Human Intestinal Bacteria Mediate Reduction of the N-Oxides of Isoline and Monocrotaline to the Corresponding Parent Alkaloids

Jun Tang; Zhengtao Wang; Teruaki Akao; Masao Hattori

doi:10.14233/ajchem.2013.13283

Issue

Vol. 25 No. 4 (2013): Vol 25 Issue 4

Issue Published : November 1, 2012

This work is licensed under a Creative Commons Attribution 4.0 International License.

Human Intestinal Bacteria Mediate Reduction of the N-Oxides of Isoline and Monocrotaline to the Corresponding Parent Alkaloids

https://doi.org/10.14233/ajchem.2013.13283

Jun Tang

Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education and Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, P.R. China ; Department of Pharmacognosy, China Pharmaceutical University, Nanjing 210038, P.R. China

Zhengtao Wang

Department of Pharmacognosy, China Pharmaceutical University, Nanjing 210038, P.R. China ; Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, P.R. China

Teruaki Akao

Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-019, Japan

Masao Hattori

Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-019, Japan

Corresponding Author(s) : Jun Tang

tangj0205@gmail.com

Asian Journal of Chemistry, Vol. 25 No. 4 (2013): Vol 25 Issue 4
Article Published : November 1, 2012

Abstract

The role of human intestinal bacteria in the biotransformation of pyrrolizidine alkaloid N-oxides was investigated. Two naturally-occurring hepatotoxic pyrrolizidine alkaloids, isoline and monocrotaline and their N-oxides were incubated with a human fecal suspension in an in vitro model, respectively. The metabolites were isolated and purified by chromatographic techniques and identified by the spectral analyses and the metabolic profiles were further analyzed by a specific TLC method. Human intestinal bacteria showed high reduction effects on the pyrrolizidine alkaloid N-oxides but not on the resultant tertiary alkaloids, suggesting that IB may play a partial role in the cyclic conversion between each pyrrolizidine alkaloid and its N-oxide in vivo. This evidence implied the potential risk of the pyrrolizidine alkaloid-containing Chinese medicinal herbs to human health when used in decoctions.

Keywords

Isoline N-oxide Monocrotaline N-oxide Hepatotoxic pyrrolizidine alkaloids Human intestinal bacteria Chinese medicinal herbs

Tang, J., Wang, Z., Akao, T., & Hattori, M. (2012). Human Intestinal Bacteria Mediate Reduction of the N-Oxides of Isoline and Monocrotaline to the Corresponding Parent Alkaloids. Asian Journal of Chemistry, 25(4), 2027–2030. https://doi.org/10.14233/ajchem.2013.13283

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References

J. Tang and M. Hattori, Acta Pharm. Sin., 46, 762 (2011).
R.J. Huxtable, Pharmacol. Ther., 47, 371 (1990).
J. Tang, T. Akao, N. Nakamura, Z.T. Wang, K. Takagawa, M. Sasahara and M. Hattori, Drug Metab. Dispos., 35, 1832 (2007).
J. Tang, M. Zhang, Z.T. Wang, T. Akao, N. Nakamura and M. Hattori, J. Anal. Toxicol., 28, 11 (2004).
L. Jiang, M. Cheng, Q. Gao and J. Tang, China Pharm., 13, 1743 (2010).
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P.P. Fu, Q.S. Xia, G. Lin and M.W. Chou, Drug Metab. Rev., 36, 1 (2004).
Y.P. Wang, J. Yan, P.P. Fu and M.W. Chou, Toxicol. Lett., 155, 411 (2005).
G. Powis, M.M. Ames and J.S. Kovach, Cancer Res., 39, 3564 (1979).
P.S. Chu, M.W. Lame and H.J. Segall, Arch. Toxicol., 67, 39 (1993).
J. Tang, M. Zhang, Z.T. Wang, T. Akao, N. Nakamura, M. Hattori and G.J. Xu, Chin. J. Nat. Med., 1, 21 (2003).
J. Tang, M. Zhang, Z.T. Wang, T. Akao, N. Nakamura and M. Hattori, J. Chin. Pharm. Univ., 34, 499 (2003).
L.Q. Wang, M.R. Meselhy, Y. Li, G.W. Qin and M. Hattori, Chem. Pharm. Bull., 48, 1606 (2000).
L. Susag, M. Parvez, S. Mathenge and M.H. Benn, Phytochemistry, 54, 933 (2000).
C.G. Logie, M.R. Grue and J.R. Liddell, Phytochemistry, 37, 43 (1994).
S.R. Dueker, M.W. Lame, D. Morin, D.W. Wilson and H.J. Segall, Drug Metab. Dispos., 20, 275 (1992).
M.W. Chou, Y.P. Wang, J. Yan, Y.C. Yang, R.D. Beger, L.D. Williams, D.R. Doerge and P.P. Fu, Toxicol. Lett., 145, 239 (2003).

References

J. Tang and M. Hattori, Acta Pharm. Sin., 46, 762 (2011).

R.J. Huxtable, Pharmacol. Ther., 47, 371 (1990).

J. Tang, T. Akao, N. Nakamura, Z.T. Wang, K. Takagawa, M. Sasahara and M. Hattori, Drug Metab. Dispos., 35, 1832 (2007).

J. Tang, M. Zhang, Z.T. Wang, T. Akao, N. Nakamura and M. Hattori, J. Anal. Toxicol., 28, 11 (2004).

L. Jiang, M. Cheng, Q. Gao and J. Tang, China Pharm., 13, 1743 (2010).

E. Roeder, Pharmazie, 55, 711 (2000).

P.P. Fu, Q.S. Xia, G. Lin and M.W. Chou, Drug Metab. Rev., 36, 1 (2004).

Y.P. Wang, J. Yan, P.P. Fu and M.W. Chou, Toxicol. Lett., 155, 411 (2005).

G. Powis, M.M. Ames and J.S. Kovach, Cancer Res., 39, 3564 (1979).

P.S. Chu, M.W. Lame and H.J. Segall, Arch. Toxicol., 67, 39 (1993).

J. Tang, M. Zhang, Z.T. Wang, T. Akao, N. Nakamura, M. Hattori and G.J. Xu, Chin. J. Nat. Med., 1, 21 (2003).

J. Tang, M. Zhang, Z.T. Wang, T. Akao, N. Nakamura and M. Hattori, J. Chin. Pharm. Univ., 34, 499 (2003).

L.Q. Wang, M.R. Meselhy, Y. Li, G.W. Qin and M. Hattori, Chem. Pharm. Bull., 48, 1606 (2000).

L. Susag, M. Parvez, S. Mathenge and M.H. Benn, Phytochemistry, 54, 933 (2000).

C.G. Logie, M.R. Grue and J.R. Liddell, Phytochemistry, 37, 43 (1994).

S.R. Dueker, M.W. Lame, D. Morin, D.W. Wilson and H.J. Segall, Drug Metab. Dispos., 20, 275 (1992).

M.W. Chou, Y.P. Wang, J. Yan, Y.C. Yang, R.D. Beger, L.D. Williams, D.R. Doerge and P.P. Fu, Toxicol. Lett., 145, 239 (2003).

Issue

Vol. 25 No. 4 (2013): Vol 25 Issue 4

Human Intestinal Bacteria Mediate Reduction of the N-Oxides of Isoline and Monocrotaline to the Corresponding Parent Alkaloids

Corresponding Author(s) : Jun Tang

Abstract

Keywords

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