Advanced applications of mass spectrometry imaging technology in quality control and safety assessments of traditional Chinese medicines

Abstract

Ethnopharmacological relevance: Traditional Chinese medicines (TCMs) have made great contributions to the prevention and treatment of human diseases in China, and especially in cases of COVID-19. However, due to quality problems, the lack of standards, and the diversity of dosage forms, adverse reactions to TCMs often occur. Moreover, the composition of TCMs makes them extremely challenging to extract and isolate, complicating studies of toxicity mechanisms.

Aim of the review: The aim of this paper is therefore to summarize the advanced applications of mass spectrometry imaging (MSI) technology in the quality control, safety evaluations, and determination of toxicity mechanisms of TCMs.

Materials and methods: Relevant studies from the literature have been collected from scientific databases, such as "PubMed", "Scifinder", "Elsevier", "Google Scholar" using the keywords "MSI", "traditional Chinese medicines", "quality control", "metabolomics", and "mechanism".

Results: MSI is a new analytical imaging technology that can detect and image the metabolic changes of multiple components of TCMs in plants and animals in a high throughput manner. Compared to other chemical analysis methods, such as liquid chromatography-mass spectrometry (LC-MS), this method does not require the complex extraction and separation of TCMs, and is fast, has high sensitivity, is label-free, and can be performed in high-throughput. Combined with chemometrics methods, MSI can be quickly and easily used for quality screening of TCMs. In addition, this technology can be used to further focus on potential biomarkers and explore the therapeutic/toxic mechanisms of TCMs.

Conclusions: As a new type of analysis method, MSI has unique advantages to metabolic analysis, quality control, and mechanisms of action explorations of TCMs, and contributes to the establishment of quality standards to explore the safety and toxicology of TCMs.

Keywords: MSI; Pharmacology and toxicology; Quality control; Spatial metabolomics; TCMs.

Graphical abstract

Fig. 1

The Experimental process of MALDI-MSI (kidney).

Fig. 2

MSI results from Putterlickia pyracantha stems (Eckelmann et al., 2016). A. Chemical structures of maytansinoids occurring in Putterlickia pyracantha. B. (a) Anatomical imaging of the cross section of Putterlickia pyracantha stems stained with phloroglucinol/HCL. (b–d) MALDI-imaging-HRMS of different Putterlickia pyracantha stem cuttings (spatial resolution: 40 μm; scan area: b: 3720 × 2600 μm; c: 3520 × 4120 μm; d: 3720 × 2600 μm). Localization of maytansine ([M+K]⁺; m/z 730.2503), maytanprine ([M+K]⁺; m/z 744.2659), maytanbutine ([M+K] ⁺; m/z 758.2816), maytansine precursor 6 ([M+K] ⁺; m/z 716.2347), maytanvaline ([M+K]⁺; m/z 772.2973), normaytancyprine ([M+K]⁺; m/z 770.2816), maytansine ([M+K]⁺; m/z 730.2503), hydroxylated maytansine ([M+K]⁺; m/z 746.2452), and hydroxylated maytanprine ([M+K]⁺; m/z 760.2609).

Fig. 3

MALDI-MSI distinguishing ginseng of different ages based on the localization of ginsenosides (Bai et al., 2016) A. (a) Optical scan image of ginseng. (b) Overlay of ion images: red, m/z 805.5 (Rg8/Rk/Rz₁); yellow, m/z 955.6 (unidentified); blue, m/z 917.8 (unidentified). (c–g) Five localization modes of signals: xylem-medulla type (c1 and c2); xylem-only type (d1 and d2); cork-xylem type (e1 and e2); cork-phloem-cambium-medulla type (f1 and f2); and cork-only type (g1 and g2). B. PCA score plot and 2D peak distribution plot of m/z 1117.5 and m/z 1147.5: a and c, whole tissue; b and d, cork. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

Fig. 4

Spatially resolved metabolomics based on MSI to elucidate the pharmacodynamic mechanisms of NG-R1 (Zhu et al., 2020). The rats in this study were divided into four groups: Sham, MCAO/R, NG-R1 (20 mg/kg, 7 days), and NBP (20 mg/kg, 7 days). Pharmacodynamic studies (included neurological score, TTC staining, histopathology staining, immunofluorescence staining, and TUNEL staining) conducted 7 days after ischemic-reperfusion showed that NG-R1 can reduce infarction volumes and neurologic deficits in MCAO/R rats and attenuate neuronal loss 7 d after MCAO/R surgery, while also inhibiting neuronal apoptosis and astrocyte activation. To clarify the mechanisms by which those events occur, the study further used spatially resolved metabolomics based on MALDI-MSI and found that NG-R1 can regulate the abnormal accumulation of glucose and citric acid, increase the content of glutamate and malate-aspartic acid shuttle components, increase antioxidant content, increase ATP metabolism, and maintain the homeostasis of Na⁺ and K⁺ to achieve anti-ischemia/reperfusion injury effects.