Effects of Ginger Constituents on the Gastrointestinal Tract: Role of Cholinergic M₃ and Serotonergic 5-HT₃ and 5-HT₄ Receptors

Abstract

The herbal drug ginger (Zingiber officinale Roscoe) may be effective for treating nausea, vomiting, and gastric hypomotility. In these conditions, cholinergic M₃ receptors and serotonergic 5-HT₃ and 5-HT₄ receptors are involved. The major chemical constituents of ginger are [6]-gingerol, [8]-gingerol, [10]-gingerol, and [6]-shogaol. We studied the interaction of [6]-gingerol, [8]-gingerol, [10]-gingerol (racemates), and [6]-shogaol with guinea pig M₃ receptors, guinea pig 5-HT₃ receptors, and rat 5-HT₄ receptors. In whole segments of guinea pig ileum (bioassay for contractile M₃ receptors), [6]-gingerol, [8]-gingerol, [10]-gingerol, and [6]-shogaol slightly but significantly depressed the maximal carbachol response at an antagonist concentration of 10 µM. In the guinea pig myenteric plexus preparation (bioassay for contractile 5-HT₃ receptors), 5-HT maximal responses were depressed by [10]-gingerol from 93 ± 3 % to 65 ± 6 % at an antagonist concentration of 3 µM and to 48 ± 3 % at an antagonist concentration of 5 µM following desensitization of 5-HT₄ receptors and blockade of 5-HT₁ and 5-HT₂ receptors. [6]-Shogaol (3 µM) induced depression to 61 ± 3 %. In rat esophageal tunica muscularis mucosae (bioassay for relaxant 5-HT₄ receptors), [6]-gingerol, [8]-gingerol, [10]-gingerol, and [6]-shogaol (2–6.3 µM) showed no agonist effects. The maximal 5-HT response remained unaffected in the presence of the compounds. It is concluded that the efficiency of ginger in reducing nausea and vomiting may be based on a weak inhibitory effect of gingerols and shogaols at M₃ and 5-HT₃ receptors. 5-HT₄ receptors, which play a role in gastroduodenal motility, appear not to be involved in the action of these compounds.

ginger - Zingiber officinale Roscoe - Zingiberaceae - gastrointestinal diseases - cholinergic M₃ receptors - 5‐HT₃ receptors - 5‐HT₄ receptors

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