Planta Med 2001; 67(9): 877-880
DOI: 10.1055/s-2001-18844
Letter

© Georg Thieme Verlag Stuttgart · New York

In vitro Effects of Hydroxybenzaldehydes from Gastrodia elata and their Analogues on GABAergic Neurotransmission, and a Structure-Activity Correlation

Jeoung-Hee Ha1 , Son-Moon Shin2 , Soo-Kwan Lee3 , Jin-Sook Kim4 , Uk-Seob Shin4 , Keun Huh4 , Jung-Ae Kim4 , Chul-Soon Yong4 , Nam-Jae Lee5 , Dong-Ung Lee5
  • 1 Department of Pharmacology, College of Medicine, Yeungnam University, Taegu, Korea
  • 2 Department of Pediatrics, Sungkyunkwan University, School of Medicine, Samsung Cheil Hospital, Korea
  • 3 Department of Pediatrics, College of Medicine, Yeungnam University, Taegu, Korea
  • 4 College of Pharmacy, Yeungnam University, Gyongsan, Korea
  • 5 Department of Biochemistry, College of Natural Science, Dongguk University, Kyongju, Korea
Further Information

Publication History

December 19, 2000

March 4, 2001

Publication Date:
06 December 2001 (online)

Abstract

The present study was designed to characterize the modulatory effects of the constituents of Gastrodia elata and their analogues on the GABAergic neurotransmission. 4-Hydroxybenzaldehyde (1) and 4-hydroxy-3-methoxybenzaldehyde (4) inhibited potently the activity of GABA transaminase (IC50 = 4.1 and 5.4 μg/ml, respectively), while the activity of another constituent, 4-hydroxybenzyl alcohol (2), was very weak. Further investigation with 10 analogues revealed a structure-activity correlation, suggesting that the aldehyde group and the hydroxy group at C-4 are necessary for the inhibitory effect on the enzyme activity. Some potent enzyme inhibitors were examined for the effect on the radioligands to the GABAA receptor complexes of rat cerebral cortices. Among them, the component 4 dose-dependently increased (20 - 30 %) the binding of [3 H]flunitrazepam in the presence of GABA.

References

  • 1 Tang W, Eisenbrand G. Chinese drugs of plant origin. Chemistry, pharmacology, and use in traditional and modern medicine. Berlin · Heidelberg; Springer Verlag 1992: 545-7
  • 2 Taguchi H, Yosioka I, Yamasaki K, Kim I H. Studies on the constituents of Gastrodia elata Blume.  Chemical & Pharmaceutical Bulletin. 1981;  29 55-62
  • 3 Zhou J, Yang Y B, Pu X Y. The phenolic compounds of fresh Gastrodia elata Blume.  Yunnan Chih Wu Yen Chiu. 1980;  2 370-4
  • 4 Yun-Choi H S, Pyo M K, Park K M. Isolation of 3-O-(4′-hydroxybenzyl)-β-sitosterol and 4-[4′-(4″-hydroxybenzyloxy)benzyloxy]benzyl methyl ether from fresh tubers of Gastrodia elata .  Archives of Pharmacal Research (published by the Pharmaceutical Society of Korea). 1998;  21 357-60
  • 5 Huh K, Yi S J, Shin U K, Park J M. Effect of the ether fraction of Gastrodia elata methanol extract on the pentylenetetrazole-induced seizures.  Journal of Applied Pharmacology (published by the Korean Pharmaceutical Sciences). 1995;  3 199-204
  • 6 Park Y K, Kang B S, Yun E K, Kang S I, Park C H, Lee D U, Ha J H, Huh K. Effects of some sedative oriental medicines on neurotransmission and antioxidative system in vitro .  Yakhak Hoeji (published by the Pharmaceutical Society of Korea). 2000;  44 22-8
  • 7 Ha J H, Lee D U, Lee J T, Kim J S, Yong C S, Kim J A, Ha J S, Huh K. 4-Hydroxybenzaldehyde from Gastrodia elata Blume is active in the GABAergic neuromodulation.  Journal of Ethnopharmacology. 2000;  73 329-33
  • 8 Ha J H, Lee D U, Kang B S. Agonistic activities to the benzodiazepine receptor by extracts of medicinal plants (I). Screening of some sedative plant extracts.  Saengyakhak Hoeji (published by Korean Society of Pharmacognosy). 1999;  30 211-5
  • 9 Ha J H, Lee D U, Yong C S, Kim J A, Huh K. Agonistic activities to the benzodiazepine receptor by extracts of medicinal plants (II). Activities of component and active fractions from Gastrodia elata .  Saengyakhak Hoeji (published by Korean Society of Pharmacognosy). 1999;  30 284-9
  • 10 Basile A S, Jones E A, Skolnick P. The pathogenesis and treatment of hepatic encephalopathy: evidence for the involvement of benzodiazepine receptor ligands.  Pharmacological Reviews. 1991;  43 28-71
  • 11 Drugan R C, Basile A S, Ha J H, Ferland R J. The protective effects of stress control may be mediated by increased brain levels of benzodiazepine receptor agonists.  Brain Research. 1994;  661 127-36
  • 12 Ha J H, Pannell L, Drugan R C, Ferland R, Basile A S. Neuroscience Protocols. Elsevier Sciences 1996: 1-12
  • 13 Lee D U, Kang S I, Yoon S H, Budesinsky M, Kasal A, Mayer K K, Wiegrebe W. A new steroidal alkaloid from the roots of Cynanchum caudatum .  Planta Medica. 2000;  66 480-2
  • 14 Bergmeyer H U. Method of enzymatic analysis. Vol 2, New York; Academic Press 1983: 191-2

Prof. Dr. Dong-Ung Lee

Department of Biochemistry

College of Natural Science

Dongguk University

Kyongju 780-714

Korea

Email: dulee@mail.dongguk.ac.kr

Fax: +82-54-742-9833