Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Different Effects of Flavonoids in Scutellaria baicalensis on Anxious and Sedative Behaviors

  • Park Hyung-Geun (Department of Pharmacy, Sahmyook University) ;
  • Choi Ji-Young (Department of Pharmacy, Sahmyook University) ;
  • Lee Geum-Seon (Department of Pharmacy, Sahmyook University) ;
  • Choi Jong-Hyun (Department of Pharmacy, Sahmyook University) ;
  • Son Kun-Ho (Department of Food Science and Nutrition, Andong National University) ;
  • Yoon Seo-Young (Department of Pharmacy, Sahmyook University) ;
  • Ko Hong-Sook (Department of Pharmacy, Sahmyook University) ;
  • Ko Kwang-Ho (Department of Pharmacology, College of Pharmacy, Seoul National University) ;
  • Ryu Jong-Hoon (Department of Oriental Pharmaceutical Science, College of Pharmacy, KyungHee University) ;
  • Cheong Jae-Hoon
  • Published : 2006.06.01
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Abstract

The main aim of this study was to characterize the pharmacological profile of flavonoids utilizing behavioral tests and to investigate how the psychopharmacological activities of wogonin, baicalein and oroxylin A are different. Wogonin, baicalein and oroxylin A were intraperitoneally injected as dosages of 2.5, 5, 10 and 20 mg/kg. In the locomotor activity, Rota-rod test, and elevated plus-maze tests, the behavioral parameters were analyzed by automatic systems. Thiopental induced sleeping time was measured. Water extract of S. baicalensis didn't exhibit sedative effect. Wogonin and bacalein exhibited anxiolytic activity although it was less potent than buspirone. Wogonin and baicalein decreased locomotor activity at a dose of 10 mg/kg. Wogonin also shortened significantly running time on the rota-rod at doses of 5 and 10 mg/kg. Wogonin and baicalein enhanced sleeping at doses of 5 and 10 mg/kg. These results indicate that wogonin produce anxiolysis with sedation and so did bacalein with mild sedation. On the contrary, oroxylin A enhanced running activity on the rotarod and did't depress locomotor activity. Oroxylin A significantly hindered sleeping rather than helped it at doses of 5 and 10 mg/kg. Oroxylin A didn't produce anxiolysis and instead, produce awakening effect. This study demonstrates that wogonin and bacalein exhibited anxiolytic activity with mild sedation, but oroxylin A didn't produce anxiolysis and instead, produce awakening effect. This result indicates that anxiolytic effect without sedation induced by Scutellaria baicalensis is produced by combination of flavonoids.

