Gastrokinetic activity of Morinda citrifolia aqueous fruit extract and its possible mechanism of action in human and rat models

Abstract

Aims of the studyThis study was to investigate the gastrokinetic activity of Morinda citrifolia aqueous fruit extract (AFE) in human subjects by examining the GI absorption of ranitidine, a putative indicator of GI motility and to elucidate its possible gastrokinetic mechanism of action in rats. Materials and methodsThe single-dose, randomized, open-label and 2-period crossover study was performed on 20 Thai healthy volunteers with a washout period of 14 day between the doses. AFE or drinking water was administered orally 30min prior to a single oral administration of ranitidine (300mg). Blood samples were collected over a 12h period after drug administration and the pharmacokinetic parameters of ranitidine were calculated. The gastrokinetic mechanism of action of AFE was elucidated by measurement of its contractile response on the isolated rat gastric fundus strip. ResultsThe area under the plasma ranitidine concentration–time curve and the maximal plasma ranitidine concentration were significantly increased after pretreatment with AFE (p=0.001). The plasma ranitidine concentrations were significantly greater at 30–120min after its administration. AFE produced a definite contractile response of a rat gastric fundus strip with a dose dependency. Scopoletin at the same equivalent dose present in AFE elicited a concentration-dependent contraction that amounted to 45% of the maximal response to AFE. The contractile response of both AFE and scopoletin was mediated through the 5-HT4 receptor. ConclusionAFE has a unique gastrokinetic activity in enhancement of the rate and the extent of ranitidine absorption. The underlying mechanism can be attributed, at least in part, to the ability of its active component: scopoletin to stimulate the 5-HT4 receptor.