Wei Jia

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Organization: Shanghai Jiao Tong University

Department: School of Pharmacy

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Chemicals
References

Plasma Metabolite Profiles of Alzheimer’s Disease and Mild Cognitive Impairment

Co-reporter:Gang Wang;Yi Zhou;Feng-Jie Huang;Hui-Dong Tang;Xu-Hua Xu;Jia-Jian Liu;Ying Wang;Yu-Lei Deng;Ru-Jing Ren;Wei Xu;Jian-Fang Ma;Yi-Nan Zhang;Ai-Hua Zhao;Sheng-Di Chen

Journal of Proteome Research May 2, 2014 Volume 13(Issue 5) pp:2649-2658

Publication Date(Web):2017-2-22

DOI:10.1021/pr5000895

Previous studies have demonstrated altered metabolites in samples of Alzheimer’s disease (AD) patients. However, the sample size from many of them is relatively small and the metabolites are relatively limited. Here we applied a comprehensive platform using ultraperformance liquid chromatography-time-of-flight mass spectrometry and gas chromatography-time-of-flight mass spectrometry to analyze plasma samples from AD patients, amnestic mild cognitive impairment (aMCI) patients, and normal controls. A biomarker panel consisting of six plasma metabolites (arachidonic acid, N,N-dimethylglycine, thymine, glutamine, glutamic acid, and cytidine) was identified to discriminate AD patients from normal control. Another panel of five plasma metabolites (thymine, arachidonic acid, 2-aminoadipic acid, N,N-dimethylglycine, and 5,8-tetradecadienoic acid) was able to differentiate aMCI patients from control subjects. Both biomarker panels had good agreements with clinical diagnosis. The 2 panels of metabolite markers were all involved in fatty acid metabolism, one-carbon metabolism, amino acid metabolism, and nucleic acid metabolism. Additionally, no altered metabolites were found among the patients at different stages, as well as among those on anticholinesterase medication and those without anticholinesterase medication. These findings provide a comprehensive global plasma metabolite profiling and may contribute to making early diagnosis as well as understanding the pathogenic mechanism of AD and aMCI.Keywords: Alzheimer’s disease; amnestic mild cognitive impairment; biomarkers; metabolomics; plasma;

Metabonomics Approach to Assessing the Metabolism Variation and Endoexogenous Metabolic Interaction of Ginsenosides in Cold Stress Rats

Co-reporter:Zhihao Zhang; Xiaoyan Wang; Jingcheng Wang; Zhiying Jia; Yumin Liu; Xie Xie; Chongchong Wang

Journal of Proteome Research 2016 Volume 15(Issue 6) pp:1842-1852

Publication Date(Web):May 6, 2016

DOI:10.1021/acs.jproteome.6b00015

Metabolic profiling technology, a massive information provider, has promoted the understanding of the metabolism of multicomponent medicines and its interactions with endogenous metabolites, which was previously a challenge in clarification. In this study, an untargeted GC/MS-based approach was employed to investigate the urinary metabolite profile in rats with oral administration of ginsenosides and the control group. Significant changes of urinary metabolites contents were observed in the total ginsenosides group, revealing the impact of ginsenosides as indicated by the up- or down-regulation of several pathways involving neurotransmitter-related metabolites, tricarboxylic acid (TCA) cycle, fatty acids β-oxidation, and intestinal microflora metabolites. Meanwhile, a targeted UPLC-QQQ/MS-based metabonomic approach was developed to investigate the changes of urinary ginsenoside metabolites during the process of acute cold stress. Metabolic analysis indicated that upstream ginsenosides (rg1, re, and rf) increased significantly, whereas downstream ginsenosides (ck, ppd, and ppt) decreased correspondingly after cold exposure. Finally, the relationships between ginsenosides and significantly changed metabolites were investigated by correlation analysis.

A rapid ultra-performance liquid chromatographyelectrospray Ionisation mass spectrometric method for the analysis of saponins in the adventitious roots of Panax notoginseng

Co-reporter:Mo Dan;Guoxiang Xie;Xianfu Gao;Xiangbao Long;Mingming Su;Aihua Zhao;Tie Zhao;Mingmei Zhou;Yunping Qiu

Phytochemical Analysis 2009 Volume 20( Issue 1) pp:68-76

Publication Date(Web):

DOI:10.1002/pca.1099

Abstract

Introduction

Saponins are bioactive compounds employed in the prevention and treatment of cardiovascular and cerebrovascular diseases. The adventitious roots of Panax notoginseng may offer an alternative source of saponins. Identification and determination of saponins in the crude extract is challenging owing to their similar structures and the lack of standards.

