5-HT3 receptor blocking activity of arylalkanes isolated from the rhizome of Zingiber officinale

Different extracts (ethanolic, hexane, aqueous) of ginger (rhizomes of Zingiber officinale) and the essential oil were tested using [C-14]guanidinium influx into N1E-115 cells and the isolated rat ileum in order to identify their activity in inhibiting 5-HT3 receptor function. The hexane extract proved to be the most active and yielded upon bioassay-guided fractionation nine constituents: [6]-, [8]-, [10]-gingerols, [6]- and [8]-shogaols which were previously shown as active in vivo against cytotoxic drug-induced emesis; [4]-gingerol, [6]-gingerdiol, diacetyl-[6]-gingerdiol and [6]-dehydrogingerdione have not been previously tested for anti-emetic or 5-HT3 receptor antagonistic effects. Even though the latter four compounds are only minor constituents, their identification contributed towards the characterisation of a structure-activity relationship of this class of compounds. The order of potency for the nine constituents in the N1E-115 cell system was [6]-gingerdiol diacetyl-[6]-gingerdiol [6]-dehydrogingerdione [6]-shogaol >= [8]-shogaol [8]-gingerol > [10]-gingerol >= [6]-gingerol > [4]-gingerol.