Anti-stress Effect of Scutellatia baicalensis in SD Rats and ICR Mice

Ryu, Jong-Hoon;Tan-Lee, Blendyl Saguan;Jung, Ji-Woong;Ahn, Nam-Yoon;Lee, Seung-Joo;Yu, Gu-Young;Han, Shin-Ha;Lee, Jeong-Hoon;Lee, Geum-Seon;Cheong, Jae-Hoon

  • Published : 2004.03.01


The aim of this study is to investigate anti-stress effect of Scutellaria baicalensis(SB). The experiments were performed with the use of young (9 weeks of age) male rats of SD strain and the male ICR mice (20-25 g) at the time of first treatment with SB. Animals of the normal group were not exposed to any stress and the control group were exposed to stress. The rats of the Ginseng, Diazepam(BZ) and SB supplementary group were orally administered once a day 100 mg of red ginseng extract, 5 mg of BZ or 100 mg of SB extract/kg body weight and they were exposed to stress. The mice of the Ginseng, BZ and SB supplementary group were given water containing 200 mg of red ginseng extract, 10 mg of BZ or SB extract/100 ml potable water and exposed to stress. Animals were given supplements for 7 days without stress, and then were given supplement for 5 days with restraining and electroshock stress. We recorded stress related behavioral changes of the experimental animals by stressing them using the Etho-vision system and measured levels of blood corticosterone and IL-2. SB supplementation partially blocked the stress effect on locomotion in the rats and mice, and also partially blocked stress-induced behavioral changes such as freezing, burrowing, grooming, smelling, and rearing behavior in the rats and smelling, grooming, tailing, and rearing in the mice. in elevated plus maze test, the staying time of the stressed rats and mice in the open area decreased while it increased in the closed area. But these changes also partially were blocked by SB-supplementation. SB-supplementation decreased levels of the blood corticosterone which was increased by stress in the rats but did not significantly increase levels of blood interleukin 2 which was decreased by stress in mice.