Objective

To develop a rapid, sensitive and accurate method based on solid-phase extraction followed by ultra-performance liquid chromatography–electrospray ionisation mass spectrometry (UPLC-ESI-MS) for the identification and quantification of saponins in P. notoginseng.

Methodology

Following extraction using Waters Oasis^TM HLB cartridges, the analytes were subjected to a UPLC system with a Waters Acquity BEH C₁₈ chromatographic column and a binary mobile phase system consisting of 0.05% formic acid in water and acetonitrile under gradient elution conditions, with final detection by ESI-MS in the positive ion mode.

Results

The UPLC-ESI-MS method gave limits of detection and quantification within the range 0.015–0.382 and 0.052–1.124 µg/mL, respectively, for 15 studied saponins. The instrumentation/injection precision (RSD) was 4.5% for a low concentration and 3.2% for an intermediate concentration sample. The intra- and inter-day repeatability was less than 2.65% (RSD). The method described was validated using spiked samples with different amounts of saponin standards.

Conclusion

This UPLC-ESI-MS assay provides a suitable quality control method for the tentative identification and determination of major biological active constituents in adventitious and native roots of P. notoginseng. Copyright © 2008 John Wiley & Sons, Ltd.

Gut microbiota: a potential new territory for drug targeting

Co-reporter:Wei Jia, Houkai Li, Liping Zhao & Jeremy K. Nicholson

Nature Reviews Drug Discovery 2008 7(2) pp:123

Publication Date(Web):2008-02-01

DOI:10.1038/nrd2505

The emerging influence of intestinal microorganisms on human health has led to the prospect of modulating gut microbiota composition as a novel therapeutic strategy. In this article, Jia and colleagues discuss the rationale behind this approach, identify conditions to which this may be applied, and suggest technologies and strategies for the development of gut microbiota-targeted therapies.

Metabonomic and Metallomic Profiling in the Amniotic Fluid of Malnourished Pregnant Rats

Co-reporter:Qing Shen, Xin Li, Yunping Qiu, Mingming Su, Yumin Liu, Houkai Li, Xiaoyan Wang, Xiangyu Zou, Chonghuai Yan, Lan Yu, Sheng Li, Chunling Wan, Lin He and Wei Jia

Journal of Proteome Research 2008 Volume 7(Issue 5) pp:2151-2157

Publication Date(Web):2017-2-22

DOI:10.1021/pr700776c

Epidemiology and studies in animal models have revealed that prenatal malnutrition is highly correlated with abnormal fetal neurodevelopment. We present here a combined metabonomic and metallomic profiling technique to associate the metabolic and trace-elemental composition variations of rat amniotic fluid (AF) in malnourished pregnant rats with the retardation of fetal rat neurodevelopment. The AF samples from three groups of pregnant Sprague–Dawley rats, which were fed either a normal diet, a low-protein diet, or “a famine diet”, were subjected to GC/MS and ICP/MS combined with multivariate data analysis (MVDA). PCA scores plot of both GC/MS and ICP/MS data showed similar and unique metabolic signatures of AF in response to the different diets. Rats in the famine group released increased amounts of glycine, inositol, putrescine, and rubidium and decreased amounts of methionine, dopa, tryptophan, glutamine, zinc, cobalt, and selenium in the AF. These discriminable variations in the AF may indicate the abnormality of a number of metabolic pathways in fetal rats including the folate cycle and methionine pathway, the monoamine pathway, and tri-iodothyronine (T3) metabolism. The abnormalities may be the result of metabolites or elemental differences or a combination of both. This study demonstrates the potential of combining profiling of small-molecule metabolites and trace elements to broaden the understanding of biological variations associated with fetal neurodevelopment induced by environmental perturbation.

Mass Spectrometry-Based Metabolic Profiling of Rat Urine Associated with General Toxicity Induced by the Multiglycoside of Tripterygium wilfordii Hook. f.

