Comprehensive TCM molecular networking based on MS/MS in silico spectra with integration of virtual screening and affinity MS screening for discovering functional ligands from natural herbs

Wang, Zhihua; Kim, Unchol; Liu, Jinbiao; Cheng, Chuanjing; Wu, Wenbo; Guo, Shuang; Ying, Feng; Quinn, Ronald J.; Hou, Yuanyuan; Bai, Gang

doi:10.1007/s00216-019-01962-4

Cited by 29 publications

(16 citation statements)

References 30 publications

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“…In contrast to classic NSAIDs, few COX-1/2 inhibitors have been identified in commonly used clinical antipyretic herbs. Owing to the large number of compounds in the herbs and limited information about the huge regulatory network, accurately determining the most bioactive compound, its target, as well as the mechanism of action, remains challenging [21].…”

Section: Discussionmentioning

confidence: 99%

Mechanism Assay of Honeysuckle for Heat-Clearing Based on Metabolites and Metabolomics

Wang

Han

et al. 2022

Metabolites

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Nonsteroidal anti-inflammatory drugs (NSAIDs), such as cyclooxygenase (Cox)-1/2 inhibitor, have emerged as potent antipyretics and analgesics. However, few herbs with Cox-1/2 inhibitory activity are commonly used for heat-clearing in China. Although these are known to have antipyretic activity, there is a lack of molecular data supporting their activity. Using the traditional Chinese medicine herb honeysuckle (Hon) as an example, we explored key antipyretic active compounds and their mechanisms of action by assessing their metabolites and metabolomics. Mitogen-activated protein kinase (MAPK) 3 and protein kinase B (AKT) 1 were suggested as key targets regulated primarily by chlorogenic acid (CA) and swertiamarin (SWE). CA and SWE synergistically inhibited the production of interleukin (IL)-1 and IL-6, alleviated generation of prostaglandin E2, and played an antipyretic role equivalent to honeysuckle extract at the same dose contents within 3 h. Collectively, these findings indicated that lipopolysaccharide-induced fever can be countered by CA with SWE synergistically, allowing the substitution of a crude extract of complex composition with active compounds. Our findings demonstrated that, unlike the traditional NSAIDs, the Hon extract showed a remote and indirect mechanism for alleviating fever that depended on the phosphatidylinositol-3-kinase–AKT and MAPK pathways by regulating the principal mediator of inflammation.

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Section: Discussionmentioning

confidence: 99%

Mechanism Assay of Honeysuckle for Heat-Clearing Based on Metabolites and Metabolomics

Wang

Han

et al. 2022

Metabolites

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“…To our knowledge, this study is the first to explore the potentialities of FBMN for documenting the detailed composition of a TCM multiherb formula. Molecular networking was previously successfully used to annotate components of interest in single TCM herb extracts (Pan et al, 2019;Wang et al, 2019;Wang et al, 2020b).…”

Section: Feature-based Molecular Network For Multi-herb Formulae Compmentioning

confidence: 99%

“…Furthermore, organizing HRMS/MS data by molecular networking (MN) brought a novel dimension to metabolite annotation (Wang et al, 2016a). As a way of classifying structurally related chemicals, MN is seen as a tool of interest for TCMs chemical investigation (Hou et al, 2019) and has recently begun to be employed in TCM research to annotate single herb extracts (Pan et al, 2019;Wang et al, 2019;Wang et al, 2020b). Data processing step by open-source software, such as MZmine (Pluskal et al, 2010) prior to MN has enabled the generation of so-called feature-based molecular networks (FBMN) (Nothias et al, 2020) (Table 1).…”

Section: Introductionmentioning

confidence: 99%

A Mass Spectrometry Based Metabolite Profiling Workflow for Selecting Abundant Specific Markers and Their Structurally Related Multi-Component Signatures in Traditional Chinese Medicine Multi‐Herb Formulae

