ObjectiveIron accumulation in the brain leads to the development of Alzheimer’s and Parkinson’s diseases. Nowadays, iron chelation therapy is the best way to decrease the side effects of iron and amyloid plaques accumulation. Iron chelators are commonly used for the treatment of Alzheimer’s disease. Previous studies have shown that natural products such as phenol and flavonoid compounds could chelate heavy metals. In the current study, we examined the iron chelation activity of hesperidin and coumarin on the brain tissue of iron-overloaded mice.Methods48 NMRI male mice were divided into eight groups (n = 6). Six groups were treated with iron dextran (100 mg/kg/day) four times a week for 6 weeks. After stopping the injections for a month, five groups of iron-overloaded mice were treated with hesperidin, coumarin, and desferal four times a week subsequent for four subsequent weeks. Finally, the mice were anesthetized, and blood samples were collected from the ventricle of the heart for subsequent examination. The brain tissues were isolated and fixed in the 4% paraformaldehyde solution for Perl’s staining.ResultsThe results show that hesperidin and coumarin could strongly chelate excessive iron from the serum and deposit iron from the brain tissue compared to desferal group. Catalase and super oxidase activity were decreased in the iron-overloaded group, but in the treated group by hesperidin and coumarin, the enzyme’s activity was increased significantly.ConclusionHesperidin and coumarin, as natural products, are powerful options to chelate iron ions and increase the activity of antioxidant enzymes.

Studies have shown that iron accumulation in the brain leads to neurogenic disorders. Novel iron chelating agents such as natural remedies are useful to decrease the side effects of iron in the brain. In addition, flavones and polyphenols are capable of chelating metals. In the current study, we evaluated the iron chelating capacity of ferulic acid and caffeic acid in the brain tissues of iron-overloaded mice. The mice received iron dextran intraperitoneally four times a week for 6 weeks. Next, blood samples were taken from the mice. In addition, brain tissues were excised for tissue staining as well as total iron and catalase (CAT) activity assessment. Ferulic acid and caffeic acid significantly decreased iron content in both brain and serum samples. Ferulic acid decreased iron by 50 and 51% more than the iron dextran-treated mice and by 43 and 2% more than desferal (DFO)-treated mice in serum and brain, respectively. In addition, caffeic acid reduced iron 57% more than the iron-treated group and 49 and 2% more than the desferal-treated group in the serum and brain, respectively. The catalase activity decreased with the increase in iron. By administering natural compounds, the catalase activity was increased equal to that of the control group. Thus, ferulic acid and caffeic acid might be possible natural iron chelators for brain iron overload therapy.

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