Co-reporter:Minjun Chen, Yan Ni, Hongquan Duan, Yunping Qiu, Congying Guo, Yang Jiao, Huijuan Shi, Mingming Su and Wei Jia

Chemical Research in Toxicology 2008 Volume 21(Issue 2) pp:288

Publication Date(Web):January 19, 2008

DOI:10.1021/tx7002905

We propose here a combined gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS) metabolic profiling strategy to elucidate the toxicity in rats induced by orally administered multiglycosides of Tripterygium wilfordii Hook. f. (GTW) in multiple organs including the kidney, liver, and testis. Overnight 12-h urine samples were collected from Sprague–Dawley male rats exposed to GTW (100 mg/kg/day, n = 6) and healthy controls (n = 6) at predose and at the 1st, 3rd, 6th, 10th, and 14th day postdose for both GC/MS and LC/MS analyses. The integrated urinary MS data were analyzed via multivariate statistical techniques such as principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) to identify the differential metabolites and pertinent altered biological pathways in response to the herbal toxin. The liver, kidney, and testis were also assessed using conventional histopathological examinations at the end point of the experiment. This work indicates that GTW caused a time-dependent toxic effect at a high dose as revealed by the perturbed metabolic regulatory network involving disorders in energy metabolism, elevated amino acid and choline metabolism pathways, as well as altered structure of gut flora. This integrated MS-based metabolic profiling approach has been able to capture and probe the metabolic alterations associated with the onset and progression of multiorgan toxicity induced by GTW, thereby permitting a comprehensive understanding of systemic toxicity for phytochemicals and other types of xenobiotic agents.

Multiparametric analysis of amino acids and organic acids in rat brain tissues using GC/MS

Co-reporter:Jingchao Lin;Mingming Su;Xiaoyan Wang;Yunping Qiu;Houkai Li;Jin Hao;Hongzhou Yang;Mingmei Zhou;Chao Yan

Journal of Separation Science 2008 Volume 31( Issue 15) pp:2831-2838

Publication Date(Web):

DOI:10.1002/jssc.200800232

Abstract

Using design of experiment (DOE) theory coupled with multivariate statistical analysis, we have developed a simple and reliable GC/MS-based analytical assay for simultaneous analysis of amino acids and organic acids in rat brain tissue samples. The process of water extraction (pH 10.0) was extensively evaluated using brain tissue samples and a set of 21 reference standards. Acceptable calibration curves were obtained over a wide concentration range, 0.2–35.0 μg/mL for standards and 15.0–2.4 mL/g (tissue) for brain tissue samples. The precision was mostly better than 10% for both the mixed standards and the brain tissue samples. The brain tissue samples exhibited good stability within 48 h with RSD generally less than 15%. Furthermore, the developed analytical method was successfully applied in distinguishing the subtle variation among different parts of the brain tissues, such as cerebral cortex, hippocampus, and thalamus.

Ultra-performance LC/TOF MS analysis of medicinal Panax herbs for metabolomic research

Co-reporter:Guoxiang Xie;Robert Plumb;Mingming Su;Zhaohui Xu;Aihua Zhao;Mingfeng Qiu;Xiangbao Long;Zhong Liu

Journal of Separation Science 2008 Volume 31( Issue 6-7) pp:1015-1026

Publication Date(Web):

DOI:10.1002/jssc.200700650

Abstract

In this study, metabolite profiling of five medicinal Panax herbs including Panax ginseng (Chinese ginseng), Panax notoginseng (Sanchi), Panax japonicus (Rhizoma Panacis Majoris), Panax quinquefolium L. (American ginseng), and P. ginseng (Korean ginseng) were performed using ultra-performance LC-quadrupole TOF MS (UPLC-QTOFMS) and multivariate statistical analysis technique. Principal component analysis (PCA) of the analytical data showed that the five Panax herbs could be separated into five different groups of phytochemicals. The chemical markers such as ginsenoside Rf, 20(S)-pseudoginsenoside F11, malonyl gisenoside Rb1, and gisenoside Rb2 accountable for such variations were identified through the loadings plot of PCA, and were identified tentatively by the accurate mass of TOFMS and partially verified by the available reference standards. Results from this study indicate that the proposed method is reliable for the rapid analysis of a group of metabolites present in herbal medicines and other natural products and applicable in the differentiation of complex samples that share similar chemical ingredients.

