Identifying Key Genes of Proanthocyanidin Intervention in Fluoride-Induced Liver Injury: Integrated Molecular Docking and Experimental Validation
Abstract
1. Introduction
2. Materials and Methods
2.1. Animal Rearing and Treatment
2.2. Main Reagents and Instruments
2.3. Determination of Serum ALT and AST
2.4. Western Blot
2.5. Statistical Analysis
2.6. Prediction of Potential Targets of PC
2.7. Prediction of Potential Targets for Fluoride-Induced Liver Injury
2.8. Construction of PPI Network and Screening of Key Targets
2.9. GO and KEGG Enrichment Analysis
2.10. Construction of the miRNA Regulatory Network for Key Targets
2.11. Molecular Docking
3. Results
3.1. Prediction of Potential Targets for PC and Fluoride-Induced Liver Injury
3.2. Common Targets of Proanthocyanidins and Fluoride-Induced Liver Injury
3.3. Construction of PPI Network and Screening of Key Targets
3.4. GO and KEGG Pathway Enrichment Analysis
3.5. Construction of Genes-miRNA Network for Key Targets
3.6. The Results of Molecular Docking
3.7. Histological Evidence of GSPE Alleviating Liver Injury in Rats Caused by Fluoride Poisoning
3.8. The Effects of NaF and GSPE on the Expression of ALT and AST in the Liver
3.9. The Effects of NaF and GSPE on the Expression of the mTOR/P70s6k Signaling Pathway in the Liver
3.10. The Effects of NaF and GSPE on the Expression of Autophagy-Related Proteins in the Liver
3.11. The Effects of NaF and GSPE on the Expression of Apoptosis-Related Proteins in the Liver
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
NaF | Sodium fluoride |
PC | Proanthocyanidin |
GSPE | Grape seed proanthocyanidin extract |
AST | Aspartate aminotransferase |
ALT | Alanine aminotransferase |
GO | Gene ontology |
KEGG | Kyoto encyclopedia of genes and genome |
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Protein Ligand | Vina Score (kcal/mol) | Cavity Volume (Å3) |
---|---|---|
TP53 | −7.0 | 78 |
IL1B | −8.2 | 185 |
CASP3 | −8.7 | 1412 |
IL6 | −9.0 | 134 |
ALB | −9.5 | 1986 |
BCL2 | −7.4 | 285 |
PARP1 | −10.9 | 2969 |
mTOR | −9.8 | 7094 |
Group | AST (U/L) | ALT (U/L) |
---|---|---|
Control | 36.14 ± 0.08 | 25.52 ± 0.24 |
NaF (100 mg/L) | 51.25 ± 6.00 * | 42.42 ± 5.47 * |
GSPE (400 mg/L) | 35.26 ± 1.17 | 27.6 ± 2.47 |
NaF (100 mg/L) + GSPE (100 mg/kg·bw) | 36.98 ± 0.36 # | 25.74 ± 1.25 # |
NaF (100 mg/L) + GSPE (200 mg/kg·bw) | 36.04 ± 0.63 # | 24.71 ± 0.97 # |
NaF (100 mg/L) + GSPE (400 mg/kg·bw) | 34.63 ± 0.78 # | 19.13 ± 1.71 ## |
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Wu, Z.; Xiao, M.; Gong, Z.; Wang, B.; Zhao, W.; Guo, Y.; Yang, L. Identifying Key Genes of Proanthocyanidin Intervention in Fluoride-Induced Liver Injury: Integrated Molecular Docking and Experimental Validation. Genes 2025, 16, 1037. https://doi.org/10.3390/genes16091037
Wu Z, Xiao M, Gong Z, Wang B, Zhao W, Guo Y, Yang L. Identifying Key Genes of Proanthocyanidin Intervention in Fluoride-Induced Liver Injury: Integrated Molecular Docking and Experimental Validation. Genes. 2025; 16(9):1037. https://doi.org/10.3390/genes16091037
Chicago/Turabian StyleWu, Zhiyu, Menghuan Xiao, Zelin Gong, Benjie Wang, Wenxin Zhao, Yiyuan Guo, and Lu Yang. 2025. "Identifying Key Genes of Proanthocyanidin Intervention in Fluoride-Induced Liver Injury: Integrated Molecular Docking and Experimental Validation" Genes 16, no. 9: 1037. https://doi.org/10.3390/genes16091037
APA StyleWu, Z., Xiao, M., Gong, Z., Wang, B., Zhao, W., Guo, Y., & Yang, L. (2025). Identifying Key Genes of Proanthocyanidin Intervention in Fluoride-Induced Liver Injury: Integrated Molecular Docking and Experimental Validation. Genes, 16(9), 1037. https://doi.org/10.3390/genes16091037