Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Korean Red Ginseng Extract Activates Non-NMDA Glutamate and GABAA Receptors on the Substantia Gelatinosa Neurons of the Trigeminal Subnucleus Caudalis in Mice

  • Yin, Hua (Department of Oral Physiology, School of Dentistry and Institute of Oral Bioscience, Chonbuk National University) ;
  • Park, Seon-Ah (Department of Oral Physiology, School of Dentistry and Institute of Oral Bioscience, Chonbuk National University) ;
  • Park, Soo-Joung (Department of Oral Physiology, School of Dentistry and Institute of Oral Bioscience, Chonbuk National University) ;
  • Han, Seong-Kyu (Department of Oral Physiology, School of Dentistry and Institute of Oral Bioscience, Chonbuk National University)
  • Received : 2011.01.11
  • Accepted : 2011.05.19
  • Published : 2011.06.29
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Abstract

Korean red ginseng (KRG) is a valuable and important traditional medicine in East Asian countries and is currently used extensively for botanical products in the world. KRG has both stimulatory and inhibitory effects on the central nervous system (CNS) suggesting its complicated action mechanisms. The substantia gelatinosa (SG) neurons of the trigeminal subnucleus caudalis (Vc) are involved in orofacial nociceptive processing. Some studies reported that KRG has antinociceptive effects, but there are few reports of the functional studies of KRG on the SG neurons of the Vc. In this study, a whole cell patch clamp study was performed to examine the action mechanism of a KRG extract on the SG neurons of the Vc from juvenile mice. KRG induced short-lived and repeatable inward currents on all the SG neurons tested in the high chloride pipette solution. The KRG-induced inward currents were concentration dependent and were maintained in the presence of tetrodotoxin, a voltage gated $Na^+$ channel blocker. The KRG-induced inward currents were suppressed by 6-cyano-7-nitroquinoxaline-2,3-dione, a non-N-methyl-D-aspartate (NMDA) glutamate receptor antagonist and/or picrotoxin, a gamma-aminobutyric acid $(GABA)_A$ receptor antagonist. However, the inward currents were not suppressed by d,l-2-amino-5-phosphonopentanoic acid, an NMDA receptor antagonist. These results show that KRG has excitatory effects on the SG neurons of the Vc via the activation of non-NMDA glutamate receptor as well as an inhibitory effect by activation of the $GABA_A$ receptor, indicating the KRG has both stimulatory and inhibitory effects on the CNS. In addition, KRG may be a potential target for modulating orofacial pain processing.