Metabolite profiling of Panax notoginseng using UPLC–ESI-MS

Co-reporter:Mo Dan, Mingming Su, Xianfu Gao, Tie Zhao, Aihua Zhao, Guoxiang Xie, Yunping Qiu, Mingmei Zhou, Zhong Liu, Wei Jia

Phytochemistry 2008 Volume 69(Issue 11) pp:2237-2244

Publication Date(Web):August 2008

DOI:10.1016/j.phytochem.2008.04.015

The metabolite profiling of different parts of Panax notoginseng was carried out using rapid ultra-performance liquid chromatography–electrospray ionization mass spectrometry (UPLC–ESI-MS) and multivariate statistical analysis. Principal component analysis (PCA) of the UPLC–ESI-MS data showed a clear separation of compositions among the flower buds, roots and rhizomes of P. notoginseng. The saponins accounting for such variations were identified through the corresponding loadings weights and were further verified by accurate mass, tandem mass and retention times of available standard saponins using UPLC quadrupole time-of-flight mass spectrometer (UPLC–QtofMS). Finally, the influential factors of different metabolic phenotypes of P. notoginseng was elucidated. The currently proposed UPLC–ESI-MS/MS analytical method coupled with multivariate statistical analysis can be further utilized to evaluate chemical components obtained from different parts of the plant and/or the plant of different geographical locations, thereby classifying the medicinal plant resources and potentially elucidating the mechanism of inherent phytochemical diversity.UPLC–ESI-MS/MS coupled with multivariate statistical analysis was used for metabolic profiling and identification of multiple saponins in Panax notoginseng revealing saponin differences and critical markers among different parts of P. notoginseng.

Application of ultra-performance LC-TOF MS metabolite profiling techniques to the analysis of medicinal Panax herbs

Co-reporter:Guo X. Xie;Yan Ni;Ming M. Su;Yuan Y. Zhang;Ai H. Zhao;Xian F. Gao

Metabolomics 2008 Volume 4( Issue 3) pp:248-260

Publication Date(Web):2008 September

DOI:10.1007/s11306-008-0115-5

The morphological appearance and some ingredients of Panax ginseng, Panax notoginseng and Panaxjaponicus of the Panax genus are similar. However, their pharmacological activities are obviously different due to the significant differences in the types and quantity of saponins in each herb. In the present study, ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOFMS) was used to profile the abundances of metabolites in the three medicinal Panax herbs. Multivariate statistical analysis technique, that is, principle component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were used to discriminate between the Panax samples. PCA of the analytical data showed a clear separation of compositions among the three medicinal herbs. The critical markers such as chikusetsusaponin IVa, ginsenoside R0, ginsenoside Rc, ginsenoside Rb1, ginsenoside Rb2 and ginsenoside Rg2 accountable for such variations were identified through the corresponding loading weights, and the tentative identification of biomarkers is completed by the accurate mass of TOFMS and high resolution and high retention time reproducibility performed by UPLC. The proposed analytical method coupled with multivariate statistical analysis is reliable to analyze a group of metabolites present in the herbal extracts and other natural products. This method can be further utilized to evaluate chemical components obtained from different plants and/or the plants of different geographical locations, thereby classifying the medicinal plant resources and potentially elucidating the mechanism of inherent phytochemical diversity.

Metabolic profiling reveals therapeutic effects of Herba Cistanches in an animal model of hydrocortisone-induced 'kidney-deficiency syndrome'

Co-reporter:Yunping Qiu;Minjun Chen;Mingming Su;Guoxiang Xie;Xin Li

Chinese Medicine 2008 Volume 3( Issue 1) pp:

Publication Date(Web):2008 December

DOI:10.1186/1749-8546-3-3

Herba Cistanches (Roucongrong) is effective in treating Shenxu Zheng ('kidney-deficiency syndrome'). However, the mechanisms and systemic metabolic responses to the herbal intervention are unclear.Using GC-MS-based metabolic profiling, we investigated the metabolic responses to Herba Cistanches intervention in a rat model of the hydrocortisone-induced 'kidney-deficiency syndrome'.The metabolic profiles of the rats after hydrocortisone injection deviated from the pre-dose metabolic state at different time points, ranging from day 1 to day 10, whereas the metabolic profiles of the rats treated with both hydrocortisone and water extract of Herba Cistanches returned to the pre-dose state on day 10.The intervention of Herba Cistanches caused a systemic recovery from the hydrocortisone-induced metabolic perturbation in rats. This study also demonstrates that metabolic profiling is useful in studying therapeutic mechanisms of herbal medicines.

