Are Mangiferin and Mangiferin-Containing Plant Extracts Helpful for Iron-Loaded Transfusion-Dependent and Non-Transfusion-Dependent Thalassaemia Patients?

Ari Estuningtyas,Purnama Fajri,Pustika Amalia Wahidiyat,Klaus Zwicker,Hans-Joachim Freisleben,Tri Wahyuni,Seruni K.U Freisleben

doi:10.13005/bpj/1345

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.

Highlights

In Indonesia, the frequency of b-thalassaemia gene and HbE carriers ranges up to 33%, representing the most frequent single genetic disorder[1]
Whereas in transfusion-dependent thalassaemia (TDT), regular blood transfusions must be accompanied by iron chelation therapy, this has not been clear in the same way for nontransfusion-dependent thalassaemia (NTDT) patients
Body weight of the rats In the beginning of the study, mean weight of the rats was 200 g and 250 g by the end of the study, i.e., all groups gained about 50 g BW, except for the iron overloaded group (IO) without any further treatment, which slightly lost BW

Summary

INTRODUCTION

In Indonesia, the frequency of b-thalassaemia gene and HbE carriers ranges up to 33%, representing the most frequent single genetic disorder[1]. We investigate mangiferin and a mangiferin-containing leaf extract whether they are suitable for already iron-loaded experimental animals (resembling TDT) and in states of the developing iron overload which may be rather preventive and resembling NTDT syndromes. Another aspect is investigated in our study, i.e., the antioxidant capacity of mangiferin in addition to the iron-chelating activity, which can have an antioxidant effect by itself, because in some chelate complexes iron is not active in generating free radicals. We confirmed the superoxide anion radical-scavenging activity of both mangiferin and the mangiferin-iron complex in an in-vitro system by electron paramagnetic resonance (EPR) spectroscopy[22,23]

MATERIALS AND METHODS

RESULTS

DISCUSSION

CONCLUSION