Hindawi Publishing Corporation 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 Dong-Ming Tsai, 1,2 Jaw-Jou Kang, 3 Shoei-Sheng Lee, 4 San-Yuan Wang, 2,5 I-Lin Tsai, 2,4 Guan-Yuan Chen, 2,4 Hsiao-Wei Liao, 4 Li Wei-Chu, 6 Ching-Hua Kuo, 2,4 and Y. Jane Tseng 1,2,4,5 1 Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 106, Taiwan 2 he Metabolomics Core Laboratory, Center of Genomic Medicine, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 106, Taiwan 3 Institute of Toxicology, College of Medicine, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 106, Taiwan 4 Department of Pharmacy, College of Medicine, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 106, Taiwan 5 Department of Computer Science and Information Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 106, Taiwan 6 Sheng Chang Pharmaceutical Co., Ltd., Jung-Li, Taiwan Correspondence should be addressed to Y. Jane Tseng; yjtseng@csie.ntu.edu.tw Received 8 January 2013; Revised 26 February 2013; Accepted 27 February 2013 Academic Editor: Mark Moss Copyright © 2013 Dong-Ming Tsai et al. his 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. 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. his 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 5mg/kgbw/day or 7.5 mg/kg bw/day for 10 days. Madouling and BFAJT were given at an equivalence of AA 0.5mg/kg bw/day for 21 days. Nephrotoxicity was evaluated by metabolomics and histopathology. he urinary metabolomics proiles were characterized by 1 H NMR spectroscopy. he spectral data was analyzed with partial least squares discriminant analysis, and the signiicant diferential metabolites between groups were identiied. he result showed diferent 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. he compositions of the compound remedy did not diminish the nephrotoxicity caused by AA. 1. Introduction Aristolochic acids (AAs) are potent nephrotoxic agents [1, 2] that are found primarily in the plant genera Aristolochia and Asarum [3, 4]. hese herbs have been used as a component of herbal remedies in traditional Chinese medicine (TCM). Herbal remedies containing Aristolochia and Asarum have been used to relieve symptoms such as cough, arthritic pain, and gastrointestinal problems [5, 6]. However, chronic kidney injury may occur in humans ater a prolonged intake of these Aristolochiaceous herbs. Inadvertent replacement of Stephania tetrandra by Arsitolochia fangchi has caused rapidly progressive interstitial renal ibrosis (also named Chinese herbs nephropathy) in young women on a slimming regimen