Application of ethyl chloroformate derivatization for gas chromatography–mass spectrometry based metabonomic profiling

Co-reporter:Y. Qiu, M. Su, Y. Liu, M. Chen, J. Gu, J. Zhang, W. Jia

Analytica Chimica Acta 2007 Volume 583(Issue 2) pp:277-283

Publication Date(Web):5 February 2007

DOI:10.1016/j.aca.2006.10.025

A new combined gas chromatography and mass spectrometry (GC–MS) method has been developed suitable for the urine sample treatment in aqueous phase with ethyl chloroformate (ECF) derivatization agents. The method has been extensively optimized and validated over a broad range of different compounds and urine samples. Analysis of test metabolite derivatives, containing spiked standards, or rat urine exhibited acceptable linearity, satisfactory intra-batch precision (repeatability) and stability, relative standard deviations (R.S.D.) less than 10 and 15% within 48 h, respectively. The quantification limits were 150–300 pg on column for most metabolites. Recovery of several representative compounds, at different concentrations, ranged from 70 to 120%, with R.S.D. better than 10% for rat urine. We were able to generally eliminate potentially confounding variables such as medium complexity, different urea concentrations, and/or derivatization procedure variability. Metabonomic profiling of 1,2-dimethylhydrazine (DMH)-induced precancerous colon rat urine using GC–MS with ECF derivatization was performed to evaluate the proposed method. The analytical variation of the method was smaller than the biological variation in the rat urine samples, proving the suitability of the method to analyze differences in the metabonome of a living system with perturbed metabolic network. Thus, the proposed GC–MS analytical method is reliable to analyze a large variety of metabolites and can be used to investigate human pathology including disease onset, progression, and mortality.

Simultaneous determination of 17 ginsenosides in rat urine by ultra performance liquid chromatography–mass spectrometry with solid-phase extraction

Co-reporter:Xiaoyan Wang, Tie Zhao, Xianfu Gao, Mo Dan, Mingmei Zhou, Wei Jia

Analytica Chimica Acta 2007 Volume 594(Issue 2) pp:265-273

Publication Date(Web):2 July 2007

DOI:10.1016/j.aca.2007.05.032

A rapid analytical method for quantifying 17 ginsenosides in rat urine by ultra performance liquid chromatography (UPLC) coupled to electrospray ionization mass spectrometry (ESI-MS) is described. All analytes were extracted by solid-phase extraction optimized to obtain good recovery and quantified using digoxin as an internal standard. ESI-MS was optimized for different cone voltages at positive ionization mode to allow simultaneous analysis of all analytes in a relatively short time. Qualitative methodological considerations, including the linear range, precision, limit of quantification, limit of detection, recovery and sensitivity are also provided.

Determination of Endogenous Metabolites in Obesity Rat Urine by Pressurized Capillary Electrochromatography with Ethyl Chloroformate Derivatization

Co-reporter:Guo-Xiang Xie, Ming-Feng Qiu, Ai-Hua Zhao, Li Peng, Gu Xue, Jia Wei

Chinese Journal of Analytical Chemistry 2007 Volume 35(Issue 8) pp:1111-1115

Publication Date(Web):August 2007

DOI:10.1016/S1872-2040(07)60073-5

Pressurized capillary electrochromatography (pCEC) method was developed to analyze metabolites in normal and obesity rat urine with ethyl chloroformate derivatization. The separation was performed on a capillary column (EP-150-30/50-5-C18), and good resolution was obtained with the mobile phase of water (0.01% TFA)−95% acetonitrile (0.01% TFA) using the following gradient: 0–30 min, 0–50 % B; 30–40 min, 50%–75% B. Under the optimized conditions, such as pressure of 13000 kPa, applied voltage of 2 kV, flow rate of 0.08 ml min−1, and room temperature, the contents of metabolites in the urine of normal and obesity rats were obtained. Under the optimum conditions, the correction coefficients were 0.9988–0.9999 in the range of 1.25–500 g l−1. The intra- and inter-day precisions were less than 5%. The average recoveries ranged from 95.9% to 103.2%. The method is simple, sensitive, and accurate for the determination of endogenous metabolites in rat urine sample.

