a naturally occurring alkaloid, in rodents. Anatabine was found to be bioavailable and brain penetrating after systemic administration. After intraperitoneal (ip) 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 at the same time increased the levels of an anti-inflammatory cytokine in a dose-dependent manner 2 hours after exposure to lipopolysaccharide. In addition, anatabine (~ 10 and ~ 20 mg / kg / day for 4 weeks; inhalation exposure) had effects on a mouse model of multiple sclerosis, reducing neurological deficits and body weight loss. Comparative studies of the pharmacokinetics and anti-inflammatory activity of anatabine demonstrated its bioequivalence in rats after IP administration and inhalation exposure. This study not only provides the first detailed profile of the pharmacokinetics of anatabine in rodents, but also comprehensively characterizes the anti-inflammatory activities of anatabine in both acute and chronic models of inflammation. These results provide a basis for further characterizing and optimizing the anti-inflammatory properties of anatabine.

PMID: 33706515 | DOI: 10.1021 / acs.jnatprod.0c01044