注册 English

Studies on the intestinal absorption of the alkaloids in the Gancaofuzi decoction in a Caco-2 cell culture system by UPLC–MS/MS analysis

Ru Ding ,  Yong Jian ,  Hong Kan ,  Zhong-Ying Liu ,  Shu Liu ,  Zhi-Qiang Liu ,  Jun Zhou

downloadPDF
引用本文: Ru Ding,  Yong Jian,  Hong Kan,  Zhong-Ying Liu,  Shu Liu,  Zhi-Qiang Liu,  Jun Zhou. Studies on the intestinal absorption of the alkaloids in the Gancaofuzi decoction in a Caco-2 cell culture system by UPLC–MS/MS analysis[J]. Chinese Chemical Letters, 2016, 27(6): 915-919. doi: 10.1016/j.cclet.2016.03.001 shu
Citation:  Ru Ding,  Yong Jian,  Hong Kan,  Zhong-Ying Liu,  Shu Liu,  Zhi-Qiang Liu,  Jun Zhou. Studies on the intestinal absorption of the alkaloids in the Gancaofuzi decoction in a Caco-2 cell culture system by UPLC–MS/MS analysis[J]. Chinese Chemical Letters, 2016, 27(6): 915-919. doi: 10.1016/j.cclet.2016.03.001 shu

Studies on the intestinal absorption of the alkaloids in the Gancaofuzi decoction in a Caco-2 cell culture system by UPLC–MS/MS analysis

  • a School of Pharmacy, Jilin University, Changchun 130021, China;

  • b National Centre of Mass Spectrometry in Changchun & Jilin Province Key Laboratory of Chinese Medicine Chemistry and Mass Spectrometry, Changchun Institute of Applied Chemistry, Chinese Academy of Science, Changchun 130022, China;

  • c Guizhou Province and Chinese Academy of Sciences, Key Laboratory of Chemistry for Natural Products, Guiyang 550002, China;

  • d College of Chinese Medicine Material, Jilin Agricultural University, Changchun 130118, China;

  • e Department of Orthopedics, The Fourth People's Hospital of Guiyang, Guiyang 550000, China

  • 基金项目:

    This research was supported by the National Natural Science Foundation of China (No. 81173507) and the Science Foundation of Jilin province (No. 20150414040GH).

摘要: In this study, the Caco-2 cell monolayer model was used to research the characteristic absorption and efflux of five diterpenoid alkaloids in Gancaofuzi decoction. An ultra performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) method was developed for the determination of the simulated intestinal transport of five diterpenoid alkaloids with reserpine as internal standard. The use of the apparent permeability coefficient (Papp) and efflux rate (Er) was instituted to evaluate the intestinal absorption of the alkaloids. Transport of the five alkaloids in Caco-2 cell monolayer model was observed to better understand whether the intestinal absorption of alkaloids was influenced by the compatibility of four herbs in Gancaofuzi decoction. The results show that the Papp values of the five diterpenoid alkaloids were all more than 1×10-6 cm/s, confirming that the processes of permeability were valid. The flux of the alkaloids was time-dependent, and the intestinal absorption mechanism of the five alkaloids was mainly based on passive transport. The compatibility of Heishunpian, Baizhu, Guizhi and Gancao can reduce the intestinal absorption of alkaloids, especially the most toxic hypaconitine, and the attenuated effect of mixed herbal water extracts was better than that of different herbs' water extracts combination. The results prove that compatibility of four herbs in Gancaofuzi decoction is rational.

English

    1. [1] J.F. Li, Y.L. Wu, Clinical application of licorice aconite decoction, J. Yunnan Univ. Tradit. Chin. Med. 34 (2011) 47.

    2. [2] Q.T. Gao, Study on the Therapeutic Basis of Traditional Chinese Medicinal Preparation Gancaofuzi Decoction, Shenyang Pharmaceutical University, Shenyang, 2005.

    3. [3] Y.P. Kao, M.J. Liu, Q.Z. Yuan, Chemical constituents and pharmacological activities of aconite, Shaanxi J. Tradit. Chin. Med. 31 (2010) 1658-1660.

    4. [4] M. Hazawa, K. Wada, K. Takahashi, et al., Suppressive effects of novel derivatives prepared from Aconitum alkaloids on tumor growth, Investig. New Drugs 27 (2009) 111-119.

    5. [5] S.Z. Chen, Effect of Wu Tou Decoction on Rheumatoid Arthritis and its Possible Mechanism, Guangzhou University of Traditional Chinese Medicine, Guangzhou, 2006.

    6. [6] P.J. Wang, X.G. Shi, Z. Ge, X.D. Peng, Z.S. Huang, Effects of aconite decoction on peripheral blood T lymphocytes of adjuvant arthritis rat, Pharmacol. Clin. Chin. Mater. Med. 23 (2007) 9-10.

