Induction of Growth Hormone Release by the Extracts of Lonicera japonica $T_{HUNB.}$

인동 추출물의 성장호르몬 유발 효과

  • Jung, Dae-Young (Department of Herbal Medicine, Korea Institute of Oriental Medicine) ;
  • Lee, Ho-Young (Department of Herbal Medicine, Korea Institute of Oriental Medicine) ;
  • Ha, Hye-Kyung (Department of Herbal Medicine, Korea Institute of Oriental Medicine) ;
  • Jung, Da-Young (Department of Herbal Medicine, Korea Institute of Oriental Medicine) ;
  • Kang, Sam-Sik (Natural Products Research Institute, Seoul National University) ;
  • Kim, Chung-Sook (Department of Herbal Medicine, Korea Institute of Oriental Medicine)
  • 정대영 (한국한의학연구원 한약제제연구부) ;
  • 이호영 (한국한의학연구원 한약제제연구부) ;
  • 하혜경 (한국한의학연구원 한약제제연구부) ;
  • 정다영 (한국한의학연구원 한약제제연구부) ;
  • 강삼식 (서울대학교 천연물과학연구소) ;
  • 김정숙 (한국한의학연구원 한약제제연구부)
  • Published : 2003.09.30

Abstract

Lonicerae Flos (LF) has been used as an anticancer, anti-viral, and anti-inflammatory agent in traditional herbal medicine. In this study, induction of rat growth hormone (rGH) by addition of methanol (MeOH) extract of LF of Lonicerae (L.) Folium or several constituents of L. Folium were carried out in the pituitary cell culture system. Induced rGH level by addition of 70% MeOH extract of LF was increased to $732.65{\pm}105.64%$ of control (n=18, p<0.01), however, the other sequential fractions were not significantly different from the control. Ochnaflavone, a constituent of L. Folium, induced rGH level in the cell culture to $329.73{\pm}160.00%$ of control (n=6, p<0.01). An I..v. injection of the MeOH extract of LF did not increase plasma rGH level in anesthetized rats. Unfortunately, the MeOH extract of LF induced prolactin and LH release about 7 and 5 fold of the control, respectively (p<0.05, each). In conclusions, 70% MeOH extract of LF exerted induction of rGH release in rat pituitary cell culture. Further studies to investigate mechanisms of the inducded rGH by LF are in progress.

