Mass spectrometry-based metabolomic as a powerful tool to unravel the component and mechanism in TCM

Abstract

Mass spectrometry (MS)-based metabolomics has emerged as a transformative tool to unraveling components and their mechanisms in traditional Chinese medicine (TCM). The integration of advanced analytical platforms, such as LC-MS and GC-MS, coupled with metabolomics, has propelled the qualitative and quantitative characterization of TCM's complex components. This review comprehensively examines the applications of MS-based metabolomics in elucidating TCM efficacy, spanning chemical composition analysis, molecular target identification, mechanism-of-action studies, and syndrome differentiation. Recent innovations in functional metabolomics, spatial metabolomics, single-cell metabolomics, and metabolic flux analysis have further expanded TCM research horizons. Artificial intelligence (AI) and bioinformatics integration offer promising avenues for overcoming analytical bottlenecks, enhancing database standardization, and driving interdisciplinary breakthroughs. However, challenges remain, including the need for improved data processing standardization, database expansion, and understanding of metabolite-gene-protein interactions. By addressing these gaps, metabolomics can bridge traditional practices and modern biomedical research, fostering global acceptance of TCM. This review highlights the synergy of advanced MS techniques, computational tools, and TCM's holistic philosophy, presenting a forward-looking perspective on its clinical translation and internationalization.

Keywords: Component analysis; Mass spectrometry; Mechanism; Metabolomics; Traditional Chinese medicine.

Fig. 1

Frame of MS-based metabolomic for TCM. The exploration of TCMs and its pharmacological effects through metabolomics technology utilizing MS [1, 3, 12]

Fig. 2

General overview and schematic content of MS-based metabolomics workflow [–16]

Fig. 3

Recommended chromatography-based analysis methods of various molecular features [33]

Fig. 4

Data acquisition modes of MS. Schematic workflow A and the comparison B of full-scan, DDA, and DIA modes [69], timeline of developments of DIA approaches used in MS analysis C. The time for different DIA acquisition schemes, traditional method (orange), SWATH (green), SWATH-based method (purple), 4-dimension method (blue) [–72]

Fig. 5

Workflows of metabolomics. A Non-targeted and targeted metabolomics strategy for identification of TCM [79]. B An updated functional metabolomics in the modern exploration of TCM derived functional compounds [3]. C General overview of spatial metabolomics workflow [80]. D Schematics of SCM [57]. E Integrative metabolic flux analysis of various quantitative techniques [81]

Fig. 6

MS-based metabolomic applications under different conditions in TCM. A Using a tandem multi-stage MS platform and a “top-down” strategy comprehensively characterize the saponin compounds in Panax notoginseng [116]. B Therapeutic effects, the potential target and mechanism of CSR on treating ulcerative colitis using untargeted metabolomics, histological staining, intestinal permeability assay et al. [117]. C By applying metabolomics, transcriptomics, and proteomics to study the mutant K13 protect Plasmodium falciparum against the effects of artemisinin [118]. D Using MS-based metabolomics technology, researchers aim to identify biomarkers for two syndromes (phlegm-stasis syndrome and qi-yin deficiency syndrome) in coronary heart disease patients [119]