PUBLICATION
Anti-Hypoxic Molecular Mechanisms of Rhodiola crenulata Extract in Zebrafish as Revealed by Metabonomics
- Authors
- Ma, Y., Wu, Y., Xia, Z., Li, J., Li, X., Xu, P., Zhou, X., Xue, M.
- ID
- ZDB-PUB-191130-13
- Date
- 2019
- Source
- Frontiers in pharmacology 10: 1356 (Journal)
- Registered Authors
- Keywords
- Rhodiola crenulata, anti-hypoxia, metabonomics, network analysis, zebrafish
- MeSH Terms
- none
- PubMed
- 31780949 Full text @ Front Pharmacol
Citation
Ma, Y., Wu, Y., Xia, Z., Li, J., Li, X., Xu, P., Zhou, X., Xue, M. (2019) Anti-Hypoxic Molecular Mechanisms of Rhodiola crenulata Extract in Zebrafish as Revealed by Metabonomics. Frontiers in pharmacology. 10:1356.
Abstract
The health supplement of Rhodiola crenulata (RC) is well known for its effective properties against hypoxia. However, the mechanisms of its anti-hypoxic action were still unclear. The objective of this work was to evaluate the molecular mechanisms of RC extract against hypoxia in a hypoxic zebrafish model through metabonomics and network pharmacology analysis. The hypoxic zebrafish model in the environment with low concentration (3%) of oxygen was constructed and used to explore the anti-hypoxic effects of RC extract, followed by detecting the changes of the metabolome in the brain through liquid chromatography-high resolution mass spectrometry. An in silico network for metabolite-protein interactions was further established to examine the potential mechanisms of RC extract, and the mRNA expression levels of the key nodes were validated by real-time quantitative PCR. As results, RC extract could keep zebrafish survive after 72-h hypoxia via improving lactate dehydrogenase, citrate synthase, and hypoxia-induced factor-1α in brains. One hundred and forty-two differential metabolites were screened in the metabonomics, and sphingolipid metabolism pathway was significantly regulated after RC treatment. The constructed protein-metabolites network indicated that the HIF-related signals were recovered, and the mRNA level of AMPK was elevated. In conclusion, RC extract had markedly anti-hypoxic effects in zebrafish via changing sphingolipid metabolism, HIF-related and AMPK signaling pathways.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping