主 办:北 京 中 医 药 大 学
ISSN 1006-2157 CN 11-3574/R

JOURNAL OF BEIJIGN UNIVERSITY OF TRADITIONAL CHINE ›› 2016, Vol. 39 ›› Issue (8): 664-669.doi: 10.3969/j.issn.1006-2157.2016.08.011

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Screening succinate semialdehyde dehydrogenase inhibitors: an established model and its application in Tall Gastrodia Tuber*

LI Bi1, FANG Xiong1, CHU Fuhao1, XU Bing1, BI Siling2, ZHANG Chenze1, YAN Wenqiang1,
ZHANG Yuzhong2, WANG Penglong1#, LEI Haimin1#   

  1. 1 School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102;
    2 School of Preclinical Medicine, Beijing University of Chinese Medicine
  • Received:2016-02-17 Online:2016-08-31 Published:2016-08-31

Abstract: Objective To establish a model of screening succinate semialdehyde dehydrogenase (SSADH) inhibitors with anti-epilepsy effects, then using this model to find out the effective components in Tall Gastrodia Tuber (Latin: Rhizoma Gastrodiae, pinyin:Tianma) and some analogues and to study their structure-activity relationship. Methods First, SSADH enzyme system fluid was prepared, and the correlation of activity and optical density of SSADH was evaluated using UV spectrophotometry. Then, after the screening method of SSADH activity was established by optimization of reaction temperature, reaction time, concentration of NAD+, SSA and SSADH, and pH of buffer on the SSADH activity, p-hydroxybenzaldehyde (HBA), a positive drug recorded in literature, was applied to verify the model. And the structural analogues of HBA were measured and the mechanism was analyzed. Results The screening model was established successfully, proved by HBA test. The UV detective system and its buffers of SSADH activity were determined with reaction temperature at 37 ℃ for 30 min,and detect wave at 340 nm. The structure-activity of HBA on GABA-T was as the same as that of vanillic aldehyde, and —OH and —CHO of benzene ring were the essential groups for inhibition SSADH. Conclusion The model established in this paper can be used for high throughput screening SSADH inhibitors and may guide the study of analogues of SSADH inhibitors and their mechanism.

Key words: inhibitor of succinate semialdehyde dehydrogenase, structure-activity relationship, anti-epilepsy, Rhizoma Gastrodiae, 4-hydroxybenzaldehyde, high throughput screening

CLC Number: 

  • R284.2