    7. [7] W.D. Xu, X. Wang, C. Wang, et al., Study on Rougui and Fuzi's role in tonifying kidney yang by Shenqiwan from hypothalamic-pituitary-adrenal axis, J. Zhejiang Chin. Med. Univ. 38 (2014) 831-836.

    8. [8] X.Y. Hu, G.P. Peng, R.Y. Chen, Antagonism of liquorice toward arrhythmia induced by prepared aconite root, J. Nanjing Univ. Tradit. Chin. Med. 12 (1996) 64.

    9. [9] H. Chen, Outlines of pharmacological action of glycyrrhizae, Strait Pharm. J. 17 (2005) 37-41.

    10. [10] X.J. Yao, Analyses of the Chemical Composition of Traditional Chinese Medicinal Preparation Gancaofuzi decoction, Jilin University, Changchun, 2013.

    11. [11] P. Stenberg, C.A.S. Bergström, K. Luthman, P. Artursson, Theoretical predictions of drug absorption in drug discovery and development, Clin. Pharmacokinet. 41 (2002) 877-899.

    12. [12] Z.L. Lu, Y. Feng, D.S. Xu, X. Lin, Y. Yang, Application of Caco-2 cell model in peroral absorption of Chinese materia medica and its mechanism, Chin. Tradit. Herb. Drugs 37 (2006) 616-619.

    13. [13] M. Markowska, R. Oberle, S. Juzwin, et al., Optimizing Caco-2 cell monolayers to increase throughput in drug intestinal absorption analysis, J. Pharmacol. Toxicol. Methods 46 (2001) 51-55.

    14. [14] P. Augustijns, R. Mols, HPLC with programmed wavelength fluorescence detection for the simultaneous determination of marker compounds of integrity and P-gp functionality in the Caco-2 intestinal absorption model, J. Pharm. Biomed. Anal. 34 (2004) 971-978.

    15. [15] A.R. Hilgers, R.A. Conradi, P.S. Burton, Caco-2 cell monolayers as a model for drug transport across the intestinal mucosa, Pharm. Res. 7 (1990) 902-910.

    16. [16] B. Waltenberger, B. Avula, M. Ganzera, et al., Transport of sennosides and sennidines from Cassia angustifolia and Cassia senna across Caco-2 monolayersan in vitro model for intestinal absorption, Phytomedicine 15 (2008) 373-377.

    17. [17] N. Li, In Vitro Study on Absorption and Mechanism of Diester-type Alkaloids in Aconite Extract, Jilin University, Changchun, 2009.

    18. [18] J. Zhao, A.H. Liang, Caco-2 cell model and its application in the absorption and transportation research of Chinese materia medica, Chin. J. Exp. Tradit. Med. Form. 15 (2009) 79-83.

    19. [19] X. Li, In Vitro Studies on Absorptive Transportion of Alkaloids in Radix Aconiti Kusnezoffii After Processing and Combination, Jilin University, Changchun, 2012.

    20. [20] J.W. Ma, In Vitro Study on Mechanism of Attenuation in Aconitum by Processing and Compatibility, Jilin University, Changchun, 2014.

    21. [21] Z. Wang, Y. Kurosaki, T. Nakayama, T. Kimura, Mechanism of gastrointestinal absorption of glycyrrhizin in rats, Biol. Pharm. Bull. 17 (1994) 1399-1403.

    22. [22] T.J. Han, F.R. Song, Z.Y. Liu, et al., Studies of the intestinal transport of the diterpenoid alkaloids in the Aconitum carmichaeli combined with different medicinal herbs in a Caco-2 cell culture system with UPLC/MS, Acta Chim. Sin. 69 (2011) 1795-1802.

    23. [23] M. Yang, X.B. Liu, Q.D. Huang, The increasing effect and reducing ill effect principle of compatibility of radix Aconiti Lateralis preparata and radix Glycyrrhizae, Lishizhen Med. Mater. Med. Res. 14 (2003) 197-198.

    24. [24] C.X. Chen, S.J. Xu, Research progress on the material basis and function of the compatibility between Licorice, Ginger and Aconite, Tradit. Chin. Drug Res. Clin. Pharmacol. 17 (2006) 472-476.

  • 加载中
WeChat 扫一扫看文章
计量
  • PDF下载量:  0
  • 文章访问数:  1453
  • HTML全文浏览量:  17
文章相关
  • 收稿日期:  2015-12-15
  • 修回日期:  2016-01-29
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索

/

返回文章

All Rights Reserved by the Chinese Chemical Society   中国化学会 版权所有 京ICP备05002797号

本系统由北京仁和汇智信息技术有限公司开发    技术支持: info@rhhz.net