Mode of action of gingerols and shogaols on 5-HT3 receptors: Binding studies, cation uptake by the receptor channel and contraction of isolated guinea-pig ileum

Abdel-Aziz, H; Windeck, Timo; Ploch, M.; Verspohl, Eugen J.

doi:10.1016/j.ejphar.2005.10.049

Cited by 133 publications

(89 citation statements)

References 17 publications

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“…We detected only a weak antagonism for the vanilloids vanillin, creosol and eugenol and for isovanillin. 5-HT 3A -receptor antagonism increases with longer side chains in the para configuration to the hydroxygroup of the aromatic ring of vanilloids, reaching a maximum for 8-gingerol, which is consistent with the data of the murine 5-HT 3A receptor [35].…”

Section: A C C E P T E D Accepted Manuscriptsupporting

confidence: 86%

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Activation and modulation of recombinantly expressed serotonin receptor type 3A by terpenes and pungent substances

Ziemba

Schreiner

Flegel

et al. 2015

Biochemical and Biophysical Research Communications

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Section: A C C E P T E D Accepted Manuscriptsupporting

confidence: 86%

“…The best characterized constituents are gingerols and shogaols, which block the acetylcholine-induced contraction of the guinea-pig ileum in vitro [35]. Most recently, the action of gingerol on recombinantly expressed receptors using a calcium-based assay was investigated [11].…”

Section: Discussionmentioning

confidence: 99%

Activation and modulation of recombinantly expressed serotonin receptor type 3A by terpenes and pungent substances

Ziemba

Schreiner

Flegel

et al. 2015

Biochemical and Biophysical Research Communications

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“…Gingerol is the generic term of pungent constituents in ginger (Jiang et al, 2006). It has been reported that gingerol displays inhibitive effect on contraction of isolated guinea-pig ileum by acting on 5-HT 3 receptors and presumed to be related to the antiememtic activity (Abdel-Aziz et al, 2006). However, the antiemetic mechanism of gingerol remains unclear, and there are few reports of the study from multi-targets.…”

Section: Introductionmentioning

confidence: 97%

Gingerol inhibits cisplatin-induced vomiting by down regulating 5-hydroxytryptamine, dopamine and substance P expression in minks

Qian

Wang

et al. 2009

Arch. Pharm. Res.

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To investigate the antiemetic effect of gingerol and its multi-targets effective mechanism on 5-hydroxytryptamine (5-HT), dopamine (DA) and substance P (SP). The antiemetic effect of gingerol was investigated on a vomiting model of mink induced by cisplatin (7.5 mg . kg(-1), i.p.) in 6 h observation. The levels of 5-HT, DA and distribution of substance P in the area postrema and ileum were measured by high performance liquid chromatography (HPLC) and immunohistochemistry respectively. The frequency of cisplatin induced retching and vomiting was significantly reduced by pretreatment with gingerol in a dose-dependent manner (P<0.05). Cisplatin produced a significant increase in 5-HT and DA levels in the area postrema and ileum of minks (P<0.05), and this increase was significantly inhibited by gingerol in a dose-dependent manner (P<0.05). Substance P-immunoreactive was mainly situated in the mucosa and submucosa of ileum as well as in the neurons of area postrema, and gingerol markedly suppressed the increase immunoreactivity of substance P induced by cisplatin in a dose-dependent manner (P<0.05). Gingerol has good activity against cisplatin-induced emesis in minks possibly by inhibiting central or peripheral increase of 5-HT, DA and substance P.

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“…[26] The principle compounds in ginger, gingerols and shogaols, have been demonstrated to inhibit serotonin-mediated signaling and that this interaction could be mediated through a currently unidentified binding site. [27] , [28,29] In vitro studies by Abdel Aziz found that 6S, 6G, 8G and 10G inhibited 5-HT3-induced contractions of the isolated guinea-pig ileum. Since these same compounds were unable to displace the competitive antagonist,…”

Section: Introductionmentioning

confidence: 99%

In silico investigation into the interactions between murine 5-HT3 receptor and the principle active compounds of ginger (Zingiber officinale)

Lohning

Marx

Isenring

2016

Journal of Molecular Graphics and Modelling

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. In silico investigation into the interactions between murine 5-HT3 receptor and the principle active compounds of ginger (Zingiber officinale).. Retrieved from http://dx.doi. org/10.1016/j.jmgm.2016.10.008 1 Abstract Gingerols and shogaols are the primary non-volatile actives within ginger (Zingiber officinale).These compounds have demonstrated in vitro to exert 5-HT3 receptor antagonism which could benefit chemotherapy-induced nausea and vomiting (CINV). The site and mechanism of action by which these compounds interact with the 5-HT3 receptor is not fully understood although research indicates they may bind to a currently unidentified allosteric binding site. Using in silico techniques, such as molecular docking and GRID analysis, we have characterized the recently available murine 5-HT3 receptor by identifying sites of strong interaction with particular functional groups at both the orthogonal (serotonin) site and a proposed allosteric binding site situated at the interface between the transmembrane region and the extracellular domain. These were assessed concurrently with the top-scoring poses of the docked ligands and included key active gingerols, shogaols and dehydroshogaols as well as competitive antagonists (e.g. setron class of pharmacologically active drugs), serotonin and its structural analogues, curcumin and capsaicin, non-competitive antagonists and decoys. Unexpectedly, we found that the ginger compounds and their structural analogs generally outscored other ligands at both sites. Our results correlated well with previous site-directed mutagenesis studies in identifying key binding site residues. We have identified new residues important for binding the ginger compounds. Overall, the results suggest that the ginger compounds and their structural analogues possess a high binding affinity to both sites. Notwithstanding the limitations of such theoretical analyses, these results suggest that the ginger compounds could act both competitively or non-competitively as has been shown for palonosetron and other modulators of CYS loop receptors. KeywordsGinger antiemetic Zingiber officinale gingerol shogaols chemotherapy induced nausea vomiting 2

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Mode of action of gingerols and shogaols on 5-HT3 receptors: Binding studies, cation uptake by the receptor channel and contraction of isolated guinea-pig ileum

Cited by 133 publications

References 17 publications

Activation and modulation of recombinantly expressed serotonin receptor type 3A by terpenes and pungent substances

Activation and modulation of recombinantly expressed serotonin receptor type 3A by terpenes and pungent substances

Gingerol inhibits cisplatin-induced vomiting by down regulating 5-hydroxytryptamine, dopamine and substance P expression in minks

In silico investigation into the interactions between murine 5-HT3 receptor and the principle active compounds of ginger (Zingiber officinale)

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