[논문]The Inhibitory Effects of Korean Red Ginseng Saponins on 5- HT3A Receptor Channel Activity Are Coupled to Anti-Nausea and Anti-Vomiting Action

Kim Jong-Hoon; Lee Byung-Hwan; Jeong Sang Min; Nah Seung-Yeol

doi:10.5142/jgr.2005.29.1.037

The Inhibitory Effects of Korean Red Ginseng Saponins on 5- HT3A Receptor Channel Activity Are Coupled to Anti-Nausea and Anti-Vomiting Action 원문보기

Journal of ginseng research = 高麗人參學會誌, v.29 no.1 = no.77, 2005년, pp.37 - 43

Kim Jong-Hoon (Research Laboratory for the Study of Ginseng Signal Transduction and Dept. of Physiology College of Veterinary Medicine, Konkuk University) , Lee Byung-Hwan (Research Laboratory for the Study of Ginseng Signal Transduction and Dept. of Physiology College of Veterinary Medicine, Konkuk University) , Jeong Sang Min (Research Laboratory for the Study of Ginseng Signal Transduction and Dept. of Physiology College of Veterinary Medicine, Konkuk University) , Nah Seung-Yeol (Research Laboratory for the Study of Ginseng Signal Transduction and Dept. of Physiology College of Veterinary Medicine, Konkuk University)

Abstract ▼ AI-Helper

We performed in vitro and in vivo studies to know whether the inhibitory effects of ginsenosides on $5-HT_{3A}$ 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 $5-HT_{3A}$ 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 $H_2O\;and\;5-HT_{3A}$ receptor cRNA. In oocytes injected with $5- HT_{3A}$ receptor cRNA, M4 treatment inhibited more potently 5-HT-induced inward peak current $(I_{5-HT})$ than CK with dose-dependent and reversible manner. The half-inhibitory concentrations $(IC_{50})$ of CK and M4 were $36.9\;\pm\;10.1\;and\;7.3\;\pm\;2.2\;{\mu}M$, respectively. The inhibition of $I_{5-HT}$ by M4 was non-competitive and voltage-independent. These results indicate that M4 might regulate $5-HT_{3A}$ 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 $51\;\pm\;8.4\;and\;48.8\;\pm\;6.4\%$ during 4 h compared to GISuntreated group, respectively. These results show the possibility that in vitro inhibition of $5-HT_{3A}$ receptor channel activity by ginsenosides might be coupled to in vivo anti-emetic activity.

주제어

AI 본문요약
AI-Helper

* AI 자동 식별 결과로 적합하지 않은 문장이 있을 수 있으니, 이용에 유의하시기 바랍니다.

가설 설정

Voltage-independent inhibition of I5 HT by M4. A. The representative current-voltage relationship was obtained using voltage ramps from -100 and +60 mV of 300-ms duration. Vbltage steps were applied before and after application of 10 μM 5-HT in the presence or absence of 100 μM CK or M4.
The cells were pretreated with M4 for 30s before 5-HT was applied. C. Summary of CK- or M4- induced inhibition of I5 Hr Holding potential was -80 mV. Tracings are representative of results with eighteen separate oocytes from three different frogs.
5 ㎎/㎏), we could observe cisplatin-induced emesis including nausea and vomiting"). As shown in Figures 5-7, cisplatin-induced nausea and vomiting episodes appeared after 60 min, reached to peak after 2 h, and persisted 니ntil 4 h. As a next step, we tested the effect of GTS on cisplatin-induced emesis. When we pre-administered GTS into cat with less than 250 ㎎/㎏ via oral route, we could not observe significant inhibitory effect of GTS on cisplatin (7.
). Number of nausea and vomting in the cat induced by a single dose of cisplatin was counted every 30 min intervals during 4 h. Results represent the mean + S.E.M. (*p v 0.01 compared with saline treatment alone, n = 7 - 8).
). Number of vomiting in the cat induced by a single dose of cisplatin was counted every 30 min intervals during 4 h. Results represent the mean ± S.E.M. (切 < 0.01 compared with saline treatment alone, n = 7 - 8).

데이터처리

n is the interaction coefficient. All values are presented as means ± S.E.M. The differences between means of control and CK or M4 treatment data were analyzed using unpaired Students t test. A value of P<0.

후속연구

This action may be also relevant to the in vivo anti-emetic effects observed in the present study. However, it is not yet determined exactly whether ginsenosides and their metabolites could penetrate blood-brain barrier and further studies will be needed to clarify the role of bloodbrain barrier in ginsenoside-induced anti-emetic efficacy.

