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Investigating the protective and therapeutic potential of new generation antioxidant combinations in the brain: an
Büşra Dönmez1, Elif Naz Gürsoy2, Kanuni Barbaros Balabanli2
1Department of Neurology, Ankara Bilkent City Hospital, Ankara, Turkey.
Abstract:
The increasing elderly population has brought healthy aging into focus. Aging is a multifactorial process characterized by the progressive decline of cellular and tissue functions, largely due to cumulative oxidative stress. Antioxidant-based strategies have therefore gained prominence as potential interventions. This study investigated the protective and therapeutic effects of Squalene (SQ) and Saponin (SP), individually and in combination, on aging-related biomarkers in brain tissue using a D-Galactose (D-Gal)-induced rat model. Forty-eight male Sprague-Dawley rats (200-250 g) were randomly divided into eight groups (n = 6). Aging was induced in four groups via intraperitoneal administration of D-Gal (300 mg/kg/day) for six weeks. One group received no antioxidants, while others were treated orally with SQ (2.66 mL/kg/day), SP (100 mg/kg/day), or their combination. Non-aging groups received the same antioxidant treatments without D-Gal. At the end of the intervention, brain tissues were collected for biochemical analysis. Spectrophotometric assessments included Malondialdehyde (MDA), Glutathione (GSH), Nitric oxide derivatives (NOx), Ascorbic acid (AA), and Protein carbonyls (PC). Forkhead Box O3A (FOXO3A), Nuclear factor erythroid 2-related factor 2 (NRF2), Sirtuin 1 (SIRT1), Paraoxonase 1 (PON1), and Klotho were quantified by ELISA. Combined SQ and SP treatment significantly decreased oxidative stress markers (MDA, NOx, PC) and increased antioxidant defenses (GSH, AA) as well as aging-related molecules (FOXO3A, NRF2, SIRT1, PON1, Klotho) (p < 0.05). Serum Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) levels were also reduced. These findings demonstrate, for the first time, that combined SQ and SP administration can mitigate aging-related oxidative stress and molecular alterations in brain tissue.
Insights
Combined Squalene (SQ) and Saponin (SP) effectively combat aging-related oxidative stress in brain tissue. This antioxidant combination improved key aging biomarkers and reduced harmful oxidative markers in a D-Galactose induced rat model.
Area of Science:
- Gerontology and Neuroscience
- Biochemistry and Pharmacology
Background:
- Aging is a complex process marked by declining cellular function, often exacerbated by oxidative stress.
- Antioxidant interventions are explored for their potential to mitigate aging effects.
- Healthy aging research is crucial due to the growing elderly population.
Purpose of the Study:
- To evaluate the protective and therapeutic effects of Squalene (SQ) and Saponin (SP) on aging biomarkers in brain tissue.
- To investigate the impact of individual and combined SQ and SP treatments in a D-Galactose induced aging rat model.
- To assess changes in oxidative stress markers and key aging-related molecules.
Main Methods:
- A D-Galactose induced rat model was used to simulate aging.
- Rats were divided into groups receiving no treatment, D-Galactose, or D-Galactose with SQ, SP, or combined SQ and SP.
- Brain tissues were analyzed for Malondialdehyde (MDA), Glutathione (GSH), Nitric oxide derivatives (NOx), Ascorbic acid (AA), and Protein carbonyls (PC).
- Levels of FOXO3A, NRF2, SIRT1, PON1, and Klotho were quantified using ELISA.
Main Results:
- Combined SQ and SP treatment significantly reduced oxidative stress markers (MDA, NOx, PC).
- Antioxidant defenses (GSH, AA) were significantly increased by combined SQ and SP.
- Key aging-related molecules (FOXO3A, NRF2, SIRT1, PON1, Klotho) were upregulated with combined treatment.
- Serum ALT and AST levels were reduced, indicating potential liver protection.
Conclusions:
- Combined Squalene and Saponin administration demonstrates significant efficacy in mitigating D-Galactose induced oxidative stress and molecular aging in rat brain tissue.
- This study provides novel evidence for the synergistic benefits of SQ and SP in promoting healthy aging at a molecular level.
- The findings suggest SQ and SP as promising therapeutic agents for age-related neuroprotection.
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