Metabolomics-Based Study of the Protective Effect of 4-Hydroxybenzyl Alcohol on Ischemic Astrocytes
Abstract
:1. Introduction
2. Results
2.1. Identification of ASs and Screening of 4HBA Safety and Efficacy in ASs
2.2. Effect of 4-HBA on CAT, MPTP, and Ca2+ Levels in ASs
2.3. Effect of 4HBA on ROS Content in ASs
2.4. Effect of 4HBA on Mitochondrial Morphology in ASs
2.5. Screening for Differential Metabolites in ASs
2.6. KEGG Enrichment of Metabolic Pathways
2.7. Metabolomic Validation in ASs
2.8. Effect of 4HBA on BBB Exudation in 2VO Rats
2.9. Effect of 4HBA on Brain Tissue and Mitochondria in 2VO Rats
2.10. Effect of 4HBA Connexin Protein in 2VO Rats
2.11. Effects of 4HBA on the Expression of GFAP, AQP4 and BDNF in 2VO Rats
2.12. Effect of 4HBA on NR1/NR2C-CREB-BNDF Pathway in 2VO Rats
3. Discussion
4. Materials and Methods
4.1. Animal
4.2. Drugs and Cell Culture Conditions
4.3. Extraction of Rat Cortical Primary ASs
4.4. Drug Administration and Model Replication in Groups
4.5. Cell Viability Assay for Drug Safety and Efficacy
4.6. Detection of Intracellular CAT, MPTP, and Ca2+ Content in ASs and Ca2+ Content in Mitochondria
4.7. Flow Cytometry to Detect Mitochondrial Membrane Potential
4.8. MitoTracker Red Staining to Measure Changes in Mitochondrial Morphology
4.9. MitoROS Levels Detected by Mitochondrial Superoxide Red Fluorescent Probe
4.10. Metabolomics Assay
4.11. BDNF Content in Culture Medium Was Detected
4.12. EB Experiment
4.13. HE Staining
4.14. Immunofluorescence Detection
4.15. Immunohistochemistry Assay
4.16. Electron Microscopy
4.17. Western Blotting
4.18. Statistics
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Compound | VIP | OGD/R vs. Control | 4HBA vs. OGD/R | p-Value | KEGG | ||
---|---|---|---|---|---|---|---|
FC | Change | FC | Change | ||||
Cycloserine | 1.346 | 44.196 | up | 0.146 | down | 0.005 | C08057 |
Betaine aldehyde | 1.413 | 5.5120 | up | 1.100 | up | 0.001 | C00576 |
D-Lactic acid | 1.813 | 5.083 | up | 1.402 | up | 0.000 | C00256 |
Beta-Sitosterol | 1.198 | 1.994 | up | 0.564 | down | 0.019 | C01753 |
Cyclic AMP | 1.683 | 1.837 | up | 2.863 | up | 0.022 | C00575 |
L-Phenylalanine | 1.441 | 1.722 | up | 1.405 | up | 0.021 | C00079 |
4-hydroxy-2H-chromen-2-one | 1.231 | 1.648 | up | 1.165 | up | 0.031 | C20414 |
Xanthurenic acid | 1.512 | 1.313 | up | 1.262 | up | 0.031 | C02470 |
(3S,4S)-3-hydroxytetradecane-1,3,4-tricarboxylic acid | 1.394 | 1.268 | up | 0.780 | down | 0.013 | C04529 |
Phosphocreatine | 1.841 | 1.070 | up | 1.355 | up | 0.012 | C02305 |
D-Ribulose 5-phosphate | 1.938 | 1.068 | up | 0.765 | down | 0.005 | C00199 |
2′-Deoxyinosine triphosphate | 1.608 | 1.064 | up | 1.531 | up | 0.039 | C01345 |
Azelaic acid | 1.844 | 1.015 | up | 0.771 | down | 0.008 | C08261 |
Aniline | 1.839 | 1.013 | up | 0.580 | down | 0.011 | C00292 |
16-Hydroxy hexadecanoic acid | 1.835 | 1.010 | up | 1.793 | up | 0.013 | C18218 |
Gamma-Tocopherol | 1.651 | 1.000 | down | 0.787 | down | 0.029 | C02483 |
Oxidized glutathione | 1.737 | 0.962 | down | 1.317 | up | 0.031 | C00127 |
Glutathione | 1.971 | 0.927 | down | 1.497 | up | 0.006 | C00051 |
Uridine diphosphate glucose | 1.675 | 0.907 | down | 1.438 | up | 0.042 | C00029 |
Hexadecanedioic acid | 1.376 | 0.905 | down | 0.899 | down | 0.035 | C19615 |
Cysteinylglycine | 2.091 | 0.872 | down | 1.645 | up | 0.002 | C01419 |
L-Glutamine | 1.377 | 0.508 | down | 1.839 | up | 0.006 | C00064 |
Spermine | 1.309 | 0.507 | down | 1.503 | up | 0.000 | C00750 |