Keywords

References

  1. Lee, Y. S. (2002) The Korean Herbal Pharmacopoeia, 304. Korea Food and Drug Administration, Seoul
  2. Lee, S. J., Shin, E. J., Son, K. H., Chang, H. W., Kang, S. S., and Kim, H. P. (1995) Anti-inflammatory activity of the major constituents of Lonicera japonica. Arch. Pharma. Res. 18(2): 133-135 https://doi.org/10.1007/BF02979147
  3. Lee, J. H., Ko, W. S., Kim, Y. H., Kang, H. S., Kim, H. D., and Choi, B. T. (2001) Anti-inflammatory effect of the aqueous extract from Lonicera japonica flower is related to inhibition of NF-$\kappa$B activation through reducing I-$\kappa$B$\alpha$ degradation in rat liver. Int. J. Mol. Med. 7(1): 79-83
  4. Han, D. S., Baek, K. H., Kim, Y. O., Choi, K W., Kwag, J. S., and Baek, S. H. (1998) Development of Anticancer Agents from Korean Medicinal Plants. Part 6. Cytotoxic Activity of the Ethyl Acetate Soluble Fraction of Lonicerae flos against Human Oral Epitheloid Carcinoma Cells. Kor. J. Pharmacogn. 29(1): 22-27
  5. Argente, J., Pozo, J., and Chowen, J. A. (1996) The growth hormone axis: control and effects. Horm. Res. 45 (Suppl 1): 9-11 https://doi.org/10.1159/000184818
  6. Bowers,C. Y., Momany, F., Reynolds, G. A., Chang, D., Hong, A., and Chang, K. (1980) Structure activity relationships of a synthetic pentapeptide that specifically releases growth hormone in vitro. Endocrinology 106(3): 663-667 https://doi.org/10.1210/endo-106-3-663
  7. Gertz, B. J., Barret, J. S., Eisenhandler, R., Krupa, D. A., Wittreich, J. M., Seibold, J. R., and Schneider, S. H. (1993) GH response in man to L-692,429, a novel nonpetide mimic of GHRP-6. J. Clin. Endocrinol. Metab. 77(5): 1393-1397 https://doi.org/10.1210/jc.77.5.1393
  8. Gertz, B. J., Sciberras, D. G., Yogendran, L., Christie, K., Bador, K., Krupa, D., Wittreich, J. M., and James I. (1994) L-692,429, a nonpeptide growth hormone (GH) secretagogue, reverses glucocorticoid suppression of GH secretion. J. Clin. Endocrinol. Metab. 79(3): 745-749 https://doi.org/10.1210/jc.79.3.745
  9. Patchett, A .A., Nargund, R. P., Tata, J. R., Chen, M.-H., Barakat, K. J., Johnston, D. B. R., Cheng, K., Chan, W.. W.S., Buder, B., Hickey, G., Jacks, T., Schleim, K., Pong, S.-S., Chaung, L.-Y. P., Chen, H. Y., Frazier, E., Leung, K. H., Chiu, S.-H. L., and Smith, R. G. (1995) Design and biological activities of L-163,191 (MK-0677) : A potent and orally active growth hormone secretagogue. Proc. Natl. Acad. Sci. USA. 92: 7001-7005 https://doi.org/10.1073/pnas.92.15.7001
  10. Kojima, M., Hosoda, H., Date, Y., Nakazato, M., Matsuo, H., and Kangawa, K.(1999) Ghrelin is a growth hormone releasing acylated peptide from stomach. Nature 402(6762): 656-660 https://doi.org/10.1038/45230
  11. Nagamine, J., Nagata, R., Seki, H., Nomura-Akimaru, N., Deki, Y., Kumagai, K., Taiji, M., and Noguchi, H. (2001) Pharmacological profile of a new orally active growth hormone secretagogue, SM-130686. J. Endocrinol. 171(3): 481-489 https://doi.org/10.1677/joe.0.1710481
  12. Son, K. H., Park, J. O., Chung, K. C., Chang, H. W., Kim, H. P., Kim, J. S., and Kang, S. S. (1992) Flavonoids from the aerial parts of Lonocera laponica. Arch. Pharm. Res. 15(4): 365-370 https://doi.org/10.1007/BF02974114
  13. Son, K. H., Kim, J. S., Kang, S. S., Kim H. P., and Chang, H. W. (1994) Isolation of flavonoids from Lonicera japonica. Kor. J. Pharmacogn. 25(1): 24-27
  14. Son, K. H., Jung, K. Y., Chang, H. W., Kim, H. P., and Kang, S. S. (1994) Triterpenoid saponines from the aerial parts of Lonicera japonica. hytochemistry 35(4): 1005-1008 https://doi.org/10.1016/S0031-9422(00)90656-3