et al. 2020

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In Traditional Chinese Medicine (TCM), herbal preparations often consist of a mixture of herbs. Their quality control is challenging because every single herb contains hundreds of components (secondary metabolites). A typical 10 herb TCM formula was selected to develop an innovative strategy for its comprehensive chemical characterization and to study the specific contribution of each herb to the formula in an exploratory manner. Metabolite profiling of the TCM formula and the extract of each single herb were acquired with liquid chromatography coupled to high-resolution mass spectrometry for qualitative analyses, and to evaporative light scattering detection (ELSD) for semi-quantitative evaluation. The acquired data were organized as a feature-based molecular network (FBMN) which provided a comprehensive view of all types of secondary metabolites and their occurrence in the formula and all single herbs. These features were annotated by combining MS/MS-based in silico spectral match, manual evaluation of the structural consistency in the FBMN clusters, and taxonomy information. ELSD detection was used as a filter to select the most abundant features. At least one marker per herb was highlighted based on its specificity and abundance. A single large-scale fractionation from the enriched formula enabled the isolation and formal identification of most of them. The obtained markers allowed an improved annotation of associated features by manually propagating this information through the FBMN. These data were incorporated in the high-resolution metabolite profiling of the formula, which highlighted specific series of related components to each individual herb markers. These series of components, named multi-component signatures, may serve to improve the traceability of each herb in the formula. Altogether, the strategy provided highly informative compositional data of the TCM formula and detailed visualizations of the contribution of each herb by FBMN, filtered feature maps, and reconstituted chromatogram traces of all components linked to each specific marker. This comprehensive MS-based analytical workflow allowed a generic and unbiased selection of specific and abundant markers and the identification of multiple related sub-markers. This exploratory approach could serve as a starting point to develop more simple and targeted quality control methods with adapted marker specificity selection criteria to given TCM formula.

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“…It is usually needed to integrate other methods to find out the active ingredients. Affinity MS has reported MN technology's successful application in detecting and separating active compounds (Wang et al., 2019). The use of MN in natural products produced by marine Vibrio species has led to the discovery of a series of antibacterial aminopolyketone derivatives as well as anti‐inflammatory and analgesic Spongonucleosides (Bertin et al., 2015; Kleigrewe et al., 2015; Liaw et al., 2015).…”

Section: Introductionmentioning

confidence: 99%

Integrated molecular network and HPLC‐UV‐FLD analysis to explore antioxidant ingredients in camellia nitidissima Chi

Cheng

Hou

Hao

et al. 2021

Journal of Food Science

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At present, screening of active ingredients from natural products for pharmacological and clinical research is mostly time-consuming and costly. In this study, a molecular network (MN) guided high performance liquid chromatography-ultraviolet-fluorescence detector (HPLC-UV-FLD) method was carried out to profile the global antioxidant activity compounds, including the trace amount ingredients in Camellia nitidissima Chi (CNC). Firstly, HPLC-UV-FLD postcolumn derivatization system was utilized to screen the antioxidants. Then the MN of CNC was established via mass spectrometry (MS) data for getting the connection between ingredient structures. As a result, HPLC-UV-FLD indicated three antioxidant ingredients: gallic acid (126.3 mg/g), catechin (564.8 mg/g), and salicylic acid (24.3 mg/g). Combined with the MN, the actives' precise location and connection relationship were clarified based on the structural similarities. A new antioxidant ingredient, okicamelliaside, was suggested and evaluated at free radical scavenging and enzymatic protection. The novel method of activity and structural correlation analysis based on MN could provide a useful guide for screening trace active ingredients in natural products.Practical Application: Three main ingredients were screened out from Camellia nitidissima Chi by HPLC-UV-FLD postcolumn derivatization system. Integrated molecular network and HPLC-UV-FLD analysis, a new type of antioxidant okicamelliaside was selected. The novel method of activity and structural correlation analysis based on molecular network could provide a useful guide for screening trace active ingredients in natural products.

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Comprehensive TCM molecular networking based on MS/MS in silico spectra with integration of virtual screening and affinity MS screening for discovering functional ligands from natural herbs

Cited by 29 publications

References 30 publications

Mechanism Assay of Honeysuckle for Heat-Clearing Based on Metabolites and Metabolomics

Mechanism Assay of Honeysuckle for Heat-Clearing Based on Metabolites and Metabolomics

A Mass Spectrometry Based Metabolite Profiling Workflow for Selecting Abundant Specific Markers and Their Structurally Related Multi-Component Signatures in Traditional Chinese Medicine Multi‐Herb Formulae

Integrated molecular network and HPLC‐UV‐FLD analysis to explore antioxidant ingredients in camellia nitidissima Chi

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