Biol. Pharm. Bull. 28(11) 2120—2124 (2005)

out direct bacterial or viral infection is irritable bowel syndrome (IBS), which is strongly associated with stress. The most common IBS symptoms are abnormal visceral discomfort, pain and diarrhea. Although the precise mechanism of IBS has not been fully elucidated, some symptoms of IBS are thought to involve the 5-hydroxytryptamine receptor3 (5HT3). Zacopride, a 5-HT3-receptor antagonist, has been used to effectively treat diarrhea-predominant IBS patients with abdominal pain and bowel discomfort. However, other 5HT3 receptor antagonists have demonstrated a wide heterogeneity of potency and efficacy against visceral pain; granisetron reduces rectal sensitivity in IBS patients, but ondansetron does not. These and other findings seem to indicate that the 5-HT3 receptors are associated with the nociceptive processes of visceral pain in both humans and animals, but the precise mechanisms by which 5-HT3-receptor antagonists inhibit the visceral pain remain unclear. Researchers are currently seeking to identify new 5-HT3-receptor antagonists capable of blocking abnormal visceral perception without deleterious side effects. Ginseng, the root of Panax ginseng C. A. MEYER, is well known for restoring and promoting human health. In traditional medicine, ginseng has been used as an antidote for stress and to alleviate disorders such as anorexia, dyspepsia, pain and vomiting. The main molecular components responsible for the actions of Panax ginseng are the ginsenosides, which are also known as ginseng saponins. Approximately 30 different ginsenoside forms have been isolated and identified from the root of Panax ginseng. These molecules have a four-ring, steroid-like structure bearing sugar moieties, and can be classified into protopanaxadiol (PD) or protopanaxatriol (PT) ginsenosides according to the position of the sugar moieties at carbon-3 or -6 (Fig. 1). Ginsenosides regulate several types of ligand-gated ion channel activity, and differential regulation is seen by the PT and PD forms. In cells expressing nicotinic acetylcholine receptors, such as bovine chromaffin cells, the PT ginsenosides, especially ginsenosides Rf and Rg2, potently inhibit acetylcholine-stimulated Na influx. Choi et al. (2002) and Sala et al. (2002) showed that PT ginsenosides potently inhibited acetylcholine-induced inward currents in Xenopus oocytes expressing several subtypes of neuronal and muscle-type nicotinic acetylcholine receptors. Lee et al. (2004) showed that PT ginsenosides and the PT ginsenoside metabolite, M4, inhibited 5-HT-mediated inward currents in Xenopus oocytes expressing 5-HT3A receptors to a greater degree than did PD ginsenosides and the PD ginsenoside metabolite, Compound K. Since 5-HT3A receptors exist in enteric nervous systems and are involved in IBS, the observation that ginsenosides can block 5-HT3A receptor channel activity suggests that ginsenosides might alleviate IBS. However, no previous work has examined whether the regulation of 5-HT3A receptor channel activity by ginsenosides is coupled to attenuation of IBS. Here, we investigated whether the inhibitory effects of ginsenosides on 5-HT3A receptor channel activity are coupled to the alleviation of visceral hypersensitivity in vivo. We induced experimental visceral hypersensitivity by colorectal distention (CRD) and intracolonic infusion of 0.6% acetic acid (CRD-acetic acid) in rats, and examined the effect of ginsenosides (GTS, PT or PD) on CRD-acetic acid-induced visceral hypersensitivity as compared to the effect of zacopride, a known 5-HT3 receptor antagonist. We found that ginsenosides dose-dependently reduced CRD-acetic acid-induced visceral hypersensitivity, with the PT ginsenosides showing a more significant effect than the PD ginsenosides. 2120 Biol. Pharm. Bull. 28(11) 2120—2124 (2005) Vol. 28, No. 11