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

J Ethnopharmacol. 2012 Jul 13;142(2):354-61. doi: 10.1016/j.jep.2012.04.044. Epub 2012 May 11.


Aims of the study: This 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 methods: The 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 30 min prior to a single oral administration of ranitidine (300 mg). Blood samples were collected over a 12 h 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.

Results: The 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 30-120 min 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-HT(4) receptor.

Conclusion: AFE 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-HT(4) receptor.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Area Under Curve
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Female
  • Fruit
  • Gastrointestinal Agents / pharmacology
  • Gastrointestinal Motility / drug effects*
  • Humans
  • Intestinal Absorption
  • Male
  • Middle Aged
  • Morinda / chemistry*
  • Muscle Contraction / drug effects*
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / physiology
  • Plant Extracts / pharmacology*
  • Ranitidine / blood
  • Ranitidine / pharmacokinetics*
  • Rats, Wistar
  • Receptors, Serotonin / metabolism
  • Scopoletin / pharmacology*
  • Serotonin Receptor Agonists / pharmacology
  • Stomach / drug effects*
  • Stomach / physiology
  • Young Adult


  • Gastrointestinal Agents
  • Plant Extracts
  • Receptors, Serotonin
  • Serotonin Receptor Agonists
  • Ranitidine
  • Scopoletin