Effect of Ginseng Saponins on a Rat Visceral Hypersensitivity Model

Abstract

One of the most common gastrointestinal disorders without 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 receptor 3 (5-HT 3 ). Zacopride, a 5-HT 3 -receptor antagonist, has been used to effectively treat diarrhea-predominant IBS patients with abdominal pain and bowel discomfort. 1) However, other 5-HT 3 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.2,3) These and other findings seem to indicate that the 5-HT 3 receptors are associated with the nociceptive processes of visceral pain in both humans and animals, 4) but the precise mechanisms by which 5-HT 3 -receptor antagonists inhibit the visceral pain remain unclear. Researchers are currently seeking to identify new 5-HT 3 -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.5) 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).6) 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 Rg 2 , potently inhibit acetylcholine-stimulated Na ϩ influx. 7) 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. 8,9) 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-HT 3A receptors to a greater degree than did PD ginsenosides and the PD ginsenoside metabolite, Compound K.10) Since 5-HT 3A receptors exist in enteric nervous systems and are involved in IBS, the observation that ginsenosides can block 5-HT 3A receptor channel activity suggests that ginsenosides might alleviate IBS. However, no previous work has examined whether t...

Ginseng ginsenoside pharmacology in the nervous system: involvement in the regulation of ion channels and receptors

“…Nausea and vomiting are significant adverse effects of anti-cancer agents such as cisplatin, and cause significant patient morbidity. 5-HT 3 receptors are involved in vomiting and irritable bowel syndrome (Kim et al, 2005a,b). Ginsenoside-mediated action of 5-HT 3A receptor channel activity may be the molecular basis of the anti-vomiting action of ginseng.…”

Use of Ginseng in Medicine With Emphasis on Neurodegenerative Disorders

“…It was further reported that the activity of natural killer cells and lymphocyte-activated killer cells was significantly increased in the peripheral blood of patients undergoing radiotherapy with simultaneous administration of ginseng polysaccharides compared to patients not receiving ginseng polysaccharides. Moreover, one of the future promising effects of ginseng is treatment of the irritable bowel syndrome (IBS) since it was shown that protopanaxatriol (PT) ginsenosides attenuated the experimentally-induced visceral hypersensitivity (130). Sparsely, ginseng has been reported to possess positive effects against herpes simplex type-II infections and diabetes mellitus, common cold symptom complex, ethanol-induced gastric lesion, and aspirin-induced gastric ulcers (131).…”

Daikenchuto significantly improves stool consistency and lower gastrointestinal symptoms in patients with chronic constipation

“…The success of DKT in the treatment of abdominal bloating in the present randomized controlled trial may be attributed to two interesting pharmacological effects reported in previous basic studies. The first is the improvement of GI motility via TRIPV1, TRIPA1, or motilin, 14,18,34 and the second is the possible improvement in visceral hypersensitivity due to its anti‐inflammatory effects 21 and antagonistic effects on 5‐HT 3A receptors in peripheral nerves 36 . Further study is necessary to clarify how these mechanisms of action of DKT affect abdominal bloating in humans.…”