Icariin Ameliorates Cyclophosphamide-Induced Renal Encephalopathy by Modulating the NF-κB and Keap1-Nrf2 Signaling Pathways
Abstract
1. Introduction
2. Results
2.1. Molecular Docking Results
2.2. In Vivo Results
2.2.1. ICA Alleviates CTX-Induced Spatial Learning Memory in RE Mice
2.2.2. Serum, Brain, and Kidney Tissue-Related Indicator Tests
2.2.3. H&E, PAS, and Nissl Stain Results
2.2.4. Western Protein Blotting Results for Brain and Kidney Tissues
2.3. In Vitro Results
2.3.1. Effect of ICA on CTX Injury to HT22 and HEK293 Cell Viability
2.3.2. Intracellular ROS Detection
2.3.3. Effect of ICA on CTX-Induced Apoptosis
2.3.4. Detection of Biochemical Indicators
2.3.5. Western Protein Blotting Assay for Apoptosis-Related Proteins Caspase-3, Bax, Bcl-2, and BDNF Expression Levels
3. Discussion
4. Methods and Materials
4.1. Molecular Docking
4.2. Drugs and Reagents
4.3. Instrumentation
4.4. In Vivo Experiments
4.4.1. Grouping and Processing of Animals
4.4.2. Behavioral Tests
- 1.
- Elevated plus maze, EPM
- 2.
- Morris water maze, MWM
- 3.
- Radial arm maze test, RMT
- 4.
- Testing serum and brain and kidney tissue (biochemical indicators)
- 5.
- Histopathological observations
- 6.
- Western blotting
4.5. In Vitro Experiments
4.5.1. Cell Recovery and Culture
4.5.2. Screening for Safe Drug Concentrations
4.5.3. Detection of Cell Viability by CCK-8 Assay
4.5.4. ROS Detection
4.5.5. Hoechst 33342/PI, Annexin V-FITC/PI Staining, and Flow-Through Detection of Apoptosis
4.5.6. Detection of Biochemical Indicators
4.5.7. Cell Western Blotting
4.6. Statistical Analyses
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
ICA | Icariin |
CTX | cyclophosphamide |
ROS | reactive oxygen species |
BDNF | brain-derived neurotrophic factor |
MDA | malondialdehyde |
IL-6 | Interleukin-6 |
NO | nitric oxide |
SOD | superoxide dismutase |
DMEM | Dulbecco’s modified eagle medium |
Cre | creatinine |
UA | uric acid |
BUN | urea nitrogen |
Nissl | Nissant staining |
PAS | periodic acid–Schiff |
HE | hematoxylin–eosin |
FSH | follicle-stimulating hormone |
LH | luteinizing hormone |
T | testosterone |
DA | dopamine |
5-HT | serotonin |
AD | Alzheimer’s disease |
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Group | n | Dose | Error of Working Memory | Reference Memory Error |
---|---|---|---|---|
Control group | 12 | —— | 2.11 ± 0.23 | 3.42 ± 0.11 |
CTX | 12 | 80 mg/kg | 7.56 ± 0.33 ### | 10.44 ± 0.31 ### |
ICA | 12 | 25 mg/kg | 5.04 ± 0.29 ** | 7.11 ± 0.26 *** |
ICA | 12 | 100 mg/kg | 3.48 ± 0.11 *** | 5.11 ± 0.22 *** |
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Shi, M.; Kan, H.; Tang, Y.; Tian, L.; Guo, X.; Chen, W.; Geng, J.; Zong, Y.; Bi, Y.; He, Z. Icariin Ameliorates Cyclophosphamide-Induced Renal Encephalopathy by Modulating the NF-κB and Keap1-Nrf2 Signaling Pathways. Int. J. Mol. Sci. 2025, 26, 4838. https://doi.org/10.3390/ijms26104838
Shi M, Kan H, Tang Y, Tian L, Guo X, Chen W, Geng J, Zong Y, Bi Y, He Z. Icariin Ameliorates Cyclophosphamide-Induced Renal Encephalopathy by Modulating the NF-κB and Keap1-Nrf2 Signaling Pathways. International Journal of Molecular Sciences. 2025; 26(10):4838. https://doi.org/10.3390/ijms26104838
Chicago/Turabian StyleShi, Meiling, Hong Kan, Yijia Tang, Lanshi Tian, Xiangjuan Guo, Weijia Chen, Jianan Geng, Ying Zong, Yunfeng Bi, and Zhongmei He. 2025. "Icariin Ameliorates Cyclophosphamide-Induced Renal Encephalopathy by Modulating the NF-κB and Keap1-Nrf2 Signaling Pathways" International Journal of Molecular Sciences 26, no. 10: 4838. https://doi.org/10.3390/ijms26104838
APA StyleShi, M., Kan, H., Tang, Y., Tian, L., Guo, X., Chen, W., Geng, J., Zong, Y., Bi, Y., & He, Z. (2025). Icariin Ameliorates Cyclophosphamide-Induced Renal Encephalopathy by Modulating the NF-κB and Keap1-Nrf2 Signaling Pathways. International Journal of Molecular Sciences, 26(10), 4838. https://doi.org/10.3390/ijms26104838