참고문헌 (23)

Abe, T. : Clinical studies of the vitamins. Jpn. Soc. Inter. Med. 54, 989-1006 (1965)

상세보기
Attele, A. S., Wu, J. A. and Yuan, C. S. : Ginseng pharmacology: multiple onstituents and multiple actions. Biochem. Pharmacol. 58, 1685-1693 (1999)

상세보기
Kudo, K., Tachikawa, E., Kashimoto, T. and Takahashi, E. : Properties of ginseng saponin inhibition of catecholamine secretion in bovine chromaffin cells. Eur. J. Pharmacol. 341, 139-144 (1998)

상세보기
Choi, S., lung, S. Y., Lee, J. H., Sala, F., Criado, M., Mulet, J., Valor, L. M., Sala, S., Engel, A. G. and Nah, S. Y. : Effects of ginsenosides, active components of ginseng, on nicotinic acetylcholine receptors expressed in Xenopus oocytes. Eur. J. Pharmacol. 442, 37-45 (2002)

상세보기
Sala, F., Mulet, J., Choi, S., lung, S. Y., Nah, S. Y., Rhim, H., Valor, L. M., Criado, M. and Sala, S. : Effects of ginsenoside $Rg_2$ on human neuronal nicotinic acetylcholine receptors. J. Pharmacol. Exp. Ther. 301, 1052-1059 (2002)

상세보기
Karikura, M., Miyase, T, Tanizawa, H., Taniyawa, T. and Takino, Y. : Studies on absorption, distribution, excretion and metabolism of ginseng saponins. VII. Comparison of the decomposition modes of ginsenoside $Rb_1$ and $Rb_2$ in the digestive tract of rats. Chem. Pharm. Bull. 39, 400-404 (1991)

상세보기
Kanaoka, M., Akao, T. and Kobashi, K. : Metabolism of ginseng saponins, ginsenosides by human intestinal flora. J. Trad. Med. 11, 241-245 (1994)
Wakabayashi, C., Hasegawa, H., Murata, J. and Saiki, I. : In vivo antimetastatic action of ginseng protopanaxadiol saponins is based on their intestinal bacterial metabolites after oral administration. Oneol. Res. 9, 411-417 (1997)
Wakabayashi, C., Murakami, K, Hasegawa, H., Murata, J. and Saiki, I. : An intestinal bacterial metabolite of ginseng protopanaxadiol saponins has the ability to induce apoptosis in tumor cells. Biochem. Biophys. Res. Commun. 249, 725-730 (1998)
Ortells, M. O. and Lunt, G G : Evolutionary history of the ligand-gated on channel superfamily of receptors. Trends Neurosci. 18, 121-127 (1995)

상세보기
Jackson, M. B. and Yakel, J. L. : The 5- $HT_3$ receptor channel. Annu. Rev. Physiol. 57, 447-468 (1995)

상세보기
Lucot, J. B. : Blockade of 5- $hydroytryptamine_3$ receptors prevents cisplatin-induced but not motion- or xylazine-induced emesis in the cat. Pharmacol. Biochem. Behav. 32, 207-210 (1989)

상세보기
Schworer, H., Racke, K. and Kilbinger, H. : Cisplatin increases the release of 5-hydroxytryptamine (5-HT) from the isolated vascularly perfused small intestine of the guineapig-involvement of 5- $HT_3$ receptors. Naunyn-Schmiedeberg's Arch. Pharmacol. 344, 143-149 (1991)
King, G. L.: Animal models in the study of vomiting. Can. J. Physiol. Pharmacol. 68,260-268 (1990)

상세보기
Dang, H., England, P. M., Farivar, S. S., Dougherty, D. A. and Lester, H. A. : Probing the role of a conserved Ml proline residue in 5 $hydroytryptamine_3$ receptor gating. Mol. Pharmacol. 57, 1114-1122 (2000)

상세보기
Arias, H. R. : Luminal and non-luminal non-competitive inhibitor binding sites on the nicotinic acetylcholine receptor. Mol. Membr. Biol. 13, 1-17 (1996)

상세보기
Heidman, T, Oswald, R. E. and Changeux, J. P. : Multiple sites of action for noncompetitive blockers on acetylcholine receptor rich membrane fragments from Torpedo marmorata. Biochemistry 22, 3112-3127 (1983)

