Are Mangiferin and Mangiferin-Containing Plant Extracts Helpful for Iron-Loaded Transfusion-Dependent and Non-Transfusion-Dependent Thalassaemia Patients?
Ari Estuningtyas1, Klaus Zwicker2, Tri Wahyuni3, Purnama Fajri3, Pustika Amalia Wahidiyat4, Seruni K.U. Freisleben5 and Hans-Joachim Freisleben6

1Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia.

2Institute of Biochemistry I, Faculty of Medicine, Goethe-University Frankfurt, 60590 Frankfurt, Germany.

3Faculty of Pharmacy, Universitas Indonesia, Jakarta-Depok.

4Department of Paediatrics – Thalassaemia Ward, Dr. Cipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia.

5Department of Physics, Faculty of Mathematics and Natural Sciences, Universitas Indonesia, Jakarta- Depok.

6Medical Research Unit, Faculty of Medicine, Universitas Indonesia, Salemba Raya 6, 10430 Jakarta, Indonesia.

Corresponding Author E-mail: hj.freisleben@t-online.de

Abstract: Treatment of iron overload in thalassaemia is still a great burden for patients, their families and the health care system in developing countries like Indonesia, because of expensiveness and unwanted side effects of chemical iron-chelating therapeutics. This animal study investigates an extract from the leaves of Mangifera foedica L (EMF) and its major active compound, mangiferin, for chelating and antioxidant treatment of iron overload. Sixty rats were randomly divided into 10 groups: control, iron overload (IO), and IO with mangiferin doses between 50 and 200 mg/g BW or 2390 mg of EMF, applied via gastric tubes. For comparison, deferiprone (DFP) was used. Iron overload was induced by intraperitoneal iron dextran resembling two models, transfusion-dependent (TDT) or nontransfusion-dependent thalassaemia (NTDT). Increasing oral doses of mangiferin and EMF did not result in higher mangiferin plasma levels; however, mangiferin administered for four weeks roughly doubled blood levels compared to two weeks. In the TDT model, mangiferin significantly lowered ferritin levels by 21% and plasma iron levels by 60% (EMF by 50%), almost like DFP (by 70%) and increased iron excretion 6-fold via urine (DFP 15-fold, EMF 2-fold). In the NTDT model mangiferin and EMF decreased ferritin levels significantly by about 30%, without significantly decreasing excess plasma iron. Mangiferin increased iron excretion via urine 4-fold (EMF 2-fold) and tended to diminish Fe accumulation in liver and heart. Iron chelating effects of EMF were weaker than of mangiferin, but its in vivo antioxidant activity was stronger. In vitro, both mangiferin and the mangiferin/FeIII complex are potent superoxide radical scavengers, the iron complex being superior.

Keywords: Thalassaemia; Iron Overload; Plasma Ferritin; Iron Excretion; Mangiferin; Electron Paramagnetic Resonance

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