  15. Kim, C., Ha, H., Kim, J. S., Kim, Y. T., Kwon, S. C., and Park, S. W. (2003) Induction of growth hormone by the roots of Astragalus membranaceus in pitnitary cell culture. Arch. Pharm. Res. 26(1): 34-39 https://doi.org/10.1007/BF03179928
  16. Carlsson, L. M., Clark, R. G., and Robinson, I. C. (1990) Sex difference in growth hormone feedback in the rat. J. Endocrinol. 126(1): 27-35 https://doi.org/10.1677/joe.0.1260027
  17. Stirling, R. G. and Shin, S. H. (1990) A high concentration of dopamine preferentially permitted release of newly synthesized prolactin. Mol. Cell Endoerinol. 70(1): 65-72 https://doi.org/10.1016/0303-7207(90)90059-H
  18. Taya, K. and Sasamoto, S. (1990) Involvement of the adrenal gland in the suckling-induced decrease in LH and FSH secretion and the concomitant increase in prolactin secretion in the rat. J. Endocrinol. 125(2): 279-285 https://doi.org/10.1677/joe.0.1250279
  19. Bartlett, J. M., Weinbauer, G. F., and Nieschlag, E. (1989) Differential effects of FSH and testosterone on the maintenance of spermatogenesis in the adult hypophysectomized rat. J. Endocrinol. 121(1): 49-58 https://doi.org/10.1677/joe.0.1210049
  20. Donda, A., Reymond, F., Rey, F., and Lemarchand-Beraud, T. (1990) Sex steroids modulate the pituitary parameters involved in the regulation of TSH secretion in the rat. Acta Endocrinol (Copenh). 122(5): 577-584
  21. Plotsky, P. M. and Vale, W. (1985) Patterns of growth hormone-releasing factor and somatostatin secretion into the hypophysial-portal circulation of rat. Science 230: 461-463 https://doi.org/10.1126/science.2864742
  22. Wehrenberg, W. B., Brazeau, P., Luben, R., Bohlen, P., and Guillemin, R. (1982) Inhibition of the pulsatile secretion of growth hormone by monoclonal antibodies to the hypothalamic growth hormone releasing factor (GRF). Endocrinology 111(6): 2147-2148 https://doi.org/10.1210/endo-111-6-2147
  23. Howard, A. D., Feighner, S. D., Cully, D. F., Arena, J. P., Liberator, P. A., Rosenblum, C. I., Hamelin, M., Hreniuk, D. L., Palyha, O. C., Anderson, J., Paress, P. S., Diaz, C., Chou, M., Liu, K. K., McKee, K. K., Pong, S. S., Chaung, L.Y, Elbrecht, A., Dashkevicz, M., Heavens, R., Rigby, M., Sirinathsinghji, D. J., Dean, D.C., Melillo, D. G., Patchett, A. A., Nargund, R., Griffin, P. R., DeMartino, J. A., Gupta, S. K., Schaeffer, J. M., Smith, R. G., and Van der Ploeg, L. H. (1996) A receptor in pituitary and hypothalamus that functions in growth hormone release. Science 273: 974-977卡湦潲搬⁐⹁⸀蠗?⨀砈?⨀堕?⨀粸?⨀฀考憺Ȁ憺Ȁ̀￿￿￿￿ၖ?⨀ĀĀ฀쌸舃憺Ȁ憺Ȁ̀￿￿Ā粸?⨀ᑀ⹷က₪舀Ⴝ﾿缀舀퀔?⨀￿￿￿㼂฀⓽✀奈돀邰?⨀塨?⨀怣?⨀턌돐耣?⨀?잖⨀蠣?⨀ꤌ덐頣?⨀ꠌ蠌Ā̀਀ȀԀ਀ऀ਀ఀĀ樀敮最
  24. Guan, X. M., Yu, H., Palyha, O. C., McKee, K. K., Feighner, S. D., Sirinathsinghji, D. J., Smith, R. G., Van der Ploeg, L. H., and Howard, A. D. (1997) Distribution of mRNA encoding the growth hormone secretagogue receptor in brain and peripheral tissues. Brain Res. Mol. Brain Res. 48: 23-29 https://doi.org/10.1016/S0169-328X(97)00071-5
  25. Schaeffer, H. J. and Sirotkin, A. V. (1995) The release of insulin-like growth factor-I by luteinized human granulosa cells in vitro: regulation by growth hormone, oxytocin, steroids and cAMP-dependent intracellular mechanisms. Exp. Clin. Endocrinol. Diabetes. 103(6): 361-366. https://doi.org/10.1055/s-0029-1211379
  26. Greenspan, F. S. and Gardner, D. G. (2001) Basic & Clinical Endocrinology, 6th Edition, 114. McGraw-Hill Co. Whitby, ON, Canada
  27. Robbins, R. J., Leidy, J. W. Jr., and Landon, R. M. (1985) The effects of growth hormone, prolactin, corticotropin, and thyrotropin on the production and secretion of somatostatin by hypothalamic cells in vitro. Endocrinology 117(2): 538-543 https://doi.org/10.1210/endo-117-2-538