Scutellaria baicalensis;Stress;Behavior;Corticosterone;Interleukin-2


  1. Ai, A.L. and Bolling, S.F. (2002) The use of complementary and alternative therapies among middle-aged and older cardiac patients. Am. l. Med. Qual. 17,21-27
  2. Armario, A., Restrepo, C., Castellanos, J.M. and Balasch, J. (1985) Dissociation between adrenocorticotropin and corticosterone responses to restraint after previous chronic exposure to stress. Life Sci. 36, 2085-2092
  3. Barnard, 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
  4. Barsky, A.J. Wyshak, G. and Klerman, G.L. (1986) Medical and psychiatric determinants of outpatient medical utilization. Med. Care 24, 548-560
  5. Beck, C.H. and Fibiger, H.C. (1995) Conditioned fear-induced changes in behavior and in the expression of the immediate early gene c-fos: with and without diazepam pretreatment. J. Neurosci. 15, 709-720
  6. Blazer, D., Hughes, D. and George, L.K. (1987) Stress Life Events and the Onset of a Generalized Anxiety Syndrome. Am. J. Psychiatry 144, 9-18
  7. Breier, A., Albus, M., Picker, D., Zahn, T.P., Wolkowitz, O.M. and Paul, S.M. (1987) Controllable and Uncontrollable Stress in Humans: Alterations in Mood and Neuroendocrine and Psychophysiological Function. Am. J. Psychiatry 144, 11-19
  8. Cantrell, D.A. and Smith, K.A. (1984) The interleukin 2 T cell system: a new cell growth model. Science 224,1312-1316
  9. Choi, S.S., Lee, J.K. and Suh, H.W. (2003) Effect of Ginsenosides Administered Intrathecally on the Antinocieption Induced by Cold Water Swimming Stress in the Mouse. Biol. Pharm. Bull. 26, 858-861
  10. Chrousos, G.P. and Gold, P.W. (1992) The concepts of stress and stress system disorders. Overview of physical and behavioral homeostasis. JAMA 267, 1244-1252
  11. 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
  12. Dimsdale, J.E., Keefe, H.J. and Stein, M.B. (2000) Stress and pyschiatry. In Comprehensive textbook of psychiatry. Vol 2, 7th ed. Ed by Sadock B.1., Sadock V.A., Philadelphia, USA, pp. 1835-46
  13. Djordjevic, J., Cvijic, G. and Davidovic, V. (2002) Different Activation of ACTH and Corticosterone Release in Response to Various Stressors in Rats. Physiol. Res. 52, 67-72
  14. Fanselow, M.S. (1980) Conditional and unconditional components of post-shock freezing. Pavlov. J. Bioi. Sci. 15, 177-182
  15. Felton, S.Y. and Olschowka, J. (1987) Noradrenergic sympathetic innervation of the spleen, II: tyrosine hydroxylase (TH)-posItIve nerve tenninals from synaptic-like contacts on lymphocytes in the splenic white pulp. J. Neurosci. Res. 18, 37-48
  16. 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
  17. Finlay, J.M., Zigmond, M.J. and Abercrombie, E.D. (1995) Increased dopamine and norepinephrine release in medial prefrontal cortex induced by acute and chronic stress: effects of diazepam. Neuroscience 64, 619-628
  18. Glaser, R., Kennedy, S., Lafuse, W.P., Bonneau, R.H., Speicher, C., Hillhouse. J. and Kiecolt-Glaser, J.K. (1990) Psychological Stress-Induced Modulation of Interleukin 2 Receptor Gene Expression and Interleukin 2 Production in Peripheral Blood Leukocytes. Arch. Gen. Psychiatry 47, 707-712
  19. Glass, D.C. (1977) Stress, Behavior Patterns, and Coronary Disease. Am Scientist 65, 177-187
  20. Harikai, N., Tomogane, K., Miyamoto, M., Shimada, K., Onodera, S. and Tashiro, S. Dynamic Responses to Acute Heat Stress Between 34 C and 38.5 C, and Characteristics of Heat Stress Response in Mice. Biol. Pharm. Bull. 26, 701-708
  21. 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. Biochemical Pharmacology 64, 1415-1424
  22. Hui, K.M., Wang, X.H. and Xue, H. (2000) Interaction of flavones from the roots of Scutellaria baicalensis with the benzodiazepine site. Planta Med. 66, 91-93
  23. Hurst, M.W., Jenkins, C.D. and Rose, R.M. (1976) The Relation of psychological stress to onset of medical illness. Ann. Rev. Med. 27,301-312
  24. Ida, Y., Tanaka, M., Tsuda, A., Tsujimaru, S. and Nagasaki, N. (1985) Attenuating effect of diazepam on stress-induced increases in noradrenaline turnover in specific brain regions of rats: antagonism by Ro 15-1788. Life Sci. 37,2491-2498
  25. Kaneko, H., Nakanishi, K., Murakami, A., Kaidoh, H. and Kuwashima, K. (1996) The acute effects of massive dose of red ginseng on healthy adults under the condition of cold stress. Ginseng Review 22, 20-24
  26. Kim, D.H., Jung, J.S., Moon, Y.S., Sung, J.H., Suh, H.W., Kim, Y.H. and Song, D.K. (2003d) Inhibition of Intracerbroven-tricular Injection Stress-Induced Plasma Corticosterone Levels by Intracerebroventricularly Administered Compound K, a Ginseng Saponin Metabolite, in Mice. Biol. Pharm. Bull. 26, 10351038
  27. Kim, D.H., Moon, Y.S., Jung, J.S., Min, S.K., Son, B.K., Suh, H.W. and Song, D.K. (2003a) Effects of Ginseng saponin administered intraperitoneally on the hypothalamo-pituitaryadrenal axis in mice. Neuroscience Letters 343, 62-66
  28. Kim, K.M., Kwon, Y.G., Chung, H.T., Yun, Y.G., Pae, H.O., Han, J.A., Ha, K.S., Kim, T.W. and Kim, Y.M. (2003c) Methanol extract of Cordyceps pruinosa inhibits in vitro and in vivo inflammatory mediators by suppressing NF-KB activation. Toxicol. Appl. Pharmacol. 190, 1-8
  29. 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. (2003b) Anti-stress effect of Pyroligneous liquid in SD rats and ICR mice. J. Appl. Pharmacol. 11, 249-256
  30. Koh, K.B. and Lee, B.K. (1998) Reduced Lymphocyte Prolifera-tion and Interleukin-2 Production in Anxiety Disorders. Psychosomatic Med. 60,479-483
  31. Lin, C.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
  32. Miksicek, R.J. (1993) Commonly occurring plant flavonoids have estrogenic activity. Mol. Pharmacol. 44,37-43
  33. Munck, A., Guyre, P.M. and Holbrook, N.J. (1984) Physiological functions of glucocorticoids in stress and their pharmacological actions. Endocrine Rev. 51, 25-44
  34. Noldus, L.P.J.J., Spink, A.J. and Tegelenbosch, A.J. (2001) EthoVision: A versatile video tracking system for automation of behavioral experiments. Psychonomic Society 33, 398-414
  35. 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, 125129
  36. 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
  37. Park, I., Kim, Y.I, Lee, S.M. and Cho, T.S. (1996) Anti-stress effect of cholic acid derivatives in restraint stress induced rats. J. Appl. Pharmacol. 4, 162-166
  38. Petrowicz, O., Gebhardt, R., Donner, M., Schwandt, P. and Kraft, K. (1997) Effects of artichoke leaf extract (ALE) on lipoprotein metabolism in vitro and in vivo. Atherosclerosis 129, 147-156
  39. 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
  40. Selye, H. (1993) History of the stress concept. In: Handbook of Stress, Ed by Goldberg L, Brenitz S, New York, USA The Free Press, pp. 7-36
  41. Takeuchi, T., Iwanaga, M. and Harada, E. (2003) Possible regulatory mechanism of DHA-induced anti-stress reaction in rats. Brain Res. 964, 136-143
  42. Thirugnanasambantham, P., Viswanathan, S., Ramaswamy, S., Krishnamurty, V. Mythirayee, C. and Kameswaran L. (1992) Analgesic activity of certain flavone derivatives: a structureactivity study. Clin. Exp. Pharmacol. Physiol. 20, 59-63
  43. Ward, C.P, Rsdd, K., Williams, B.M., Caler, J.R, Luo, Y. and McCoy, J.G. (2002) Ginkgo bioloba extract: Cognitive enhancer or anti-stress buffer. Pharmacol. Boichem. Behav. 72, 913-922
  44. Wolfman, C., Viola, H., Paladini, A., Dajas, F. and Medina, J.H. (1994) Possible anxiolytic effects of chrysin, a central benzodiazepine receptor ligand isolated from Passiflora coerulea. Pharmacol. Biochem. Behav. 47, 1-4
  45. Yuan, W.X., Wu, X.J., Yang, E.X., Shang, X.H. and Zhang, L.L. (1989) Effects of Ginseng root saponins on brain monoamines and serum corticosterone in heat-stressed mice. Zhongguo Yao Li Hsueh Pao Mar 10, 492-6
  46. Zhu, Y.P. (1998) Chinese Materia Medica: chemistry, phannacology, and applications. The Netherlands: Harward Academic