Immunosuppressive ent-Kaurene Diterpenoids from Isodon serra

Co-reporter:Ai-Hua Zhao;Yan Zhang;Zhao-Hui Xu;Jian-Wen Liu

Helvetica Chimica Acta 2004 Volume 87(Issue 12) pp:3160-3166

Publication Date(Web):21 DEC 2004

DOI:10.1002/hlca.200490281

Three new enmein-type ent-kaurenoids, i.e., the two pairs 1 and 2 of 20-epimers and the (20R)-isomer 3, besides the seven known diterpenoids 4–10, were isolated from the aerial parts of Isodon serra. Their structures were elucidated by spectroscopic techniques and X-ray diffraction. The immunosuppressive effect for T-lymphocytes proliferation induced by Con A in BALB/c mouse was evaluated for the isolates 1–10. They all displayed a remarkable inhibitory effect, with multi-glycosides of Tripterygium wilfordii as positive reference substance (Table 3).

Metabolic profiling reveals disorder of amino acid metabolism in four brain regions from a rat model of chronic unpredictable mild stress

Co-reporter:Yan Ni, Mingming Su, Jinchao Lin, Xiaoyan Wang, ... Wei Jia

FEBS Letters (23 July 2008) Volume 582(Issue 17) pp:2627-2636

Publication Date(Web):23 July 2008

DOI:10.1016/j.febslet.2008.06.040

Chronic stress is closely linked to clinical depression, which could be assessed by a chronic unpredictable mild stress (CUMS) animal model. We present here a GC/MS-based metabolic profiling approach to investigate neurochemical changes in the cerebral cortex, hippocampus, thalamus, and remaining brain tissues. Multi-criteria assessment for multivariate statistics could identify differential metabolites between the CUMS-model rats versus the healthy controls. This study demonstrates that the significantly perturbed metabolites mainly involving amino acids play an indispensable role in regulating neural activity in the brain. Therefore, results obtained from such metabolic profiling strategy potentially provide a unique perspective on molecular mechanisms of chronic stress.

In vitro and in vivo evaluation of the anti-asthmatic activities of fractions from Pheretima

Co-reporter:Xiangping Chu, Zhaohui Xu, Dazheng Wu, Aihua Zhao, Mingmei Zhou, Mingfeng Qiu, Wei Jia

Journal of Ethnopharmacology (22 May 2007) Volume 111(Issue 3) pp:490-495

Publication Date(Web):22 May 2007

DOI:10.1016/j.jep.2006.12.013

Pheretima (family Megascolecidae) has been documented as a potent agent for the treatment of cough and breathing difficulty in traditional Chinese medicine for nearly 2000 years. The water extract of Pheretima was separated into three fractions of the ethanolic precipitate, the alkaline fraction and the acidic fraction. Among the three fractions, the acidic fraction showed the most potent spasmolytic effects on histamine-induced contractions in isolated guinea pig tracheal rings, and the most inhibitory activities on increase of short circuit current induced by carbachol in isolated rat tracheal epitheliums with the IC50 values of 0.15 and 0.08 mg/ml, respectively. Further in vivo studies also displayed that the acidic fraction could protect experimental asthma model induced by the combination of histamine and acetylcholine chloride in guinea pigs to prolong the latent periods of asthma (P < 0.05) and significantly decrease the cough frequency caused by ammonia water in mice (P < 0.001).

Metabolic profiling using combined GC–MS and LC–MS provides a systems understanding of aristolochic acid-induced nephrotoxicity in rat

Co-reporter:Yan Ni, Mingming Su, Yunping Qiu, Minjun Chen, ... Wei Jia

FEBS Letters (20 February 2007) Volume 581(Issue 4) pp:707-711

Publication Date(Web):20 February 2007

DOI:10.1016/j.febslet.2007.01.036

We present here a combined GC–MS and LC–MS metabolic profiling approach to unraveling the pathological outcomes of aristolochic acid (AA)-induced nephrotoxicity. Urine samples were analyzed by GC–MS and LC–MS in combination with pattern recognition techniques, e.g. principal component analysis (PCA), orthogonal projection to latent structure-discriminant analysis. The work indicates that AA-induced acute renal toxicity as evidenced by histopathological examinations could be characterized by systemic disturbance of metabolic network involving free fatty acids generation, energy and amino acids metabolism, and alteration in the structure of gut microbiota. Therefore, this method is potentially applicable to the toxicological study, providing a comprehensive understanding of systems response to xenobiotic intervention.