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Evaluation of Insulin Resistance Induced Brain Tissue Dysfunction in Obese Dams and their Neonates: Role of Ipriflavone Amelioration


Rania A. Gad, Eman S. Abdel-Reheim, Gaber M.G. Shehab, Hani S. Hafez and Abdelaziz S.A. Abuelsaad*   Pages 1 - 14 ( 14 )


Background: Nonalcoholic steatohepatitis (NASH) is associated with activation of liver fibrogenesis and predisposes to cirrhosis and associated morbi-mortality. A high fat high cholesterol diet (HFD) was provided to female albino rats to establish a NASH model. It is well known that the offspring of obese mothers have an increased risk of obesity and diabetes. The present study aimed at evaluating the ameliorative effects of ipriflavone (IP) as a natural food supplement on the lipid metabolism, improving insulin sensitivity, reducing oxidative stress and inflammation, modifying metabolic risk factors and/or reduce brain damage, in both neonates and their dams.

Materials and Methods: The present aim was achieved by evaluating the oxidative stress and antioxidant defense system biomarkers, as thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH), catalase, and superoxide dismutase (SOD) activities. In addition, neurotransmitter acetylcholine (Ach) and acetylcholine esterase (AchE) activities, as well as levels of the apolipoprotein E4 (APOE4); β-secretase, hyper phosphor-tau and β-amyloid 42; 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMG CoA R)” and COX-II by immunoblotting assays in the brain tissue of neonates and theirs dams in all the studied groups.

Results: A very significant amelioration in acetylcholine and acetylcholine esterase neurotransmitters, Alzheimer’s makers (β-amyloid), antioxidants (reduced glutathione (GSH) contents, catalase (CAT) and superoxide dismutase (SOD); and inflammatory cytokines in NASH model is observed upon administrating ipriflavone (IP) as a natural food supplement. The multifunctional activities of ipriflavone as an antioxidant, anti-inflammatory and anti-insulin resistance drug were discussed and correlated with other investigations.

Conclusion: Regarding steatohepatitis, the present study confirmed the anti-inflammatory effects of the ipriflavone (IP). Therefore, future studies should focus on hepatic fatty acid uptake, hepatic lipogenesis, and fatty acid oxidation and the role of IP in regulating hepatic fat metabolism. In addition, natural products like IP could be combined with the highly used pharmaceutical drugs to reduce the side effects of nonalcoholic steatohepatitis, and minimize progression of dementia. Moreover, present study supports further attempts to heal the neural dysfunction via antioxidant and anti-inflammatory cascade activities using ipriflavone (IP).


Neonates - Obesity - insulin resistance - Nonalcoholic fatty liver disease (NAFLD)”- Ipriflavone - HMG CoA R- Acetylcholine esterase - β_Secretase – APOE4- Oxidative stress.


Department of Pharmacology, Faculty of Pharmacy, NAHDA University Beni-Suef (NUB), Beni-Suef 62511, Physiology Immunology Divisions; Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef 62511, Department of Biochemistry, College of Medicine, Taif University, Taif 21944, Zoology Department, Faculty of Science, Suez University, Suez, Physiology Immunology Divisions; Department of Zoology, Faculty of Science, Beni-Suef University, Beni-Suef 62511

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