5′-Methylthioadenosine | 1.252 | 0.496 | down | 1.464 | up | 0.000 | C00170 |
Cyclic AMP | 1.986 | 0.494 | down | 2.584 | up | 0.000 | C00575 |
Citicoline | 1.198 | 0.488 | down | 1.377 | up | 0.001 | C00307 |
Succinic acid | 1.163 | 0.486 | down | 1.531 | up | 0.004 | C00042 |
Uridine 5′-monophosphate | 1.321 | 0.483 | down | 1.643 | up | 0.000 | C00105 |
L-Tyrosine | 1.30 | 0.471 | down | 1.387 | up | 0.000 | C00082 |
L-Leucine | 1.292 | 0.466 | down | 1.480 | up | 0.000 | C00123 |
Albanin G | 1.341 | 0.453 | down | 1.781 | up | 0.001 | C10100 |
Creatinine | 1.242 | 0.437 | down | 1.400 | up | 0.000 | C00791 |
NADH | 1.244 | 0.434 | down | 2.133 | up | 0.026 | C00004 |
ADP | 1.493 | 0.431 | down | 2.078 | up | 0.001 | C00008 |
Spermidine | 1.455 | 0.423 | down | 2.030 | up | 0.000 | C00315 |
S-Adenosylhomocysteine | 1.047 | 0.423 | down | 1.269 | up | 0.010 | C00021 |
N-Acetylglutamic acid | 1.301 | 0.380 | down | 1.152 | up | 0.000 | C00624 |
Biotin | 1.299 | 0.319 | down | 2.100 | up | 0.000 | C00120 |
2′-Deoxyguanosine 5′-monophosphate | 1.368 | 0.303 | down | 2.427 | up | 0.000 | C00362 |
N-Acetylputrescine | 1.558 | 0.300 | down | 1.231 | up | 0.000 | C02714 |
Cytidine | 1.099 | 0.282 | down | 2.052 | up | 0.004 | C00475 |
Cycloserine | 1.346 | 44.196 | up | 0.146 | down | 0.005 | C08057 |
Betaine aldehyde | 1.413 | 5.5120 | up | 1.100 | up | 0.001 | C00576 |
D-Lactic acid | 1.813 | 5.083 | up | 1.402 | up | 0.000 | C00256 |
Beta-Sitosterol | 1.198 | 1.994 | up | 0.564 | down | 0.019 | C01753 |
Cyclic AMP | 1.683 | 1.837 | up | 2.863 | up | 0.022 | C00575 |
L-Phenylalanine | 1.441 | 1.722 | up | 1.405 | up | 0.021 | C00079 |
4-hydroxy-2H-chromen-2-one | 1.231 | 1.648 | up | 1.165 | up | 0.031 | C20414 |
Xanthurenic acid | 1.512 | 1.313 | up | 1.262 | up | 0.031 | C02470 |
(3S,4S)-3-hydroxytetradecane-1,3,4-tricarboxylic acid | 1.394 | 1.268 | up | 0.780 | down | 0.013 | C04529 |
Phosphocreatine | 1.841 | 1.070 | up | 1.355 | up | 0.012 | C02305 |
D-Ribulose 5-phosphate | 1.938 | 1.068 | up | 0.765 | down | 0.005 | C00199 |
2′-Deoxyinosine triphosphate | 1.608 | 1.064 | up | 1.531 | up | 0.039 | C01345 |
Azelaic acid | 1.844 | 1.015 | up | 0.771 | down | 0.008 | C08261 |
Aniline | 1.839 | 1.013 | up | 0.580 | down | 0.011 | C00292 |
16-Hydroxy hexadecanoic acid | 1.835 | 1.010 | up | 1.793 | up | 0.013 | C18218 |
Gamma-Tocopherol | 1.651 | 1.000 | down | 0.787 | down | 0.029 | C02483 |
Oxidized glutathione | 1.737 | 0.962 | down | 1.317 | up | 0.031 | C00127 |
Glutathione | 1.971 | 0.927 | down | 1.497 | up | 0.006 | C00051 |
Uridine diphosphate glucose | 1.675 | 0.907 | down | 1.438 | up | 0.042 | C00029 |
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Xiao, T.; Yu, X.; Tao, J.; Yang, L.; Duan, X. Metabolomics-Based Study of the Protective Effect of 4-Hydroxybenzyl Alcohol on Ischemic Astrocytes. Int. J. Mol. Sci. 2024, 25, 9907. https://doi.org/10.3390/ijms25189907
Xiao T, Yu X, Tao J, Yang L, Duan X. Metabolomics-Based Study of the Protective Effect of 4-Hydroxybenzyl Alcohol on Ischemic Astrocytes. International Journal of Molecular Sciences. 2024; 25(18):9907. https://doi.org/10.3390/ijms25189907
Chicago/Turabian StyleXiao, Tian, Xingzhi Yu, Jie Tao, Liping Yang, and Xiaohua Duan. 2024. "Metabolomics-Based Study of the Protective Effect of 4-Hydroxybenzyl Alcohol on Ischemic Astrocytes" International Journal of Molecular Sciences 25, no. 18: 9907. https://doi.org/10.3390/ijms25189907