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[Discover potential inhibitors of 5-LOX and LTA4H from Rhei Radix et Rhizoma, Notopterygii Rhizoma et Radix and Genitana Macrophyllae Radix based on molecular simulation methods].
Zhongguo Zhong Yao Za Zhi. 2017 Dec; 42(23):4494-4502.ZZ

Abstract

5-lipoxygenase (5-LOX) and leukotriene A4 hydrolase (LTA4H), as the major targets of 5-LOX branch in the arachidonic acid (AA) metabolic pathway, play an important role in the treatment of inflammation. Rhei Radix et Rhizoma, Notopterygii Rhizoma et Radix and Genitana Macrophyllae Radix have clear anti-inflammation activities. In this paper, the targets of 5-LOX and LTA4H were used as the research carrier, and Hiphop module in DS4.0 (Discovery studio) was used to construct ingredients database for preliminary screening of three traditional Chinese medicines based on target inhibitor pharmacophore, so as to obtain 5-LOX and LTA4H potential active ingredients. The ingredients obtained in initial pharmacophore screening were further screened by using CDOCKER module, and the screening rules were established based on the score of initial compound and the key amino acids to obtain 12 potential 5-LOX inhibitors and 7 potential LTA4H inhibitors. To be more specific, the potential 5-LOX inhibitors included 6 ingredients in Rhei Radix et Rhizoma, such as procyanidins B2-3,3'-O-double gallate and revandchinone 2; four ingredients in notopterygium, such as dodecanoic acid and so on. On the other hand, potential LTA4H inhibitors included revandchinone 1, revandchinone 4 in Rhei Radix et Rhizoma, tridecanoic acid, tetracosanoic acid and methyl eicosanoate in Notopterygii Rhizoma et Radix, montanic acid methyl ester and N-docosanoyl-O-aminobenzoate in Genitana Macrophyllae Radix and so on. The molecular simulation methods were highly efficient and time-saving to obtain the potential inhibitors of 5-LOX and LTA4H, which could provide assistance for discovering the chemical quality indicators of anti-inflammatory efficacy of three Chinese herbs, and may be helpful to promote the whole-process quality control of three Chinese herbs.

Authors+Show Affiliations

Key Laboratory of Traditional Chinese Medicine Foundation and New Drug Research, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China.Key Laboratory of Traditional Chinese Medicine Foundation and New Drug Research, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China.Key Laboratory of Traditional Chinese Medicine Foundation and New Drug Research, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China.Key Laboratory of Traditional Chinese Medicine Foundation and New Drug Research, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China.Key Laboratory of Traditional Chinese Medicine Foundation and New Drug Research, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China.

Pub Type(s)

Journal Article

Language

chi

PubMed ID

29376243

Citation

Gu, Yu, et al. "[Discover Potential Inhibitors of 5-LOX and LTA4H From Rhei Radix Et Rhizoma, Notopterygii Rhizoma Et Radix and Genitana Macrophyllae Radix Based On Molecular Simulation Methods]." Zhongguo Zhong Yao Za Zhi = Zhongguo Zhongyao Zazhi = China Journal of Chinese Materia Medica, vol. 42, no. 23, 2017, pp. 4494-4502.
Gu Y, Zhang X, Chen YK, et al. [Discover potential inhibitors of 5-LOX and LTA4H from Rhei Radix et Rhizoma, Notopterygii Rhizoma et Radix and Genitana Macrophyllae Radix based on molecular simulation methods]. Zhongguo Zhong Yao Za Zhi. 2017;42(23):4494-4502.
Gu, Y., Zhang, X., Chen, Y. K., Zhao, B. W., & Zhang, Y. L. (2017). [Discover potential inhibitors of 5-LOX and LTA4H from Rhei Radix et Rhizoma, Notopterygii Rhizoma et Radix and Genitana Macrophyllae Radix based on molecular simulation methods]. Zhongguo Zhong Yao Za Zhi = Zhongguo Zhongyao Zazhi = China Journal of Chinese Materia Medica, 42(23), 4494-4502. https://doi.org/10.19540/j.cnki.cjcmm.2017.0201
Gu Y, et al. [Discover Potential Inhibitors of 5-LOX and LTA4H From Rhei Radix Et Rhizoma, Notopterygii Rhizoma Et Radix and Genitana Macrophyllae Radix Based On Molecular Simulation Methods]. Zhongguo Zhong Yao Za Zhi. 2017;42(23):4494-4502. PubMed PMID: 29376243.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [Discover potential inhibitors of 5-LOX and LTA4H from Rhei Radix et Rhizoma, Notopterygii Rhizoma et Radix and Genitana Macrophyllae Radix based on molecular simulation methods]. AU - Gu,Yu, AU - Zhang,Xu, AU - Chen,Yan-Kun, AU - Zhao,Bo-Wen, AU - Zhang,Yan-Ling, PY - 2017/11/05/received PY - 2018/1/30/entrez PY - 2018/1/30/pubmed PY - 2019/5/9/medline KW - 5-lipoxygenase KW - anti-inflammatory KW - leukotriene A4 hydrolase KW - molecular docking KW - pharmacophore KW - traditional Chinese medicine KW - virtual screening SP - 4494 EP - 4502 JF - Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica JO - Zhongguo Zhong Yao Za Zhi VL - 42 IS - 23 N2 - 5-lipoxygenase (5-LOX) and leukotriene A4 hydrolase (LTA4H), as the major targets of 5-LOX branch in the arachidonic acid (AA) metabolic pathway, play an important role in the treatment of inflammation. Rhei Radix et Rhizoma, Notopterygii Rhizoma et Radix and Genitana Macrophyllae Radix have clear anti-inflammation activities. In this paper, the targets of 5-LOX and LTA4H were used as the research carrier, and Hiphop module in DS4.0 (Discovery studio) was used to construct ingredients database for preliminary screening of three traditional Chinese medicines based on target inhibitor pharmacophore, so as to obtain 5-LOX and LTA4H potential active ingredients. The ingredients obtained in initial pharmacophore screening were further screened by using CDOCKER module, and the screening rules were established based on the score of initial compound and the key amino acids to obtain 12 potential 5-LOX inhibitors and 7 potential LTA4H inhibitors. To be more specific, the potential 5-LOX inhibitors included 6 ingredients in Rhei Radix et Rhizoma, such as procyanidins B2-3,3'-O-double gallate and revandchinone 2; four ingredients in notopterygium, such as dodecanoic acid and so on. On the other hand, potential LTA4H inhibitors included revandchinone 1, revandchinone 4 in Rhei Radix et Rhizoma, tridecanoic acid, tetracosanoic acid and methyl eicosanoate in Notopterygii Rhizoma et Radix, montanic acid methyl ester and N-docosanoyl-O-aminobenzoate in Genitana Macrophyllae Radix and so on. The molecular simulation methods were highly efficient and time-saving to obtain the potential inhibitors of 5-LOX and LTA4H, which could provide assistance for discovering the chemical quality indicators of anti-inflammatory efficacy of three Chinese herbs, and may be helpful to promote the whole-process quality control of three Chinese herbs. SN - 1001-5302 UR - https://www.unboundmedicine.com/medline/citation/29376243/[Discover_potential_inhibitors_of_5_LOX_and_LTA4H_from_Rhei_Radix_et_Rhizoma_Notopterygii_Rhizoma_et_Radix_and_Genitana_Macrophyllae_Radix_based_on_molecular_simulation_methods]_ DB - PRIME DP - Unbound Medicine ER -