Amelioration of Alcoholic Liver Disease by Activating PXR-Cytochrome P450s Axis with Blackberry Extract
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials and Reagents
2.2. Preparation of the Blackberry Extract
2.3. Polyphenol, Flavonoids, and Anthocyanin Contents
2.4. Antioxidant Activities
2.5. Animals and Treatment
2.5.1. Animals
2.5.2. Experimental Design
2.5.3. Measurement of Related Indices
2.5.4. Histopathological Observation
2.5.5. Network Pharmacological Analysis of Cyanidin-3-O-glucoside
2.5.6. Establishment of PPI Network
2.5.7. Analysis of Target Pathways
2.5.8. Construction of Regulatory Network for Cyanidin-3-O-glucoside-Targets-Pathways-Disease
2.5.9. Analysis of Gene Ontology and KEGG
2.5.10. In Silico Molecular Docking Study
2.5.11. qRT-PCR Analysis
2.6. Potential Mechanisms of BBE against HepG2 Cells
2.6.1. Cell Viability Assay
2.6.2. Detection of Apoptosis by Flow Cytometry in HepG2 Cells
2.6.3. Measurement of Mitochondrial Membrane Potential in HepG2 Cells
2.6.4. Detection of ROS Levels in HepG2 Cells
2.7. Western Blotting
2.8. Data and Statistical Analysis
3. Results
3.1. The Contents of Polyphenols, Flavonoids, and Anthocyanins
3.2. Antioxidant Activities
3.3. Measurement of Related Indices
3.4. Histopathological Observation
3.5. Network Pharmacological Analysis of Cyanidin-3-O-glucoside
3.6. Establishment of PPI Network
3.7. Analysis of Target Pathways
3.8. Construction of Regulatory Network for Cyanidin-3-O-glucoside-Targets-Pathways-Disease
3.9. In Silico Molecular Docking Study
3.10. qRT-PCR Analysis
3.11. Detection of Apoptosis by Flow Cytometry in HepG2 Cells
3.12. Measurement of Mitochondrial Membrane Potential in HepG2 Cells
3.13. Detection of ROS Levels in HepG2 cells
3.14. Western Blotting
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
References
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Gene | Forward (5′-3′) | Reverse (5′-3′) |
---|---|---|
PXR | AGACGGCAGCATCTGGAACTAC | GTTTCTGGAAGCCACCATTAGG |
CAR | CCACAGGCTATCATTTCCACG | CCTTCCAGCAAACGGACAGAT |
CYP3A25 | GGAGGCCTGAACTGCTAAAG | GTAGTTGAAAATGGTGCCAAGTAAC |
CYP3A11 | GGTGCTCCTAGCAATCAGCTT | AAGGAGAGGCGTTTGACCATC |
CYP2B10 | TCTGCCCTTCTCAACAGGAAAG | AAGGAGAGGCGTTTGACCATC |
GAPDH | TTGGAGCCCTGGAGATTTGGA | TGAGGTCAATGAAGGGGTCGT |
Species | TP a | TF b | TMA c | DPPH d | ABTS d | FRAP e |
---|---|---|---|---|---|---|
Blackberry | 5.70 ± 1.34 | 105.70 ± 12.11 | 24.50 ± 3.49 | 22.08 ± 7.13 | 51.69 ± 7.84 | 2.93 |
Vc | 4.76 ± 1.15 | 36.23 ± 5.78 | 1 |
Treatment Group | Final Weight (g) | Liver Index (%) | AST (U/L) | ALT (U/L) | SOD (U/mL) | MDA (U/mL) |
---|---|---|---|---|---|---|
(a) Subacute ALD mice | ||||||
Control | 41.45 ± 2.78 | 4.23 ± 0.24 | 135.60 ± 8.75 | 55.07 ± 7.03 | 260.13 ± 17.52 | 5.76 ± 0.24 |
Model | 34.48 ± 3.45 | 3.76 ± 0.31 | 189.92 ± 15.87 *** | 94.08 ± 1.55 *** | 177.88 ± 3.24 *** | 11.37 ± 0.14 |
Low-dose BBE | 36.69 ± 4.05 | 3.81 ± 0.55 | 169.60 ± 11.35 ### | 82.01 ± 1.09 ### | 191.01 ± 2.89 ### | 8.79 ± 0.24 ### |
Medium-dose BBE | 35.87 ± 3.61 | 3.71 ± 0.39 | 163.73 ± 10.24 ### | 72.28 ± 2.23 ### | 229.02 ± 6.96 ### | 8.19 ± 0.65 ### |
High-dose BBE | 36.12 ± 3.34 | 3.69 ± 0.25 | 151.18 ± 5.27 ### | 61.57 ± 3.97 ### | 235.07 ± 3.15 ### | 8.03 ± 0.42 ### |
(b) Acute ALD mice | ||||||
Control | 40.90 ± 0.45 | 3.29 ± 0.30 | 121.14 ± 9.95 | 44.71 ± 7.13 | 306.80 ± 17.14 | 6.37 ± 0.42 |
Model | 41.00 ± 0.31 | 4.30 ± 0.21 | 210.14 ± 22.60 | 72.65 ± 0.55 | 231.62 ± 4.29 | 8.94 ± 0.21 |
Low-dose BBE | 41.31 ± 0.62 | 4.04 ± 0.57 | 176.69 ± 14.77 | 70.82 ± 1.19 | 245.44 ± 3.58 | 8.49 ± 0.08 |
Medium-dose BBE | 41.58 ± 0.45 | 3.33 ± 0.22 | 158.99 ± 10.16 | 60.01 ± 1.23 | 253.22 ± 7.68 | 7.28 ± 0.16 |
High-dose BBE | 41.69 ± 0.56 | 3.10 ± 1.27 | 151.37 ± 3.76 | 53.94 ± 4.97 | 266.19 ± 2.55 | 7.12 ± 0.21 |
Targets | Binding Free Energy (kcal/mol) | Numbers of Bonds |
---|---|---|
PXR | −8.7 | 10 |
Cyt P450 1B1 | −8.2 | 14 |
Bcl-2 | −7.3 | 6 |
Caspase 9 | −7.2 | 5 |
Cytochrome c | −7.6 | 4 |
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Xiao, T.; Guo, Z.; Fu, M.; Huang, J.; Wang, X.; Zhao, Y.; Tao, L.; Shen, X. Amelioration of Alcoholic Liver Disease by Activating PXR-Cytochrome P450s Axis with Blackberry Extract. Separations 2022, 9, 321. https://doi.org/10.3390/separations9100321
Xiao T, Guo Z, Fu M, Huang J, Wang X, Zhao Y, Tao L, Shen X. Amelioration of Alcoholic Liver Disease by Activating PXR-Cytochrome P450s Axis with Blackberry Extract. Separations. 2022; 9(10):321. https://doi.org/10.3390/separations9100321
Chicago/Turabian StyleXiao, Ting, Zhenghong Guo, Min Fu, Jiaoyan Huang, Xiaowei Wang, Yuqing Zhao, Ling Tao, and Xiangchun Shen. 2022. "Amelioration of Alcoholic Liver Disease by Activating PXR-Cytochrome P450s Axis with Blackberry Extract" Separations 9, no. 10: 321. https://doi.org/10.3390/separations9100321