Application of metabonomic analytical techniques in the modernization and toxicology research of traditional Chinese medicine

Abstract

In the recent years, a wide range of metabonomic analytical techniques are widely used in the modern research of traditional Chinese medicine (TCM). At the same time, the international community has attached increasing importance to TCM toxicity problems. Thus, many studies have been implemented to investigate the toxicity mechanisms of TCM. Among these studies, many metabonomic-based methods have been implemented to facilitate TCM toxicity investigation. At present, the most prevailing methods for TCM toxicity research are mainly single analysis techniques using only one analytical means. These techniques include nuclear magnetic resonance (NMR), gas chromatography-mass spectrometry (GC-MS), and liquid chromatography-mass spectrometry (LC-MS), etc.; with these techniques, some favourable outcomes have been gained in the toxic reaction studies of TCM, such as the action target organs assay, the establishment of action pattern, the elucidation of action mechanism and the exploration of action material foundation. However, every analytical technique has its advantages and drawbacks, no existing analytical technique can be versatile. Multi-analysed techniques can partially overcome the shortcomings of single-analysed techniques. Combination of GC-MS and LC-MS metabolic profiling approaches has unravelled the pathological outcomes of aristolochic acid-induced nephrotoxicity, which can not be achieved by single-analysed techniques. It is believed that with the further development of metabonomic analytical techniques, especially multi-analysed techniques, metabonomics will greatly promote TCM toxicity research and be beneficial to the modernization of TCM in terms of extending the application of modern means in the TCM safety assessment, assisting the formulation of TCM safety norms and establishing the international standards indicators.

Figure 1

Number of metabonomics-related papers published between January 2000 and December 2007. Generally, metabonomics is gaining more and more attention as showed by the number of related papers published by several main international well-known academic databases. Databases are searched using ISI Web of sciencedirect (site 1), interscience (site 2), acs (site 3) and ebscohost (site 4). Search term used was: ‘metabolomic or metabolomics or metabonomic or metabonomics or metabolite profiling’.

Figure 2

Flow chart of the metabonomic investigation in TCM toxicity research. GC, gas chromatography; HPLC, high-performance liquid chromatography; MS, mass spectrometry; NMR, nuclear magnetic resonance; TCm, traditional Chinese medicine; UPLC, ultra high-performance liquid chromatography.

Figure 3

The perturbed metabolic pathways in response to aristolochic acid (AA) exposure (modified from Ni et al., 2007): (A) AA-induced metabolic disorder of amino acids; (B) AA perturbed tricarboxylic acids (TCA) cycle; (C) PLA2-related mechanisms of AA-induced nephrotoxicity. Dark square denotes an elevated concentration of metabolites present in the urine from rats exposed to AA, whereas gray square means a reduced level of metabolites in this group as compared to the healthy. The red abbreviations adjacent to the arrows are consistent with the corresponding enzymes, in detail, AH: aconitate hydratase; CBL: cystathionine beta-lyase; CBS: cystathionine beta-synthase; CGS: cystathionine gamma-synthase; CSY: citrate (Si)-synthase; CTL: cystathionine gamma-lyase; CysR: cystine reductase; Fum: fumarate hydratase; GNMT: glycine N-methyltransferase; G-SCS: succinate–CoA ligase (GDP-forming); HMT: homocysteine S-methyltransferase; ICDH: isocitrate dehydrogenase (NADP(+)); MAT: methionine adenosyltransferase; MDH: malate dehydrogenase; MetE: 5-methyltetrahydropteroyltriglutamate–homocysteine S-methyltransferase; SAHH: adenosylhomocysteinase; SDH: succinate dehydrogenase (ubiquinone).