Oral Asiatic Acid Improves Cognitive Function and Modulates Antioxidant and Mitochondrial Pathways in Female 5xFAD Mice
Abstract
:1. Introduction
2. Materials and Methods
2.1. Mouse Experimental Diets
2.2. Animals
2.3. Conditioned Fear Response (CFR) Test
2.4. Synaptosomal Isolation
2.5. Analysis of Mitochondrial Function
2.6. Gene Expression
2.7. Immunohistochemistry
2.8. Quantification of AA in Plasma Using Liquid–Chromatography Tandem Mass Spectrometry (LC-MS/MS)
2.9. Statistical Analysis
3. Results
3.1. AA Treatment Improves Associative Memory in Female 5xFAD Mice
3.2. AA Treatment Does Not Alter Aβ Plaque Burden
3.3. AA Treatment Attenuates Deficits in Synaptic Gene Expression in Female 5xFAD Mice
3.4. AA Treatment Improves Mitochondrial Bioenergetics in 5xFAD Mice
3.5. AA Increases Expression of ETC Genes in Female 5xFAD Mice
3.6. AA Induces Expression of Antioxidant Genes in Female 5xFAD Mice
3.7. AA Concentration in Plasma
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
AD | Alzheimer’s disease |
Aβ | Beta-amyloid |
OS | Oxidative stress |
ROS | Reactive oxygen species |
ETC | Electron transport chain |
NRF2 | Nuclear factor (erythroid-derived 2)-like2 |
ARE | Antioxidant response element |
CAW | Centella asiatica water extract |
AA | Asiatic acid |
APP | Amyloid precursor protein |
PS1 | Human presenilin 1 |
FAD | Familial Alzheimer’s disease |
CFR | Conditioned Fear Response |
PSD95 | Post-synaptic density protein 95 |
GCLC | Glutamate-cysteine ligase catalytic subunit |
HMOX1 | Heme oxygenase 1 |
Mt-ND1 | Mitochondrially encoded NADH:Ubiquinone Oxidoreductase Core Subunit 1 |
Mt-CYB | Mitochondrially Encoded Cytochrome B |
Mt-CO1 | Mitochondrially Encoded Cytochrome C Oxidase I |
Mt-ATP6 | Mitochondrially Encoded ATP Synthase Membrane Subunit 6 |
GAPDH | Glyceraldehyde-3phosphate dehydrogenase |
QPCR | Quantitative PCR |
LC-MS/MS | Liquid–chromatography tandem mass spectrometry |
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Plasma (ng/mL +/− SEM) | ||
---|---|---|
Females | WT | 704.8 +/− 521.6 |
5xFAD | 1125.4 +/− 849.1 | |
Males | WT | 464.1 +/− 317.2 |
5xFAD | 406.7 +/− 341.5 |
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Varada, S.; Chamberlin, S.R.; Bui, L.; Brandes, M.S.; Gladen-Kolarsky, N.; Harris, C.J.; Hack, W.; Neff, C.J.; Brumbach, B.H.; Soumyanath, A.; et al. Oral Asiatic Acid Improves Cognitive Function and Modulates Antioxidant and Mitochondrial Pathways in Female 5xFAD Mice. Nutrients 2025, 17, 729. https://doi.org/10.3390/nu17040729
Varada S, Chamberlin SR, Bui L, Brandes MS, Gladen-Kolarsky N, Harris CJ, Hack W, Neff CJ, Brumbach BH, Soumyanath A, et al. Oral Asiatic Acid Improves Cognitive Function and Modulates Antioxidant and Mitochondrial Pathways in Female 5xFAD Mice. Nutrients. 2025; 17(4):729. https://doi.org/10.3390/nu17040729
Chicago/Turabian StyleVarada, Samantha, Stephen R. Chamberlin, Lillie Bui, Mikah S. Brandes, Noah Gladen-Kolarsky, Christopher J. Harris, Wyatt Hack, Cody J. Neff, Barbara H. Brumbach, Amala Soumyanath, and et al. 2025. "Oral Asiatic Acid Improves Cognitive Function and Modulates Antioxidant and Mitochondrial Pathways in Female 5xFAD Mice" Nutrients 17, no. 4: 729. https://doi.org/10.3390/nu17040729
APA StyleVarada, S., Chamberlin, S. R., Bui, L., Brandes, M. S., Gladen-Kolarsky, N., Harris, C. J., Hack, W., Neff, C. J., Brumbach, B. H., Soumyanath, A., Quinn, J. F., & Gray, N. E. (2025). Oral Asiatic Acid Improves Cognitive Function and Modulates Antioxidant and Mitochondrial Pathways in Female 5xFAD Mice. Nutrients, 17(4), 729. https://doi.org/10.3390/nu17040729