DOI QR코드

DOI QR Code

Effect of Glycyrrhizae Radix Water Extract on the depression induced by LPS in Rats

LPS로 유발된 우울증에 대한 감초(甘草)의 효과

  • Ko, Sung-Youl (Department of Formulae Pharmacology, School of Oriental Medicine, Gachon University) ;
  • Kim, Do-Hoon (Department of Oriental Medical Classics & History, Gachon University) ;
  • Lee, Tae-Hee (Department of Formulae Pharmacology, School of Oriental Medicine, Gachon University)
  • 고성렬 (가천대학교 한의과대학 방제학교실) ;
  • 김도훈 (가천대학교 한의과대학 원전의사학교실) ;
  • 이태희 (가천대학교 한의과대학 방제학교실)
  • Received : 2014.05.09
  • Accepted : 2014.09.11
  • Published : 2014.09.30

Abstract

Objectives : Investigation of the antidepressant effect of Glycyrrhizae Radix (GR) through the anti-inflammatory effect. Methods : Depression in rats was induced by LPS (i,p.3days). The rats were treated with GR100 mg/kg (GR 100) or GR400 mg/kg (GR 400). The depressive immobility was examined with Tail Suspension Test(TST) and Forced Swimming Test(FST). The expression of nuclear factor-${\kappa}B$(NF-${\kappa}B)$, $I{\kappa}B$ was measured with western blotting. The concentration of corticosterone, cytokine in plasma was measured with ELISA. The expression of c-Fos in the paraventricular nucleus(PVN) and tyrosine hydroxylase(TH) in the locus coeluleus(LC) were measured with immunostaining method. Results : In the TST, GR400 group significantly decreased immobility time compared with the LPS group. In the FST, GR100, GR400 group significantly decreased immobility time comparing with the LPS group. c-Fos expression in GR100 and GR400 group was decreased comparing with the lipoplysaccharide(LPS) group. The $I{\kappa}B$ expression of GR100 and GR400 group was increased comparing with the LPS group. The level of corticosterone of GR100 group was decreased comparing with the LPS group. The concentration of cytokine of GR100 and GR400 group was decreased comparing with the LPS group. TH expression in the LC was increased in LPS group, but in GR100 and GR400 group was not shown significant decrease. Conclusion : According to this results obtained, GR has antidepressant effects by the anti inflammatory action through the suppression of HPA axis activity, not through the action against the catecholaminergic system.

