Ginger has been used since ancient times for the treatment of nausea and vomiting. More recently, short clinical trials have demonstrated the effectiveness of this herb in the treatment of nausea and vomiting during pregnancy and in chemotherapy-induced nausea and vomiting (CINV). Patients with functional gastrointestinal disorders, such as IBS and functional dyspepsia, might also benefit from treatment with ginger, although the evidence is less robust in this setting.
Studies have suggested that the antiemetic effect of ginger might be mediated via 5-HT3 receptors. Most work in this field has been conducted in cell lines or gut samples from mice. “With our work, we wanted to unravel the mode of action of ginger in the human system,” says Beate Niesler from the Department of Human Molecular Genetics, Institute of Human Genetics, Heidelberg, Germany. “It is well known that rodents differ from humans with regard to the 5-HT3 receptor system.”
Niesler and colleagues therefore used calcium influx assays and ligand binding studies to investigate the effect of ginger on homomeric 5-HT3A and heteromeric 5-HT3AB receptors in a human cell line (HEK293 cells) as well as in human submucous plexus material (in collaboration with Michael Schemann, Technical University, Munich, Germany).
“We could prove that ginger and its pungent components act in an antagonistic manner on human homomeric 5-HT3A and heteromeric 5-HT3AB as well as native 5-HT3 receptors on enteric neurons from the submucous plexus,” reports Niesler. Furthermore, the researchers demonstrated that the 5-HT3 receptor binding site for the active constituent of ginger is different to that for the 'setrons' (for example, ondansetron and alosetron). The setrons are another class of agents that interact with 5-HT3 receptors and are the gold standard for treatment of CINV. This finding means that the combination of ginger and a setron would exert an additive inhibitory effect on 5-HT3 receptors. In fact, clinical trials involving patients with cancer receiving setrons for the treatment of CINV have demonstrated reduced incidence of nausea in patients who also received ginger.
The researchers hope that their findings might encourage longer clinical trials assessing the safety of ginger extracts in various settings. They are also interested in following up the mode of action of other natural compounds.
ORIGINAL RESEARCH PAPER
Walstab, J. et al. Ginger and its pungent constituents non-competitively inhibit activation of human recombinant and native 5-HT3 receptors of enteric neurons. Neurogastroenterol. Motil. doi:10.1111/nmo.12107
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Leake, I. Getting to the root of the antiemetic effects of ginger. Nat Rev Gastroenterol Hepatol 10, 259 (2013). https://doi.org/10.1038/nrgastro.2013.54