Influence of Chromatogram Baseline Shifts and Exogenous Metabolite Signals on Metabolic Profiles of Traditional Chinese Medicine Chaihu and Its Liver Toxicity Metabonomics

doi:10.1007/s40242-017-6302-z

Chemical Research in Chinese Universities ›› 2017, Vol. 33 ›› Issue (1): 17-23.doi: 10.1007/s40242-017-6302-z

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Influence of Chromatogram Baseline Shifts and Exogenous Metabolite Signals on Metabolic Profiles of Traditional Chinese Medicine Chaihu and Its Liver Toxicity Metabonomics

ZENG Qi¹, FENG Jiangjiang¹, LÜ Tian¹, XU Liangyu¹, MIN Chunyan^1,2, XIE Hongping¹

1. College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, P. R. China;
2. Suzhou Institute for Food and Drug Control, Suzhou 215104, P. R. China

Received:2016-07-14 Revised:2016-09-20 Online:2017-02-01 Published:2016-11-28
Contact: XIE Hongping,E-mail:hpxie@suda.edu.cn;MIN Chunyan,E-mail:minchunyan0609@hotmail.com E-mail:hpxie@suda.edu.cn;minchunyan0609@hotmail.com
Supported by:
Supported by the National Natural Science Foundation of China(No.81001686) and the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions, China.

Abstract

Abstract:

In an LC-MS investigation of drug metabolic samples from the traditional Chinese medicine Chaihu, the baseline was established via MS selectivity-based chromatogram baseline-shift elimination and exogenous metabolite signals were obtained with MS-based orthogonal projection. Their respective influences on the metabolic chromatographic profiles, metabonomics model and evaluation of drug toxicity were investigated. The baseline shift enhanced the difference between the metabolic profiles of the control and Chaihu groups, and the corresponding correlation coefficient decreased from 70.38% to 62.69%. The exogenous metabolite signal led to a biased expression of the evaluated toxicity, and the enhanced expression resulted in an average Mahalanobis distance of approximately 9.4%. Based on established metabonomics models, the results show that Chaihu induces liver toxicity at a lower dose of 25 g/kg, twice a day. At this dose, Chaihu elicits a process of self-repair for its liver toxicity. The signal intensities of exogenous metabolites from Chaihu changed with the administration time, but only the signal intensities of large molecule metabolites(m/z 500-850) from Chaihu had a positive correlation with its toxicity. These results suggest that liver toxicity from low doses of Chaihu was probably caused by the larger molecule components and not by its active components, saikosaponin and flavonoid glycoside.

Key words: Exogenous metabolite signal, Chromatogram baseline shift, Metabolic profile, Metabonomics, Liver toxicity, Chaihu

ZENG Qi, FENG Jiangjiang, LÜ Tian, XU Liangyu, MIN Chunyan, XIE Hongping. Influence of Chromatogram Baseline Shifts and Exogenous Metabolite Signals on Metabolic Profiles of Traditional Chinese Medicine Chaihu and Its Liver Toxicity Metabonomics[J]. Chemical Research in Chinese Universities, 2017, 33(1): 17-23.

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Influence of Chromatogram Baseline Shifts and Exogenous Metabolite Signals on Metabolic Profiles of Traditional Chinese Medicine Chaihu and Its Liver Toxicity Metabonomics

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