상세보기
Sine, S. M. and Taylor, P. : Local anesthetic and histrionicotoxin are allosteric inhibitors of the acetylcholine receptor. J. Biol. Chem. 257, 8106-8114 (1982)
Fortney, J. T, Gan, T. J., Graczyk, S., Wetchler, B., Melson, T., Kahlil, S., Mckenzie, R., Pamillo, S., Glass, P. S., Moote, C., Wermeling, D., Parasuraman, T. V., Duncan, B. and Creed, M. R. : A comparison of the efficacy, safety, and patient satisfaction of ondansetron versus droperidol as antiemetics for elective outpatient surgical procedures. S3A-409 and S3A-410 Study Groups. Anesth. Analg. 86, 731-738 (1998)

상세보기
Perez, E. A. and Gandara, D. R. : Advances in the control of chemotherapy-induced emesis. Ann. Oncol. 3 Suppl. 3, 47-50 (1992)
Polati, E., Verlato G., Finco, G., Monsaner, W., Grosso, S., Gottin, L., Pinaroli, A. M. and Ischia, S. : Ondansetron versus metoclopramide in the treatment of postoperative nausea and vomiting. Anesth. Analg. 85, 395-399 (1997)

상세보기
Chevallier, B. : The control of acute cisplatin-induced emesis a comparative study of granisetron and a combination regimen of high-dose metoclopramide and dexamethasone. Br. J. Cancer 68, 176-180 (1993)

상세보기
Lee, B.-H., Lee, J.-H., Jung, S.-M., Kim, D.-H., Kim, J.-H., Kim, J.-I., Lee, S.-M. and Na, S.-Y. : Differential Effect of Ginsenoside Metabolites on the 5- $HT_3A$ Receptor-Mediated Ion Current in Xenopus Oocytes. Mol. Cells, 17, 1, 51-56 (2004)

상세보기

내보내기 구분	파일저장 인쇄 메일전송
구성항목	기본정보 상세정보 관리번호, 논문명, 저널/프로시딩명, 저자 , 발행년, 권, 호, 시작페이지, 끝페이지, 발행기관 관리번호, 논문명, 대등논문명, 저자 , 저널/프로시딩명, 발행기관, 발행년, 발행언어, 권, 호, 시작페이지, 끝페이지, ISBN, ISSN, 주제분야, 키워드, 초록(한글), 초록(영문), 저자(소속기관)
저장형식	Text(ASCII format) Excel format RefWorks Direct Export RIS format (for Reference Manager, ProCite, EndNote), Scholar's Aids, Mendeley
메일정보	받는사람 (필수) @ 보내는사람 (선택) @ 제목 내용 KISTI 검색결과 이메일 서비스
안내	총 건의 자료가 검색되었습니다. 다운받으실 자료의 인덱스를 입력하세요. (1-10,000) 검색결과의 순서대로 최대 10,000건 까지 다운로드가 가능합니다. 데이타가 많을 경우 속도가 느려질 수 있습니다.(최대 2~3분 소요) 다운로드 파일은 UTF-8 형태로 저장됩니다. 파일의 내용이 제대로 보이지 않을실 때는 웹브라우저 상단의 보기 -> 인코딩 -> 자동선택 여부를 확인하십시오. ~ Text(ASCII format) Excel format

연합인증

The Inhibitory Effects of Korean Red Ginseng Saponins on 5- HT3A Receptor Channel Activity Are Coupled to Anti-Nausea and Anti-Vomiting Action 원문보기

Abstract ▼ AI-Helper

주제어

AI 본문요약
AI-Helper

가설 설정

데이터처리

후속연구

참고문헌 (23)

이 논문을 인용한 문헌

저자의 다른 논문 :

관련 콘텐츠

원문 보기

원문 URL 링크

오픈액세스(OA) 유형

이 논문과 함께 이용한 콘텐츠

AI-Helper ※ AI-Helper는 오픈소스 모델을 사용합니다.

선택된 텍스트

연합인증

The Inhibitory Effects of Korean Red Ginseng Saponins on 5- HT3A Receptor Channel Activity Are Coupled to Anti-Nausea and Anti-Vomiting Action 원문보기

Abstract ▼ AI-Helper

주제어

AI 본문요약 엑셀 다운로드 AI-Helper

가설 설정

데이터처리

후속연구

참고문헌 (23)

이 논문을 인용한 문헌

저자의 다른 논문 :

이병환 (27) 정상민 (9) 나승열 (58)

관련 콘텐츠

원문 보기

원문 URL 링크

오픈액세스(OA) 유형

이 논문과 함께 이용한 콘텐츠

AI-Helper ※ AI-Helper는 오픈소스 모델을 사용합니다.

선택된 텍스트

AI 본문요약
AI-Helper