Multidimensional Neuroprotective Effects of Combined Ubisol-Q10 and Ashwagandha (Withania somnifera) in Male and Female 5XFAD Mice
4 affiliations
- 1Department of Integrative Biology, University of Windsor, 401 Sunset Avenue, Windsor, ON N9B 3P4, Canada
- 2Department of Chemistry & Biochemistry, University of Windsor, 401 Sunset Avenue, Windsor, ON N9B 3P4, Canada
- 3Department of Biomedical Science, University of Windsor, 401 Sunset Avenue, Windsor, ON N9B 3P4, Canada
- 4Department of Psychology, University of Windsor, 401 Sunset Avenue, Windsor, ON N9B 3P4, Canada
Abstract
Background/Objectives: Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by interconnected pathological processes including mitochondrial dysfunction, oxidative stress, impaired autophagic processes, neuroinflammation, neuronal degeneration, and progressive functional decline. Natural health products (NHPs), coenzyme-Q10 (CoQ10) and Ashwagandha (Withania somnifera) (ASH), have been previously reported to possess antioxidant, anti-inflammatory, mitochondrial-supportive, neuroprotective, and neurotrophic properties. This work investigates the neuroprotective effects of a bioavailability-enhanced formulation, Ubisol-Q10 (UQ), and ethanolic ASH extract, combined as a “Tonic,” across multiple domains of AD pathology. Methods: The effects of long-term administration were evaluated in male and female 5XFAD mice from 2.5 to 11 months of age. Longitudinal magnetic resonance imaging assessed hippocampal and white matter volumes, a frailty index assessed physiological resilience, Novel Object and Novel Location Recognition testing assessed spatial and non-spatial memory, while post-mortem Nissl, Golgi–Cox, and immunofluorescence evaluated cellular density, dendritic morphology, amyloid pathology, neuroinflammation, autophagy-associated signaling, and astrocytic activity. Results: Across these measures, Tonic treatment preserved brain volumes, reduced amyloid pathology and inflammation, and modulated autophagy-associated pathways. Treatment also preserved dendritic architecture, frailty progression, and novelty-recognition behavior. Females demonstrated particularly pronounced preservation of white matter structure and increased dendritic density, whereas males showed strong modulation of inflammatory and autophagy-associated markers. Astrocytic immunoreactivity also demonstrated sex- and region-specific patterns, suggesting that glial responses may contribute differently to structural preservation in males and females. Conclusions: Together, these findings support that UQ + ASH may provide diverse protection against AD neurodegeneration. The observed sex-specific responses emphasize the importance of incorporating sex into preclinical evaluation of novel interventions for neurodegenerative diseases.
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BibTeX
@article{dube2026multidimensional,
title = {{Multidimensional Neuroprotective Effects of Combined Ubisol-Q10 and Ashwagandha (Withania somnifera) in Male and Female 5XFAD Mice}},
author = {Keanna Dube and Alex Stoinescu and Julia Sadler and Michelle Truong and Natasha Malakoti-Negad and Maira Chaudhry and Rohan Talukdar and Jerome Cohen and Siyaram Pandey},
journal = {Nutrients},
year = {2026},
month = oct,
doi = {10.3390/nu18193270},
url = {https://europepmc.org/article/PMC/PMC13667026},
note = {CC BY},
}
RIS
TY - JOUR
TI - Multidimensional Neuroprotective Effects of Combined Ubisol-Q10 and Ashwagandha (Withania somnifera) in Male and Female 5XFAD Mice
AU - Keanna Dube
AU - Alex Stoinescu
AU - Julia Sadler
AU - Michelle Truong
AU - Natasha Malakoti-Negad
AU - Maira Chaudhry
AU - Rohan Talukdar
AU - Jerome Cohen
AU - Siyaram Pandey
PY - 2026
DA - 2026/10/01
JO - Nutrients
DO - 10.3390/nu18193270
UR - https://europepmc.org/article/PMC/PMC13667026
AB - Background/Objectives: Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by interconnected pathological processes including mitochondrial dysfunction, oxidative stress, impaired autophagic processes, neuroinflammation, neuronal degeneration, and progressive functional decline. Natural health products (NHPs), coenzyme-Q10 (CoQ10) and Ashwagandha (Withania somnifera) (ASH), have been previously reported to possess antioxidant, anti-inflammatory, mitochondrial-supportive, neuroprotective, and neurotrophic properties. This work investigates the neuroprotective effects of a bioavailability-enhanced formulation, Ubisol-Q10 (UQ), and ethanolic ASH extract, combined as a “Tonic,” across multiple domains of AD pathology. Methods: The effects of long-term administration were evaluated in male and female 5XFAD mice from 2.5 to 11 months of age. Longitudinal magnetic resonance imaging assessed hippocampal and white matter volumes, a frailty index assessed physiological resilience, Novel Object and Novel Location Recognition testing assessed spatial and non-spatial memory, while post-mortem Nissl, Golgi–Cox, and immunofluorescence evaluated cellular density, dendritic morphology, amyloid pathology, neuroinflammation, autophagy-associated signaling, and astrocytic activity. Results: Across these measures, Tonic treatment preserved brain volumes, reduced amyloid pathology and inflammation, and modulated autophagy-associated pathways. Treatment also preserved dendritic architecture, frailty progression, and novelty-recognition behavior. Females demonstrated particularly pronounced preservation of white matter structure and increased dendritic density, whereas males showed strong modulation of inflammatory and autophagy-associated markers. Astrocytic immunoreactivity also demonstrated sex- and region-specific patterns, suggesting that glial responses may contribute differently to structural preservation in males and females. Conclusions: Together, these findings support that UQ + ASH may provide diverse protection against AD neurodegeneration. The observed sex-specific responses emphasize the importance of incorporating sex into preclinical evaluation of novel interventions for neurodegenerative diseases.
SN - 2072-6643
ER -