PUBLICATION
Discovery and identification of antithrombotic chemical markers in gardenia fructus by herbal metabolomics and zebrafish model
- Authors
- Shi, Y.P., Zhang, Y.G., Li, H.N., Kong, H.T., Zhang, S.S., Zhang, X.M., Li, X.B., Liu, K.C., Han, L.W., Tian, Q.P.
- ID
- ZDB-PUB-200227-5
- Date
- 2020
- Source
- Journal of ethnopharmacology 253: 112679 (Journal)
- Registered Authors
- Keywords
- Antithrombosis, Bioactivity markers, Gardenia fructus, Grey correlation analysis, Herbal metabolomics, Zebrafish
- MeSH Terms
-
- Animals
- Biomarkers/metabolism
- Disease Models, Animal
- Embryo, Nonmammalian
- Female
- Fibrinolytic Agents/chemistry
- Fibrinolytic Agents/pharmacology
- Fibrinolytic Agents/therapeutic use*
- Fruit
- Gardenia*
- Male
- Metabolomics
- Phytochemicals/analysis
- Phytochemicals/pharmacology
- Phytochemicals/therapeutic use
- Plant Extracts/chemistry
- Plant Extracts/pharmacology
- Plant Extracts/therapeutic use*
- Protein Interaction Maps
- Thrombosis/drug therapy*
- Thrombosis/metabolism
- Zebrafish
- PubMed
- 32101773 Full text @ J. Ethnopharmacol.
Citation
Shi, Y.P., Zhang, Y.G., Li, H.N., Kong, H.T., Zhang, S.S., Zhang, X.M., Li, X.B., Liu, K.C., Han, L.W., Tian, Q.P. (2020) Discovery and identification of antithrombotic chemical markers in gardenia fructus by herbal metabolomics and zebrafish model. Journal of ethnopharmacology. 253:112679.
Abstract
Ethnopharmacological relevance Gardenia Fructus (GF), a traditional Chinese medicine for clearing heat and purging fire, has been reported to use to treat thrombotic related diseases, but the antithrombotic components are not clear.
Aim of the study To develop efficient research methods for discovering some representative antithrombotic compounds of GF.
Materials and methods AB line zebrafish induced by arachidonic acid (AA) was used as a fast and trace-sample-required valuation model for GF samples of antithrombotic effects. Among nine samples of GF from different production areas, two samples with the largest difference in bioactivity were selected for downstream analysis. High-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF/MS) was applied to detect compounds in the GF samples. And Herbal metabolomics and Grey correlation analysis (GCA) were used to identify crucial compounds with potential antithrombotic activity. Then the bioactivity of those important compounds was verified on the zebrafish model. Network pharmacology was used to explore the protein targets and signaling pathways of these compounds.
Results Among the GF samples, S1 (Huoshan City, Anhui Province), and S6 (Jichun City, Hubei Province), significantly differed in thrombus inhibiting bioactivity. HPLC-Q-TOF/MS identified a total of 614 compounds in each GF sample. 19 compounds were selected as important potential variables from metabolomics data by orthogonal partial least squares discriminant analysis (OPLS-DA). And 10 compounds among them were further found to be positively correlated with the antithrombotic bioactivity of GF by GCA. Finally, 3 compounds in them, geniposide, citric acid, and quinic acid, were confirmed as representative antithrombotic chemical markers of GF. Using network pharmacology analysis, some key protein targets, such as proto-oncogene tyrosine-protein kinase Src (SRC) and cyclin-dependent kinase 2 (CDK2), and some signaling pathways were found to supply powerful evidence about antithrombotic mechanisms of three compounds and GF.
Conclusions This research have succeeded to discover and identify three representative antithrombotic compounds of GF using an efficient integrated research strategy we established, an Omics Discriminant-Grey Correlation-Biological Activity strategy. The antithrombotic chemical makers we found could also contribute to provided more accurate index components for comprehensive quality control of GF.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping