Comparative Investigation of Raw and Processed Radix Polygoni Multiflori on the Treatment of Vascular Dementia by Liquid Chromatograph−Mass Spectrometry Based Metabolomic Approach
Abstract
:1. Introduction
2. Results
2.1. RPM and PPM Improved Memory Performance of VaD Rats
2.2. RPM and PPM Reduced the Histopathological Damage of VaD
2.3. RPM and PPM Exhibits Anti−Oxidant Effects
2.4. RPM and PPM Ameliorated Disordered Metabolism of VaD
2.5. Differential Metabolites in Treatment Group
2.6. Significant Pathways Shared by RPM and PPM Treatment Enriched by MSEA
2.7. Hallmarks Implicated in the Efficacy of RPM and PPM on the Treatment of VaD
2.8. Specifically Changed Metabolites and Associated Pathways by RPM and PPM
2.8.1. Determination of RPM and PPM Specific Metabolites
2.8.2. Significant Pathways Specific to RPM and PPM Treatment Enriched by MSEA
2.8.3. RPM and PPM Specific Mechanism in the Treatment of VaD
3. Discussion
4. Material and Methods
4.1. Drugs and Reagents
4.2. Preparation of PM Extracts
4.3. Animals and Experimental Procedure
4.4. Morris Water Maze Test
4.5. Sample Collection
4.6. Hematoxylin−Eosin and Nissl Staining
4.7. Oxidative Stress Indexes
4.8. Sample Preparation for LC−MS Analysis
4.9. LC−MS Analysis
4.10. Data Processing
4.11. Statistic Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
PM | Radix Polygoni Multiflori |
RPM | Raw Radix Polygoni Multiflori |
PPM | Processed Radix Polygoni Multiflori |
VaD | Vascular dementia |
AD | Alzheimer’s disease |
LC−MS | Liquid phase−tandem mass spectrometry |
HE | Hematoxylin−Eosin |
PCA | Principal component analysis |
PLSDA | Partial least squares discriminant analysis |
VIP | Variable Importance of Projection |
Hcy | Homocysteine |
MDA | Malondialdehyde |
SOD | Superoxide dismutase |
GSH | Glutathione |
PPP | Pentose phosphate pathways |
CV | Coefficients of variation |
SD | Sprague−Dawley |
2−VO | 2−vessel occlusion |
DG | Dentate gyrus |
CA | Cornu Ammonis |
MWM | Morris Water Maze Test |
BDNF | Brain−derived neurotrophic factor |
TCM | Traditional Chinese medicine |
DHAP | Dihydroxyacetone phosphate |
MSEA | Metabolite set enrichment analysis |
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Group | Path Length (m) | Time Spent in the Target Quadrant (%) | ||||
---|---|---|---|---|---|---|
Day 1 | Day 2 | Day 3 | Day 4 | Day 5 | ||
S | 15.99 ± 2.26 | 15.13 ± 2.66 | 3.32 ± 0.87 | 3.05 ± 0.69 | 7.33 ± 2.32 | 39.37 ± 3.01 |
M | 31.77 ± 3.13 ** | 26.49 ± 4.01 * | 15.82 ± 4.79 * | 6.02 ± 1.28 | 5.37 ± 1.15 | 23.43 ± 0.56 *** |
RPM | 16.32 ± 2.55 | 17.15 ± 4.89 | 9.33 ± 2.47 | 10.45 ± 2.09 | 5.15 ± 1.38 | 31.70 ± 3.85 |
PPM | 16.81 ± 3.38 | 13.64 ± 2.51 | 7.00 ± 1.99 | 9.26 ± 2.47 | 6.75 ± 1.68 | 26.92 ± 2.03 |
Group | Escape Latency (Second) | Average Velocity (cm/s) | Cross Platform Times | ||||
---|---|---|---|---|---|---|---|
