Effects of ginger constituents on the gastrointestinal tract: role of cholinergic M3 and serotonergic 5-HT3 and 5-HT4 receptors

Planta Med. 2011 Jul;77(10):973-8. doi: 10.1055/s-0030-1270747. Epub 2011 Feb 8.

Abstract

The herbal drug ginger (Zingiber officinale Roscoe) may be effective for treating nausea, vomiting, and gastric hypomotility. In these conditions, cholinergic M (3) receptors and serotonergic 5-HT (3) and 5-HT (4) 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 M (3) receptors, guinea pig 5-HT (3) receptors, and rat 5-HT (4) receptors. In whole segments of guinea pig ileum (bioassay for contractile M (3) 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-HT (3) 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-HT (4) receptors and blockade of 5-HT (1) and 5-HT (2) receptors. [6]-Shogaol (3 µM) induced depression to 61 ± 3 %. In rat esophageal tunica muscularis mucosae (bioassay for relaxant 5-HT (4) 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 M (3) and 5-HT (3) receptors. 5-HT (4) receptors, which play a role in gastroduodenal motility, appear not to be involved in the action of these compounds.

MeSH terms

  • Animals
  • Antiemetics / pharmacology
  • Catechols / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Esophagus / drug effects
  • Fatty Alcohols / pharmacology
  • Gastrointestinal Tract / drug effects*
  • Gastrointestinal Tract / physiology
  • Ginger / chemistry*
  • Guinea Pigs
  • Ileum / drug effects
  • Ileum / physiology
  • In Vitro Techniques
  • Male
  • Muscle Contraction / drug effects
  • Muscle Relaxation / drug effects
  • Myenteric Plexus / drug effects
  • Nausea / drug therapy
  • Phytotherapy
  • Plants, Medicinal
  • Rats
  • Rats, Wistar
  • Receptor, Muscarinic M3 / antagonists & inhibitors
  • Receptor, Muscarinic M3 / physiology
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Receptors, G-Protein-Coupled / drug effects*
  • Receptors, G-Protein-Coupled / physiology*
  • Receptors, Serotonin, 5-HT3 / physiology
  • Receptors, Serotonin, 5-HT4 / drug effects
  • Receptors, Serotonin, 5-HT4 / physiology
  • Serotonin Antagonists / pharmacology
  • Vomiting / drug therapy

Substances

  • Antiemetics
  • Catechols
  • Fatty Alcohols
  • Receptor, Muscarinic M3
  • Receptors, G-Protein-Coupled
  • Receptors, Serotonin, 5-HT3
  • Serotonin Antagonists
  • Receptors, Serotonin, 5-HT4
  • shogaol
  • gingerol
  • 8-gingerol