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References

  1. Attele AS, Wu JA, Yuan CS. Ginseng pharmacology: multiple constituents and multiple actions. Biochem Pharmacol 1999;58:1685-1693. https://doi.org/10.1016/S0006-2952(99)00212-9
  2. Tachikawa E, Kudo K, Harada K, Kashimoto T, Miyate Y, Kakizaki A, Takahashi E. Effects of ginseng saponins on responses induced by various receptor stimuli. Eur J Pharmacol 1999;369:23-32. https://doi.org/10.1016/S0014-2999(99)00043-6
  3. Yun TK. Brief introduction of Panax ginseng C.A. Meyer. J Korean Med Sci 2001;16 Suppl:S3-S5.
  4. Han BH, Park MH, Han YN. Studies on the anti-oxidant components of Korean ginseng. In: Korea Ginseng Research Institute. Proceedings of Second International Ginseng Symposium; Seoul, Korea, 1978;13-17.
  5. Jin SH, Park JK, Nam KY, Park SN, Jung NP. Korean red ginseng saponins with low ratios of protopanaxadiol and protopanaxatriol saponin improve scopolamine-induced learning disability and spatial working memory in mice. J Ethnopharmacol 1999;66:123-129. https://doi.org/10.1016/S0378-8741(98)00190-1
  6. Jeon BH, Kim CS, Kim HS, Park JB, Nam KY, Chang SJ. Effect of Korean red ginseng on blood pressure and nitric oxide production. Acta Pharmacol Sin 2000;21:1095-1100.
  7. Surh YJ, Ferguson LR. Dietary and medicinal antimutagens and anticarcinogens: molecular mechanisms and chemopreventive potential-highlights of a symposium. Mutat Res 2003;523-524:1-8.
  8. Kaneko H, Nakanishi K. Proof of the mysterious efficacy of ginseng: basic and clinical trials. Clinical effects of medical ginseng, Korean red ginseng: specifically, its anti-stress action for prevention of disease. J Pharmacol Sci 2004;95:158-162. https://doi.org/10.1254/jphs.FMJ04001X5
  9. Vuksan V, Sung MK, Sievenpiper JL, Stavro PM, Jenkins AL, Di Buono M, Lee KS, Leiter LA, Nam KY, Arnason JT et al. Korean red ginseng (Panax ginseng) improves glucose and insulin regulation in well-controlled, type 2 diabetes: results of a randomized, double-blind, placebo-controlled study of efficacy and safety. Nutr Metab Cardiovasc Dis 2008;18:46-56. https://doi.org/10.1016/j.numecd.2006.04.003
  10. Choi HK, Seong DH, Rha KH. Clinical efficacy of Korean red ginseng for erectile dysfunction. Int J Impot Res 1995;7:181-186.
  11. De Andrade E, de Mesquita AA, Claro Jde A, de Andrade PM, Ortiz V, Paranhos M, Srougi M. Study of the efficacy of Korean red ginseng in the treatment of erectile dysfunction. Asian J Androl 2007;9:241-244. https://doi.org/10.1111/j.1745-7262.2007.00210.x
  12. Sessle BJ. Mechanisms of trigeminal and occipital pain. Pain Rev 1996;3:91-116.
  13. Gobel S, Falls WM, Bennett GJ, Abdelmoumene M, Hayashi H, Humphrey E. An EM analysis of the synaptic connections of horseradish peroxidase-filled stalked cells and islet cells in the substantia gelatinosa of adult cat spinal cord. J Comp Neurol 1980;194:781-807. https://doi.org/10.1002/cne.901940406
  14. Kumazawa T, Perl ER. Excitation of marginal and substantia gelatinosa neurons in the primate spinal cord: indications of their place in dorsal horn functional organization. J Comp Neurol 1978;177:417-434. https://doi.org/10.1002/cne.901770305
  15. Light AR, Perl ER. Reexamination of the dorsal root projection to the spinal dorsal horn including observations on the differential termination of coarse and fine fibers. J Comp Neurol 1979;186:117-131. https://doi.org/10.1002/cne.901860202
  16. Light AR, Kavookjian AM. Morphology and ultrastructure of physiologically identified substantia gelatinosa (lamina II) neurons with axons that terminate in deeper dorsal horn laminae (III-V). J Comp Neurol 1988;267:172-189. https://doi.org/10.1002/cne.902670203
  17. Pan YZ, Pan HL. Primary afferent stimulation differentially potentiates excitatory and inhibitory inputs to spinal lamina II outer and inner neurons. J Neurophysiol 2004;91:2413-2421. https://doi.org/10.1152/jn.01242.2003
  18. Bhargava HN, Ramarao P. The effect of Panax ginseng on the development of� �tolerance to the pharmacological actions of morphine in the rat. Gen Pharmacol 1991;22:521-525. https://doi.org/10.1016/0306-3623(91)90017-Z
  19. Sampson JH, Phillipson JD, Bowery NG, O'Neill MJ, Houston JG, Lewis JA. Ethnomedicinally selected plants as sources of potential analgesic compounds: indication of in vitro biological activity in receptor binding assays. Phytother Res 2000;14:24-29. https://doi.org/10.1002/(SICI)1099-1573(200002)14:1<24::AID-PTR537>3.0.CO;2-9
  20. Lee JH, Lee JH, Lee YM, Kim PN, Jeong CS. Potential analgesic and anti-inflammatory activities of Panax ginseng head butanolic fraction in animals. Food Chem Toxicol 2008;46:3749-3752. https://doi.org/10.1016/j.fct.2008.09.055
  21. Choi SE, Choi S, Lee JH, Whiting PJ, Lee SM, Nah SY. Effects of ginsenosides on GABA(A) receptor channels expressed in Xenopus oocytes. Arch Pharm Res 2003; 26:28-33. https://doi.org/10.1007/BF03179927
  22. Kim S, Ahn K, Oh TH, Nah SY, Rhim H. Inhibitory effect of ginsenosides on NMDA receptor-mediated signals in rat hippocampal neurons. Biochem Biophys Res Commun 2002;296:247-254. https://doi.org/10.1016/S0006-291X(02)00870-7
  23. Lee E, Kim S, Chung KC, Choo MK, Kim DH, Nam G, Rhim H. 20(S)-ginsenoside Rh2, a newly identified active ingredient of ginseng, inhibits NMDA receptors in cultured rat hippocampal neurons. Eur J Pharmacol 2006;536:69-77. https://doi.org/10.1016/j.ejphar.2006.02.038
  24. Huang KC. The pharmacology of Chinese herbs. Boca Raton: CRC Press, 1999.
  25. Gillis CN. Panax ginseng pharmacology: a nitric oxide link? Biochem Pharmacol 1997;54:1-8. https://doi.org/10.1016/S0006-2952(97)00193-7
  26. Yuan CS, Attele AS, Wu JA, Liu D. Modulation of American ginseng on brainstem GABAergic effects in rats. J Ethnopharmacol 1998;62:215-222. https://doi.org/10.1016/S0378-8741(98)00066-X
  27. Johnston GA. $GABA_A$ receptor pharmacology. Pharmacol Ther 1996;69:173-198. https://doi.org/10.1016/0163-7258(95)02043-8
  28. Kim YC, Kim SR, Markelonis GJ, Oh TH. Ginsenosides $Rb_1$ and $Rg_3$ protect cultured rat cortical cells from glutamate-induced neurodegeneration. J Neurosci Res 1998; 53:426-432. https://doi.org/10.1002/(SICI)1097-4547(19980815)53:4<426::AID-JNR4>3.0.CO;2-8
  29. Shi W, Wang Y, Li J, Zhang HQ, Ding L. Investigation of ginsenosides in different parts and ages of Panax ginseng. Food Chem 2007;102:664-668. https://doi.org/10.1016/j.foodchem.2006.05.053

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