Dataset Information

Differential annotation of converted metabolites (DAC-Met): Exploration of Maoto (Ma-huang-tang)-derived metabolites in plasma using high-resolution mass spectrometry.

ABSTRACT:

Introduction

Traditional herbal medicine (THM) contains a vast number of natural compounds with varying degrees of pharmacological activity. To elucidate the mode of action, comprehensive metabolite profiling in the plasma before and after administration of THM is essential.

Objective

The aim of this study was to explore and identify/annotate converted metabolites after administration of THM in humans.

Methods

We performed untargeted metabolome analysis of human plasma collected before and after administration of maoto (ma-huang-tang), a traditional Japanese Kampo medicine. Maoto-derived metabolites were then selected and annotated following the DAC-Met strategy, which is an annotation method that uses mass differences of major metabolic reactions among the detected peaks and a differential network analysis.

Results

About 80% of maoto-derived components were found to be converted forms. Following DAC-Met, the structures of 15 previously unidentified metabolites were determined, and five of these were later confirmed with authentic standards. Using published literature, we also reconstructed the metabolic pathway of maoto components in humans. A kinetic time-course analysis revealed their diverse kinetic profiles.

Conclusion

The results demonstrated that time-resolved comprehensive metabolite profiling in plasma using the DAC-Met strategy is highly useful for elucidating the complex nature of THM.

SUBMITTER: Ohbuchi K

PROVIDER: S-EPMC7183508 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Publications

Differential annotation of converted metabolites (DAC-Met): Exploration of Maoto (Ma-huang-tang)-derived metabolites in plasma using high-resolution mass spectrometry.

Ohbuchi Katsuya K Sakurai Nozomu N Kitagawa Hiroyuki H Sato Masaru M Suzuki Hideyuki H Kushida Hirotaka H Nishi Akinori A Yamamoto Masahiro M Hanazaki Kazuhiro K Arita Masanori M

Metabolomics : Official journal of the Metabolomic Society 20200425 5

<h4>Introduction</h4>Traditional herbal medicine (THM) contains a vast number of natural compounds with varying degrees of pharmacological activity. To elucidate the mode of action, comprehensive metabolite profiling in the plasma before and after administration of THM is essential.<h4>Objective</h4>The aim of this study was to explore and identify/annotate converted metabolites after administration of THM in humans.<h4>Methods</h4>We performed untargeted metabolome analysis of human plasma coll ...[more]

PMID: 32335721

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Project description:Although Ma Huang Tang (MHT) has long been considered as a classical formula for respiratory infections like influenza, bronchitis and asthma, its chemical ingredients that really exert the main efficacy are still obscure. In this study we aimed to screen its antiviral components and investigate the potential mechanisms. The MDCK cellular research results showed that, among nine predominant ingredients of MHT, L-methylephedrin (LMEP), L-ephedrine (LEP) and D-pseudo- ephedrine (DPEP) significantly inhibited the proliferation of influenza A virus in vitro, and the inhibitory effect at 24?h after the treatment was more obvious than that at 48?h. They also significantly inhibited the mRNA expression levels of related genes in the TLR3, TLR4 and TLR7 signaling pathways, which were accompanied with the down-regulation of TNF-? level and the up-regulation of IFN-? level in the cell supernatant. Therefore, three Ephedra alkaloids exert an antiviral effect in vitro which may be closely related to the inhibition of viral replication and the modulation of inflammatory response. Animal research further indicated, at the 3rd and 7th days after infection, LEP and DPEP significantly attenuated lung injury, decreased lung index, virus load in the lung and the level of IL-1? in serum, inhibited the mRNA expression levels of TNF-?, TLR3, TLR4, TLR7, MyD88, NF-?B p65 and RIG-1 as well as the protein expression levels of TLR4, TLR7, MyD88 and NF-?B p65 and markedly increased thymus index, the level of IL-10 in serum and the mRNA expression level of IFN-?. LEP and DPEP have certain protective effects on the influenza virus-infected mice, which may be associated with their abilities of effectively alleviating lung injury, improving the immunologic function of infected mice and adjusting the host's TLRs and RIG-1 pathways. The overall findings demonstrate that, as effective and inexpensive natural substances, Ephedra alkaloids and MHT may have potential utility in clinical management.

Project description:Glioblastoma multiforme (GBM) has a poor prognosis and its recurrence and mortality rates are high. At present, there is no effective clinical method to control its progression and recurrence. Traditional Chinese Medicine has a high status not only in China, but also in the world. Certain drugs are also used in the clinical treatment of tumor diseases. In clinical practice, Huang-Lian-Tang (HLT) has proven efficacy in treating brain diseases and preventing tumor recurrence. However, the mechanisms of action have remained elusive. The present study explored the potential mechanisms of HLT in the treatment of gliomas based on network pharmacology. First, information on the composition of HLT was obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and the composition and targets of the chemical substances contained in the herbs were analyzed. Subsequently, a pharmacological interaction network for HLT was built. Furthermore, the expressed genes of patients with GBM were obtained from Gene Expression Omnibus database and screened. A protein-protein interaction network was then constructed for both sets of data and they were combined with a topology method for analysis. Finally, the screened genes were subjected to enrichment analysis and pathway analysis. A total of 386 candidate targets and 7 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were screened, which were mainly associated with amino acid metabolism. Gene Ontology enrichment analysis and KEGG signal pathway analysis indicated that these targets are involved in anti-apoptosis, anti-oxidative stress, multicellular biological processes and other physiological and pathological processes related to the occurrence and development of GBM. In conclusion, the present results indicated that the mechanisms of action of HLT against GBM involve multiple targets and signaling pathways that are related to tumorigenesis and progression. The present study not only provided a novel theoretical basis for Traditional Chinese Medicine to treat tumors but also novel ideas for the treatment of GBM.

Dataset Information

Differential annotation of converted metabolites (DAC-Met): Exploration of Maoto (Ma-huang-tang)-derived metabolites in plasma using high-resolution mass spectrometry.

Introduction

Objective

Methods

Results

Conclusion

Publications

Differential annotation of converted metabolites (DAC-Met): Exploration of Maoto (Ma-huang-tang)-derived metabolites in plasma using high-resolution mass spectrometry.

Similar Datasets

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