Keywords

References

  1. Sapolsky RM1, Romero LM, Munck AU. How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions. Endocr Rev. 2000 ; 21(1) : 55-89.
  2. Millan MJ. Multi-target strategies for the improved treatment of depressive states:Conceptual foundations and neuronal substrates, drug discovery and therapeutic application. Pharmacol Ther. 2006 ; 110(2) : 135-370. https://doi.org/10.1016/j.pharmthera.2005.11.006
  3. Baldessarini RJ. The basis for amine hypotheses in affective disorder, A critical evaluation. Arch Gen Psychiatry. 1975 ; 32(9) : 1087-93. https://doi.org/10.1001/archpsyc.1975.01760270019001
  4. Sapolsky R, Rivier C, Yamamoto G, Plotsky P, Vale W. Interleukin-1 stimulates the secretion of hypothalamic corticotropin-releasing factor. Science. 1987 ; 238(4826) : 522-4. https://doi.org/10.1126/science.2821621
  5. Smith RS. The macrophage theory of depression. Med Hypotheses. 1991 ; 35(4) : 298-306. https://doi.org/10.1016/0306-9877(91)90272-Z
  6. Lee MS. Antidepressants and Related Drug Interactions. Koeran J Biol Psychiatry. 2000 ; 7(1) : 21-33.
  7. Ko YH, Kim SH. The Characteristics and Treatments of Major Depressive Disorder with Psychotic Features. Korean J. Pyschopharmacol. 2005 ; 16(5) : 341-50.
  8. Song HR, Woo YS, Bahk WM. Depression as an Inflammatory Disease. Korean J Psychopharmacol. 2013 ; 24(1) : 5-10.
  9. Woong DS, Shin Nong Bon Cho Gyung. Taiwan : Joong Hwa Seo Gwh. 1983 : 12-3.
  10. Ahn JH. Joong Yah Hak. Beijing : In Min Wi Seng. 1991 : 751-8.
  11. Kwon SO, Choi SM, Kim MH, Lee BB, Park MW, Lee YJ, Park HJ, Hahm DH. Antidepressant Effect of the Subchronic Administration of the Methanolic Extract of Wild-ginseng and Cultivated-ginseng in Mice Tail Suspension Test. J Korean Acupuncture Moxibustion Med Soc. 2009 ; 26(4) : 99-106.
  12. Hwang JM. Inhibitory effect of(E)-1-(3, 4-dihydroxystyryl)-3-(4-hydroxyphenetyl) urea compound on LPS-induced inflammatory responses in RAW 264.7 cells. Junbuk University. 2010.
  13. Lee JM. Effects of Jakyakkamchobuja-tang on Papain-induced Osteoarthritis in Mice. Daejeon University. 2012.
  14. Kim YJ. Effect of wild ginseng pharmacopuncture on immune system in an LPS-induced acute inflammatory rat model. SangJi University. 2010.
  15. Park HJ, Shim HS, Shim IS, Lee TH. Neural Mechanisms Underlying Antidepressant-Like Effects of Glycyrrhizae Radixs in Rats. Korean J Orient Physiol Pathol. 2010 ; 24(6) : 1053-8.
  16. Dantzer R, O'Connor JC, Lawson MA, Kelley KW. Inflammation-associated depression: From serotonin to kynurenine. Psychoneuroendocrinology. 2011 ; 36(3) : 426-36. https://doi.org/10.1016/j.psyneuen.2010.09.012
  17. Herman JP, Schafer MK-H, Young EA, Thompson R, Douglas J, Akil H, Watson SJ. Evidence for hippocampal regulation of neuroendocrine neurons of the hypothalamo-pituitary-adrenocortical axis. J Neurosci. 1989 ; 9(9) : 3072-82. https://doi.org/10.1523/JNEUROSCI.09-09-03072.1989
  18. Jin JI. Joong Guk Yak Hak Dae Jeon. Taiwan : Song Ak. 1990 : 256-9.
  19. Yagnik RM, Benzeroual KE. Tigecycline prevents LPS-induced release of pro-inflammatory and apoptotic mediators in neuronal cells. Toxicol In Vitro. 2013 ; 27(2) : 686-93 https://doi.org/10.1016/j.tiv.2012.11.015
  20. Dantzer R, O'Connor JC, Freund GG, Johnson RW, Kelley KW. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci. 2008 ; 9(1) : 46-56. https://doi.org/10.1038/nrn2297
  21. O'Connor JC, Lawson MA, Andre C, Moreau M, Lestage J, Castanon N, Kelley KW, Dantzer R. Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice. Mol Psychiatry. 2009 ; 14(5) : 511-22. https://doi.org/10.1038/sj.mp.4002148
  22. Hahn MK, Bannon MJ. Stress-induced c-fos expression in the rat locus coeruleus is dependent on neurokinin 1 receptor activation. Neuroscience. 1999 ; 94(4) : 1183-8. https://doi.org/10.1016/S0306-4522(99)00319-X
  23. Vazquez DM. Stress and the developing limbic-hypothalamic-pituitary-adrenal axis. Psychoneuroendocrinology. 1998 ; 23(7) : 663-700. https://doi.org/10.1016/S0306-4530(98)00029-8
  24. Kim YK. The role of cytokines in depression and their therapeutic implication. Korean J Pyschopharmacol. 2000 ; 11(4) : 304-12.
  25. Sakash JB, Byme GI, Lichtman A, Libby P. Cytokines induce indoleamine 2,3-dioxygenase expression in human atheroma-asociated cells: implications for persistent Chlamydophila pneumoniae infection. Infect Immun. 2002 ; 70(7) : 3959-61. https://doi.org/10.1128/IAI.70.7.3959-3961.2002
  26. Guillemin GJ, Kerr SJ, Pemberton LA, Smith DG, Smythe GA, Armati PJ, Brew BJ. IFN-beta1b induces kynurenine pathway metabolism in human macrophages: potential implications for multiple sclerosis treatment. J Interferon Cytokine Res. 2001 ; 21(12) : 1097-101. https://doi.org/10.1089/107999001317205231
  27. Neveu JP, Castanon N. Is there evidence for an effect of antidepressant drugs on the immune function? In: Dantzer R, Wollman EE, Yirmiya R, editors. Cytokines, stress, and depression. New York : Plenum. 1999 : 267-82.
  28. Xia Z, DePierre JW, Nassberger L. Tricyclic antidepressants inhibit IL-6, IL-$1\beta$ and TNF-$\alpha$ release in human blood monocytes and IL-2 and interferon-$\beta$ in T cells. Immunopharmacology. 1996 ; 34(1) : 27-37. https://doi.org/10.1016/0162-3109(96)00111-7
  29. Jacob MD, Harrison SC. Structure of an $I\kappa{B}$/NF-$\kappa{B}$ complex. Cell. 1998 ; 95(6) : 749-58. https://doi.org/10.1016/S0092-8674(00)81698-0
  30. Kim DS. A novel mechanism for constitutive NF-$\kappa{B}$ activation: I-$\kappa{B}$a depletion by transglutaminase 2 and mu-calpain occurs in parallel with the ubiquitin-proteasome pathway. Sungkyunwan University. 2011.
  31. Robert Ader. Psychoneuroimmunology. Burlington : Elsevier. 2007 : 50-4, 66-71, 281-318.
  32. Fujioka S, Niu J, Schmidt C, Sclabas GM, Peng B, Uwagawa T, Li Z, Evans DB, Abbruzzese JL, Chiao PJ. NF-$\kappa{B}$ and AP-1 Connection: Mechanism of NF-$\kappa{B}$-Dependent Regulation of AP-1 Activity. Mol Cell Biol. 2004 ; 24(17) : 7806-19. https://doi.org/10.1128/MCB.24.17.7806-7819.2004
  33. McDevitt RA, Szot P, Baratta MV, Bland ST, White SS, Maier SF, Neumaier JF. Stress-induced activity in the locus coeruleus is not sensitive to stressor controllability. Brain Res. 2009 ; 1285 : 109-18. https://doi.org/10.1016/j.brainres.2009.06.017