YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

In silico Prediction and In vitro Screening of Biological Activities and Pharmacokinetics for the Major Compounds in Chong Myung Tang

가상 검색 및 시험관 시험을 이용한 총명탕 중 주성분들에 대한 약물작용 및 대사 예측

  • Published : 2007.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Chong Myung Tang is consisted of three medicinal herbs (Acori Graminei Rhizoma, Polygalae Radix and Hoelen cum Radix). It has been used as a medicine for the purpose of learning and memory improvement. In this paper, Chong Myung Tang was screened the biological activities for Alzheimer's disease. The extract (70% ethanol) of Acari Graminei Rhizoma (1 mg/ml) showed that acetylcholinesterase (AChE) and amyloid beta ($A{\beta}$) peptide aggregation inhibitory potency are 43.1% and 76.5%, respectively. The extract of Polygalae Radix showed inhibitory activity against $A{\beta}_{1-42}$ peptide aggregation (51.5%). To predict the drug-likeness, oral absorption ability; blood-brain barrier (BBB) penetraion rate, mutagenecity and carcinogenicity; in silico screening was performed against 16 compounds in the three medicinal herbs. According to the results, all compounds have appropriate chemical structures as medicines. The six compounds in Acori Graminei Rhizoma and the five compounds in Hoelen cum Radix showed excellent oral absorption rate and BBB penetration rate. The four compounds in Polygalae Radix showed excellent oral absorption rate, but their BBB penetration was presented low rate. And, the extract of Hoelen cum Radix didn't show AChE and $A{\beta}_{1-42}$ peptide aggregation inhibitory activities in vitro. Therefore, their activity in brain may be other mechanism. According to all of the results, in silico prediction technology is convenient and effective to determine biological active compounds in medicinal herbs.

Keywords

References

  1. 計浚 : 東醫寶鍵, 서울, 南山堂 (1987)
  2. 陳羅電等 : 古今圖書集成醫部全錄(第7冊), 北京, 人民衛生出版社, 2150 (1983)
  3. 彭杯仁 : 中華名醫方濟大全, 北京, 金盾出版社, 748 (1990)
  4. 김영욱 外 : 聰明湯이 健忘誘導白鼠의 學習과 記憶에 미치는 影響. 韓方再活醫學科學會誌 8, 464 (1998)
  5. 박지운, 정인철, 이상룡 : 聰明湯과 木槿皮聰明湯이 CT105와 ${\beta}A$로 유도된 Alzheimer's disease 病態 모델에 미치는 영향. 동의신경정신과학회지 17, 37 (2006)
  6. 하수영, 정인철, 이상룡 : 聰明湯과 山査聰明湯이 Alzheimer's disease 病態 모델에 미치는 影響. 동의신경정신과학회지 17,59 (2006)
  7. 오영진, 김보경 : 聰明湯과 香附子聰明湯의 추출물, 나노분말 제형을 이용한 치매에 관한 연구. 동의신경정신과학회지 17,79 (2006)
  8. Lipinski, C. A., Lombardo, E, Dominy, B. W. and Feeney, E J. : Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 23, 3 (1997)
  9. Clark, D. E. and Pickett, S. D.: Computational methods for the prediction of drug-likeness. DDT 5, 49 (2000)
  10. Hann, M. M., Leach, A. R. and Harper, G. : Molecular complexity and its impact on the probability of finding leads for drug discovery. J. Chem. Inform. Comp. Sci. 41, 856 (2001) https://doi.org/10.1021/ci0000474
  11. Li, A. E : Screening for human ADME/Tox drug properties in drug discovery. DDT 6, 357 (2001)
  12. Curatolo, W. : Physical chemical properties of oral drug candidates in the discovery and exploratory development settings. PSTT 1, 387 (1998)
  13. Navia, M. A. and Chaturvedi, E R.: Design principles for orally bioavailable drugs. DDT 1, 179 (1996)
  14. Yamashita, S., Furubayashi, X, Kataoka, M., Sakane, T., Sezaki, H. and Tokuda, H. : Optimized conditions for prediction of intestinal drug permeability using Caco-2 cells. Eur. J. Pharm. Sci. 10, 195 (2000)
  15. Krishna, G., Chen, K., Lin, C. and Nomeir, A. A.: Permeability of lipophilic compounds in drug discovery using in-vitro human absorption model, Caco-2. Int. J. Pharm. 222, 77 (2001)
  16. Irvine, J. D., Takahashi, L. and Lockhart, K.: MDCK (Madin-Darby canine kidney) cells: A tool for membrane permeability screening. J. Pharm. Sci. 88, 28 (1999)
  17. Eddy, E. E, Maleef, B. E., Hart, T. K. and Smith, P. L.: In vitro models to predict blood-brain barrier permeability. Adv. Drug Deliv. Rev. 23, 185 (1997)
  18. Pardridge, W. M. : Transport of small molecules through the blood-brain barrier: biology and methodology. Adv. Drug Deliv. Rev. 15, 5 (1995)
  19. Agatonovic-Kustrin, S. and Beresford, R. : Basic concepts of artificial neural network (ANN) modeling and its application in pharmaceutical research. J. Pharm. Biomed. Anal. 22, 717 (2000)
  20. Basheer, I. A. and Hajmeer, M. : Artificial neural networks: fundamentals, computing, design and application. J. Microbiol. Methods 43, 3 (2000)
  21. 생약학교재편찬위원회: 생약학, 동명사 (2006)
  22. PreADMET (ver. 1.0) is a web-based application for predicting ADMET data, http://preadmet.bmdrc.org, Bioinformatics & Molecular Design Research Center, Seoul, Republic of Korea
  23. Mukherjee, R K., Kumar, V, Mai, M. and Houghton, E J. : In vitro acetylcholinesterase inhibitory activity of the essential oil from Acorus calamus and its main constituents. Planta Med. 73, 283 (2007) https://doi.org/10.1055/s-2007-967114
  24. Irie, Y. and Keung, W. M. : Rhizoma acori graminei and its active principles protect PC-12 cells from the toxic effect of amyloid-p peptide. Brain Research 963, 282 (2003) https://doi.org/10.1016/S0006-8993(02)04050-7
  25. Kanokmedhakul, S., Kanokmedhakul, K. and Lekphrom, R. : Bioactive Constituents of the Roots of Polyalthia cerasoides. J. Nat. Prod. in press (2007)
  26. Chaieb, K., Zmantar, X, Ksouri, R., Hajlaoui, H., Mahdouani, K., Abdelly, C. and Bakhrouf, A.: Antioxidant properties of the essential oil of Eugenia caryophyllata and its antifungal activity against a large number of clinical Candida species. Mycoses. 50, 403 (2007) https://doi.org/10.1111/j.1439-0507.2007.01391.x
  27. Fernandes, E. S., Passos, G. E, Medeiros, R., da Cunha, E M., Ferreira, J., Campos, M. M., Pianowski, L. E and Calixto, J. B.: Anti-inflammatory effects of compounds alpha-humulene and (-)-trans-caryophyllene isolated from the essential oil of Cordia verbenacea. Eur. J. Pharmacol. 569, 228 (2007) https://doi.org/10.1016/j.ejphar.2007.04.059
  28. Karakida, E, Ikeya, Y, Tsunakawa, M., Yamaguchi, X, Ikarashi, Y, Takeda, S. and Aburada, M. : Cerebral protective and cognition-improving effects of sinapic acid in rodents. Biol. Pharm Bull. 30, 514 (2007) https://doi.org/10.1248/bpb.30.514