Berberine Is a Promising Alkaloid to Attenuate Iron Toxicity Efficiently in Iron-Overloaded Mice

Abstract

Iron toxicity in iron-overloaded conditions, including high iron diet and blood transfusion, causes deleterious effects on vital organs. There currently are a number of chemical chelators in clinics to reduce iron concentration, for example , deferoxamine and deferiprone, but these produce diverse side effects. Hence, the need for a safe and effective iron chelator is demanded. To evaluate rigorously the potential of berberine on iron chelation and its anti-oxidant effect, 30 mice were divided into 5 groups of 6. Except for the control group, other groups received iron sucrose 5 times a week for 4 successive weeks as an i.p injection. Afterward, either berberine or deferoxamine was injected for 1 month. The mice were then euthanized and liver, kidney and lungs were carefully removed for biochemical and pathological analysis. In comparison with the iron group with an extraordinary amount of iron deposits, berberine (20 mg/kg/day) dramatically reduced iron sedimentation in all tissues ( P < 0.01). Moreover, berberine lowered clinical symptoms of iron overdose, including inflammation, fibrosis and tissue degeneration. In terms of the activity of antioxidant enzymes, catalase and superoxide dismutase, iron overdose greatly reduced their activity compared to the control group. Berberine progressively increased their activity in comparison with the controls by lowering oxidative conditions ( P < 0.05). Iron overdose similarly increased lipid peroxidation by increasing the level of malondialdehyde. Berberine promptly suppressed lipid peroxidation in an efficient manner and reduced the level of malondialdehyde, a marker of lipid peroxidation in the tissues. Accordingly, berberine, as a natural antioxidant compound, could adequately serve as a substitute for chemical chelators with fewer side effects and comparable effectiveness.

The natural iron chelators' ferulic acid and caffeic acid rescue mice's brains from side effects of iron overload

“…FA and CaA increased CAT activity in the brain, liver, and serum of the treatment mice (Figures 6A-C). Previous studies have shown that the antioxidant enzyme activity was affected by iron overload; and natural products and DFO increased the antioxidant enzyme activity (2,40,41).…”

“…Due to the negative effects of DFO, the use of natural compounds as iron chelators is justified. Other studies have shown some natural products, such as CaA, FA, Berberine, and Vanillic acid, reduced iron content in the heart or liver significantly (2,(40)(41)(42). Resveratrol reduces oxidative stress in the brains of treated rats (43).…”

A Review of Fibraurea tinctoria and Its Component, Berberine, as an Antidiabetic and Antioxidant

“…An in vivo study on iron-overloaded mice by Aalikhani et al showed that berberine decreased total iron levels in the liver, kidney, and lung tissues. Berberine prevents lipid peroxidation by reducing excess iron and chelating it in tissues, which is equivalent to DFO, an iron-chelating drug [ 181 ].…”