Day 1 | Day 2 | Day 3 | Day 4 | Day 5 | |||
S | 61.31 ± 6.16 | 52.82 ± 12.03 | 18.62 ± 5.19 | 13.00 ± 2.60 | 18.06 ± 5.39 | 26.72 ± 1.44 | 121.2 ± 10.76 |
M | 104.8 ± 6.78 ** | 98.00 ± 9.54 * | 66.55 ± 15.83 *** | 24.05 ± 0.69 | 25.05 ± 3.16 | 29.35 ± 1.66 | 28.33 ± 2.29 *** |
RPM | 72.99 ± 11.99 | 74.21 ± 15.43 | 30.53 ± 8.08 | 35.47 ± 4.53 | 17.83 ± 3.28 | 28.26 ± 0.86 | 126.5 ± 17.09 ### |
PPM | 70.41 ± 12.21 | 66.41 ± 11.02 | 21.57 ± 4.33 | 30.19 ± 7.53 | 23.49 ± 5.30 | 29.23 ± 1.14 | 81.17 ± 5.54 ### |
Pathway Name | Matched Metabolites | Raw p (×10−3) | −log10(p) | FDR (×10−3) | Impact |
---|---|---|---|---|---|
Vitamin B6 metabolism | 2/9 | 0.010 | 4.984 | 0.116 | 0.745 |
beta−Alanine metabolism | 2/21 | 0.175 | 3.757 | 0.425 | 0.399 |
Glutathione metabolism | 3/28 | 0.660 | 3.180 | 1.403 | 0.351 |
Glycine, serine and threonine metabolism | 1/34 | 0.020 | 4.689 | 0.116 | 0.271 |
Pentose phosphate pathway | 3/21 | 0.095 | 4.024 | 0.292 | 0.208 |
Glyoxylate and dicarboxylate metabolism | 5/32 | 0.044 | 4.356 | 0.166 | 0.138 |
Citrate cycle (TCA cycle) | 2/20 | 0.106 | 3.975 | 0.300 | 0.135 |
Pyrimidine metabolism | 4/39 | 0.033 | 4.479 | 0.141 | 0.134 |
Tryptophan metabolism | 1/41 | 0.012 | 4.937 | 0.116 | 0.131 |
Tyrosine metabolism | 2/42 | 0.018 | 4.752 | 0.116 | 0.130 |
Alanine, aspartate and glutamate metabolism | 4/28 | 0.027 | 4.575 | 0.129 | 0.114 |
Glycerophospholipid metabolism | 3/36 | 1.114 | 2.953 | 2.229 | 0.113 |
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Wu, F.; Li, Y.; Liu, W.; Xiao, R.; Yao, B.; Gao, M.; Xu, D.; Wang, J. Comparative Investigation of Raw and Processed Radix Polygoni Multiflori on the Treatment of Vascular Dementia by Liquid Chromatograph−Mass Spectrometry Based Metabolomic Approach. Metabolites 2022, 12, 1297. https://doi.org/10.3390/metabo12121297
Wu F, Li Y, Liu W, Xiao R, Yao B, Gao M, Xu D, Wang J. Comparative Investigation of Raw and Processed Radix Polygoni Multiflori on the Treatment of Vascular Dementia by Liquid Chromatograph−Mass Spectrometry Based Metabolomic Approach. Metabolites. 2022; 12(12):1297. https://doi.org/10.3390/metabo12121297
Chicago/Turabian StyleWu, Fengye, Yunlin Li, Wenya Liu, Ran Xiao, Benxing Yao, Mingzhe Gao, Di Xu, and Junsong Wang. 2022. "Comparative Investigation of Raw and Processed Radix Polygoni Multiflori on the Treatment of Vascular Dementia by Liquid Chromatograph−Mass Spectrometry Based Metabolomic Approach" Metabolites 12, no. 12: 1297. https://doi.org/10.3390/metabo12121297
APA StyleWu, F., Li, Y., Liu, W., Xiao, R., Yao, B., Gao, M., Xu, D., & Wang, J. (2022). Comparative Investigation of Raw and Processed Radix Polygoni Multiflori on the Treatment of Vascular Dementia by Liquid Chromatograph−Mass Spectrometry Based Metabolomic Approach. Metabolites, 12(12), 1297. https://doi.org/10.3390/metabo12121297