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Evidence-Based Complementary and Alternative Medicine
Volume 2013, Article ID 263757, 10 pages
http://dx.doi.org/10.1155/2013/263757
Research Article

Metabolomic Analysis of Complex Chinese Remedies: Examples of Induced Nephrotoxicity in the Mouse from a Series of Remedies Containing Aristolochic Acid

1Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 106, Taiwan
2The Metabolomics Core Laboratory, Center of Genomic Medicine, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 106, Taiwan
3Institute of Toxicology, College of Medicine, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 106, Taiwan
4Department of Pharmacy, College of Medicine, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 106, Taiwan
5Department of Computer Science and Information Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 106, Taiwan
6Sheng Chang Pharmaceutical Co., Ltd., Jung-Li, Taiwan

Received 8 January 2013; Revised 26 February 2013; Accepted 27 February 2013

Academic Editor: Mark Moss

Copyright © 2013 Dong-Ming Tsai et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Aristolochic acid nephropathy is caused by aristolochic acid (AA) and AA-containing herbs. In traditional Chinese medicine, a principle called “Jun-Chen-Zou-Shi” may be utilized to construct a remedial herbal formula that attempts to mitigate the toxicity of the main ingredient. This study used Bu-Fei-A-Jiao-Tang (BFAJT) to test if the compound remedy based on a principle of “Jun-Chen-Zou-Shi” can decrease the toxicity of AA-containing herbs. We compared the three toxicities of AA standard, Madouling (an Aristolochia herb), and a herbal formula BFAJT. AA standard was given for BALB/c mice at a dose of 5 mg/kg bw/day or 7.5 mg/kg bw/day for 10 days. Madouling and BFAJT were given at an equivalence of AA 0.5 mg/kg bw/day for 21 days. Nephrotoxicity was evaluated by metabolomics and histopathology. The urinary metabolomics profiles were characterized by 1H NMR spectroscopy. The spectral data was analyzed with partial least squares discriminant analysis, and the significant differential metabolites between groups were identified. The result showed different degrees of acute renal tubular injuries, and metabolomics analysis found that the kidney injuries were focused in proximal renal tubules. Both metabolomics and pathological studies revealed that AA standard, Madouling, and BFAJT were all nephrotoxicants. The compositions of the compound remedy did not diminish the nephrotoxicity caused by AA.