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Updated: May 21, 2025
Behavioral Disturbances: An Innovative Approach to Monitor the Modulatory Effects of a Nutraceutical Diet
Published on: January 3, 2017
Modulating Multiple Molecular Trajectories by Nutraceuticals and/or Physical Activity in
Karema Abu-Elfotuh1,2, Gellan Alaa Mohamed Kamel3,4, Mazin A A Najm5
1Department of Clinical Pharmacy, Faculty of Pharmacy, Al-Azhar University, Cairo, 11884, Egypt.
Insights
This study shows that combining physical activity (PHA) with nutraceuticals like sesamol (SE) and astaxanthin (AST) effectively reduces attention deficit/hyperactivity disorder (ADHD)-like behaviors in rat pups. This combination therapy offers superior neuroprotection against MSG-induced ADHD symptoms compared to individual treatments.
Area of Science:
- Neuroscience
- Pharmacology
- Nutritional Science
Background:
- Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition impacting childhood cognitive and social functions.
- Monosodium glutamate (MSG), a common food additive, has been linked to ADHD-like symptoms in children.
- Nutraceuticals (sesamol, astaxanthin) and physical activity show health benefits, but their neuroprotective role in ADHD is under-investigated.
Purpose of the Study:
- To investigate the impact of sesamol (SE), astaxanthin (AST), and physical activity (PHA), alone and in combination, on ADHD-like behaviors induced by MSG in rat pups.
- To evaluate the neuroprotective effects of these interventions on neurotransmitter levels, biochemical markers, and histopathological changes.
Main Methods:
- Eighty-four male Sprague Dawley rat pups were divided into seven groups: control, MSG, and MSG with PHA, SE, AST, SE+AST, or a combination of PHA+SE+AST.
- Treatments were administered for eight weeks.
- Evaluations included behavioral assessments, neurotransmitter analysis, five pathway biomarkers, histopathology, and immunohistochemistry.
Main Results:
- PHA, SE, and AST, individually or combined, improved attention, locomotor, and cognitive functions in MSG-exposed rats.
- All treatments normalized neurotransmitter levels, biochemical markers, and histological findings.
- The combination of PHA with SE and AST demonstrated superior efficacy across all measured parameters compared to individual treatments.
Conclusions:
- Combining nutraceuticals (SE, AST) with physical activity (PHA) is more effective in ameliorating MSG-induced ADHD-like behaviors in rat pups than standalone treatments.
- These combined interventions modulate key neuroprotective pathways, including HMGB1/RAGE, PI3K/AKT/CREB/BDNF, AMPK/SIRT-1, and PERK/CHOP.
Abstract:
Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition affecting cognitive and social functions all over childhood. Monosodium glutamate (MSG) is a common food additive associated with ADHD-like symptoms in children. Nutraceuticals, like sesamol (SE) and astaxanthin (AST), or physical activity (PHA) were reported to possess beneficial effects on human health. Meanwhile, still their neuroprotective effect against ADHD has been poorly investigated. This study aimed to investigate the impact of SE, AST and PHA either separately or combined on ADHD-like behaviors induced by MSG in rat pups. Eighty-four male Sprague Dawley rat pups were randomly allocated into seven groups; control, MSG, (PHA + MSG), (SE + MSG), (AST + MSG), (SE + AST + MSG), and (COMB [PHA + SE + AST] + MSG) and treated for eight weeks. MSG-induced ADHD-like behavior was evaluated, via assessing behavioral outcomes; neurotransmitters' levels; five pathway biomarkers, coupled with histopathological and immunohistochemical studies. Rats exposed to PHA or treated with SE or AST either separately or combined exhibited enhanced attention, locomotor, and cognitive abilities, compared to MSG-intoxicated group. All treatments remarkably improved MSG-induced abnormalities in neurotransmitters' levels; biochemical markers; along with histological findings, via modulating HMGB1/RAGE/JAK-2/STAT-3, PI3K/AKT/CREB/BDNF, AMPK/SIRT-1 and PERK/CHOP pathways. Nevertheless, the combination of PHA with nutraceuticals (SE and AST) elicited more favorable effects in all measured parameters and histological findings, compared to other treated groups. In conclusion, this study revealed the superiority of the combination of nutraceuticals with PHA, over other standalone treatments, in amelioration of MSG-induced ADHD-like behaviors in rat pups, via fine-tuning of HMGB1/RAGE, PI3K/AKT/CREB/BDNF, AMPK/SIRT-1 and PERK/CHOP pathways.