Keywords

References

  1. Bamard, L., Smee, M., Huffman, J.H., Meyerson, L.H. and Sidwell, R.W. (1993) Antiherpes virus activity of 59-303, a novel plant flavonoid. Chemotherapy 39, 203-211 https://doi.org/10.1159/000239127
  2. Cushman, M., Nagarathnam, D., Burg, D.L. and Geahlen, R.L. (1991) Synthesis and protein-tyrosine kinase inhibitory activities of flavonoid analogues. J. Med. Chem. 34, 798-806 https://doi.org/10.1021/jm00106a047
  3. Dekermendjian, K., Kahnberg, P., Witt, M.R., Sterner, O., Nielsen, M., and Liljefors, T. (1999) Structure?activity relationships and molecular modeling analysis of flavonoids binding to the benzodiazepine site of the rat brain GABA(A) receptor complex. J. Med. Chem. 42, 4343-4350 https://doi.org/10.1021/jm991010h
  4. Farkas, S., Berzsenyi, P., Karpati, E., Kocsis, P. and Tamawa, I. (2005) Simple pharmacological test battery to assess efficacy and side effect profile of cenlrally acting muscle relaxant drugs. J. Pharmacol. Toxicol. Methods 52, 264-273 https://doi.org/10.1016/j.vascn.2004.11.005
  5. Ferriola, P.C., Coy, V. and Middleton, E. (1989) Protein kinase C inhibition by flavonoids: kinetic mechanisms and structureactivity relationships. Biochem. Pharmacol. 38, 345-354
  6. Gardner, C.R., Tully, W.R. and Hedgecock, C.J.R. (1993) The rapidly expanding range of neuronal benzodiazepine receptor ligands. Prog. Neurobiol. 40, 1-61 https://doi.org/10.1016/0301-0082(93)90047-V
  7. Hui, K.M., Michael, S.Y., Huen, H.Y.W., Zheng, H., Sigel, E., Baur, R., Ren, H., Li, Z.W., Wong, J.T.F. and Xue, H. (2002) Anxiolytic effect of wogonin, a benzodiazepine receptor ligand isolated from Scutellaria baicalensis Georgi. Biochem. Pharmacol. 64, 1415-1424 https://doi.org/10.1016/S0006-2952(02)01347-3
  8. Hui, K.M., Wang, X.H. and Xue, H. (2000) Interaction of flavones from the roots of Scutellruia baicalensis with the benzodiazepine site. Planta Med. 66, 91-93
  9. Jeong, J.O., An, N.Y., Park, S.H., Oh, J.G., Oh, H. L., Lee, B.G., Om, A. S., Kim, B.S., Kim, D.H., Ryu, J. H. (2004) The Anxiolytic- like Effects of Scutellaria baicalensis Using Elevated Plus-Maze in Rats. Kor. J. Phannacogn. 35, 22-27
  10. Kim, M.K., Yu, G.Y., Tan-Lee, B.S., Oh, H.J., Dong, K.W/, Jeong, S.H., Han, S.W. and Cheong, J.H. (2003) Anti-stress effect of Pyroligneous liquid in SD rats and ICR mice. J. Appl. Pharmacol. 11, 249-256
  11. Lee, G.S. Choi, J.Y., Ko, H.S., Tan-Lee, B.S., Yu, G.Y., Park, H.G. Kim, M. K., Ryu, J.H., Jung, I.K. and Cheong, J.H. (2006) Stress-reducing Effects of Brown Rice Koji. Food Sci. Biotech. 15, 63-69
  12. Lin, C. and Shieh, D.E. (1996) The anti-inflammatory activity of Scutellaria rivularis extracts and its active components, baicalin, baicalein and wogonin. Am. J. Chin. Med. 24,31-36 https://doi.org/10.1142/S0192415X96000050
  13. Louis, C., Cohen, C., Depoortere, R., and Griebel, G. (2006) Antidepressant-Like Effects of the Corticotropin-Releasing Factor 1 Receptor Antagonist, SSR125543, and the Vasopressin Ib Receptor Antagonist, SSR149415, in a DRL-72 s Schedule in the Rat. Neuropsychopharmacology (advance online publication) 1, doi:10.1038/sj.npp.1301036
  14. Ma, S., Du, J., But, P., Deng, X., Zhang, Y., Ooi, V., Xu, H., Lee, S. and Lee, S. (2002) Antiviral Chinese medicinal herbs against respiratory syncytial virus. J. Ethnopharmacol. 792, 205-211
  15. Michael, S.Y.H., Justin W.C.L., Wah, Ng., Lui, W.S., Michelle, N.S.C., Wong, J.T. and Xue, H. (2003) 5,7-Dihydroxy-6-meth-oxyflavone, a benzodiazepine site ligand isolated from Scutellaria baicalensis Georgi, with selective antagonistic properties. Biochem. Pharmacol. 66, 125-132 https://doi.org/10.1016/S0006-2952(03)00233-8
  16. Miksicek, R.J. (1993) Commonly occurring plant flavonoids have estrogenic activity. Mol. Pharmacol. 44, 37-43
  17. Noldus, L.P.J.J., Spink, AJ. and Tegelenbosch, AJ. (2001) Etho-Vision: A versatile video tracking system for automation of behavioral experiments. Psychonomic Society 33, 398-414
  18. Oyama, Y., Fuchs, P.A., Katayama, N. and Noda, K. (1994) Myricetin and quercetin, the flavonoid constituents of Ginkgo biloba extract, greatly reduce oxidative metabolism in both resting and Ca2+ -loaded brain neurons. Brain Res. 635, 125-129 https://doi.org/10.1016/0006-8993(94)91431-1
  19. Paladini, A.C., Marder, M., Viola, H., Wolfman, C., Wasowski, C. and Medina, J.H. (1999) Flavonoids and central nervous system: from forgotten factors to potent anxiolytic compounds. J. Pharm. Pharmacol. 51,519-526 https://doi.org/10.1211/0022357991772790
  20. Ryu, J.H., Tan-Lee, B.G., Jung, J.W., Ahh, N.Y., Lee, S., Yu, G.Y., Han, S., Lee, J.H., Lee, G.S. and Cheong, J.H. (2004) Antistress Effect of Scutellaria baicalensis in SD Rats and ICR Mice. J. Appl. Pharmacol. 12, 34-42
  21. Salgueiro, J.B., Ardenghi, P., Dias, M., Ferreira, M.B.C., Izquierdo, I. and Medina, J.H. (1997) Anxiolytic natural and synthetic flavonoid ligands of the central benzodiazepine receptor have no effect on memory tasks in rat. Pharmacol. Biochem. Behav. 58, 887-891 https://doi.org/10.1016/S0091-3057(97)00054-3
  22. Shang, Y., Cheng, J., Qi, J. and Miao, H. (2005) Scutellaria flavonoid reduced memory dysfunction and neuronal injury caused by permanent global ischemia in rats Pharmacol. Biochem. Behav. 82, 67-73 https://doi.org/10.1016/j.pbb.2005.06.018
  23. Shang, Y., Miao, H., Cheng, J. and Qi, J. (2006) Effects of Amelioration of Total Flavonoids from Stems and Leaves of Scutellaria baicalensis Georgi on Cognitive Deficits, Neuronal Damage and Free Radicals Disorder Induced by Cerebral Ischemia in Rats. Biol. Pharmaceutical Bul. 29, 805-810 https://doi.org/10.1248/bpb.29.805
  24. Shieh, D.E., Liu, L. and Lin, C. (2000) Antioxidant and free radical scavenging effects of baicalein, baicalin and wogonin. Anticancer Res. 20, 2861-2865
  25. Wakabayashi, I. and Yasui, K. (2000) Wogonin inhibits inducible prostaglandin E(2) production in macrophages. Eur. J. Pharmacol. 406,477-481 https://doi.org/10.1016/S0014-2999(00)00695-6
  26. Wang, Q., Han, Y. and Xue, H. (1999) Ligands of GABAA receptor benzodiazepine binding site. CNS Drug Rev. 5, 125-144 https://doi.org/10.1111/j.1527-3458.1999.tb00094.x
  27. Zhu, Y.P. (1998) Chinese Materia Medica: chemistry, pharmacology, and applications. Harward Academic press., The Netherlands