Effect of ginseng saponins on the recombinant serotonin type 3A receptor expressed in xenopus oocytes: implication of possible application as an antiemetic.
OBJECTIVE
Nausea and vomiting are the most frequently reported side-effects by patients who are given general anesthesia perioperatively and patients with cancer who undergo chemotherapy or radiotherapy. Serotonin (5-hydroxytryptamine, 5HT) type 3A receptor (5HT(3A) receptor) is known to mediate nausea and vomiting and its antagonists have been used effectively to prevent and/or reduce the incidence and severity of nausea and vomiting. However, the adverse effects on cardiac function, such as QT interval prolongation, limit their routine use by these patients. This study was designed to elucidate the effect of ginseng saponins on the recombinant 5HT(3A) receptor expressed in the xenopus oocyte.


METHODS
After in vitro transcription of the recombinant human 5HT(3A) receptor in the Xenopus laevis oocyte, we examined Panax ginseng saponins (total saponin [TS], panaxadiol saponin [PD] fraction, panaxatriol saponin [PT] fraction, and ginsenoside-Rb1 and -Rg1) for their ability to inhibit current flow through the 5HT(3A) receptor using the voltage-clamp technique.


RESULTS
All saponin fractions (TS, PD, PT fraction, as well as ginsenoside-Rb1 and -Rg1) inhibited the peak current induced by the agonist 5HT on the 5HT(3A) receptor in a concentration-dependent, reversible, and voltage-independent manner. The PT fraction inhibited 5HT-induced currents in 5HT(3A) receptor more than the PD fraction; meanwhile, there was a similar degree of inhibition between ginsenoside-Rg1 and -Rb1, the main substitutes of PT fraction and PD saponin fractions, respectively.


CONCLUSIONS
These results indicate that ginseng saponins, especially PT fraction, have substantial inhibitory effects on the recombinant 5HT(3A) receptor, suggesting that some of the specific types of ginsenoside might have an antagonistic action against 5HT(3A) receptor related to nausea and vomiting.
D000818:Animals; D000932:Antiemetics / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D036145:Ginsenosides / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D066298:In Vitro Techniques; D009325:Nausea / Q000517:prevention & control; D009865:Oocytes / Q000378:metabolism*; D005894:Panax; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000096:biosynthesis; D044406:Receptors, Serotonin, 5-HT3 / Q000187:drug effects* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000187:drug effects / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology; D014315:Triterpenes / Q000494:pharmacology; D014839:Vomiting / Q000517:prevention & control; D014982:Xenopus laevis
D000932:Antiemetics; D036145:Ginsenosides; D012333:RNA, Messenger; D044406:Receptors, Serotonin, 5-HT3; D011994:Recombinant Proteins; D012503:Saponins; D014315:Triterpenes; C004563:panaxatriol