The Inhibitory Effects of Korean Red Ginseng Saponins on 5- HT3AReceptor Channel Activity Are Coupled to Anti-Nausea and Anti-Vomiting Action

Abstract

We performed in vitro and in vivo studies to know whether the inhibitory effects of ginsenosides on <TEX>$5-HT_{3A}$</TEX> receptor channel acctivity are coupled to anti-nausea and anti-vomiting action. In vitro study, we investigated the effect of compound K (CK) and M4, which are ginsenoside metabolites, on human <TEX>$5-HT_{3A}$</TEX> receptor channel activity expressed in Xenopus oocytes using two-electrode voltage clamp technique. Treatment of CK or M4 themselves had no effect in both oocytes injected with <TEX>$H_2O\;and\;5-HT_{3A}$</TEX> receptor cRNA. In oocytes injected with <TEX>$5- HT_{3A}$</TEX> receptor cRNA, M4 treatment inhibited more potently 5-HT-induced inward peak current <TEX>$(I_{5-HT})$</TEX> than CK with dose-dependent and reversible manner. The half-inhibitory concentrations <TEX>$(IC_{50})$</TEX> of CK and M4 were <TEX>$36.9\;\pm\;10.1\;and\;7.3\;\pm\;2.2\;{\mu}M$</TEX>, respectively. The inhibition of <TEX>$I_{5-HT}$</TEX> by M4 was non-competitive and voltage-independent. These results indicate that M4 might regulate <TEX>$5-HT_{3A}$</TEX> receptors. In vivo experiments, injection of cisplatin (7.5 mg/kg, i.v.) induced both nausea and vomiting with 1 h latency. These episodes reached to peak after 2 h and persisted for 4 h. Pre-treatment of GTS (500 mg/kg, p.o.) significantly reduced cisplatin-induced nausea and vomiting by <TEX>$51\;\pm\;8.4\;and\;48.8\;\pm\;6.4\%$</TEX> during 4 h compared to GIS­untreated group, respectively. These results show the possibility that in vitro inhibition of <TEX>$5-HT_{3A}$</TEX> receptor channel activity by ginsenosides might be coupled to in vivo anti-emetic activity.