Mangiferin and mangiferin-containing leaf extract from Mangifera foetida L for therapeutic attenuation of experimentally induced iron overload in a rat model

Ari Estuningtyas,Hans-Joachim Freisleben,Ernie H Poerwaningsih,Tri Wahyuni,Pustika Amalia Wahidiyat

doi:10.15171/jhp.2019.04

Abstract

Introduction: Thalassemia is a hereditary anemia usually treated with regular blood transfusions, which can result in elevated levels of total iron in the body. As soon as the capacity of iron-regulating proteins (e.g., ferritin, transferrin) are used up, free plasma iron increases generating reactive oxygen species (ROS), leading to oxidative stress. Hence, blood transfusions should be accompanied by iron-chelating therapy, e.g., deferiprone (DFP). The purpose of this study was to evaluate the effect of mangiferin (M) and an aqueous leaf extract of Mangifera foetida L (EMF) as alternative iron-chelating antioxidants in an animal model. Methods: Thirty male Sprague Dawley rats were randomly divided into 5 equal groups: normal control, iron overload (IO), IO+DFP, IO+M, and IO+EMF. Iron overload was induced by intraperitoneal iron dextran injection with a total dose of 90 mg/mouse (15 mg Fe/mouse every 3-4 days for 3 weeks) followed by oral administration of DFP 462.5 mg/kg, mangiferin 75 mg/kg, or EMF 2.930 g/kg for 7 days. Results: Body weight (BW) increased in all groups during the 4 weeks of experiment, except for the IO group. As expected, DFP decreased significantly the total plasma iron and increased iron excretion via urine in iron-overloaded rats (positive control), mangiferin and EMF had similar – although slightly smaller – effects than DFP. The antioxidant activity of M and EMF were stronger compared to DFP as determined by plasma superoxide dismutase (SOD) activity. Conclusion: Mangiferin and EMF have iron-chelating and antioxidant effects and might be used for the treatment of iron overload in the body.

Highlights

Thalassemia is a hereditary anemia usually treated with regular blood transfusions, which can result in elevated levels of total iron in the body
In normal controls the difference in iron concentration was +1.22±0.57 μg/mL, in the iron overload (IO) group the difference in iron concentration was -15.0814.78 μg/mL, whereas the decrease was significant in all therapy groups: 261.92±183.20 μg Fe/mL in IO+DFP, 217.08±198.79 μg Fe/mL in IO+M, and 168.20±166.24 μg Fe/mL in IO+extract of Mangifera foetida L (EMF)
In the IO group, iron excretion increased by 2.83±1.64 μg/ mL, in the IO+DFP group, iron excretion increased by 39.27±6.71 μg/mL, in the IO+M group by 12.30±5.48 μg/ mL, and in the IO+EMF group by 3.99±1.93 μg/mL

Summary

Introduction

Thalassemia is a hereditary anemia usually treated with regular blood transfusions, which can result in elevated levels of total iron in the body. Iron overload was induced by intraperitoneal iron dextran injection with a total dose of 90 mg/mouse (15 mg Fe/mouse every 3-4 days for 3 weeks) followed by oral administration of DFP 462.5 mg/kg, mangiferin 75 mg/kg, or EMF 2.930 g/kg for 7 days. DFP decreased significantly the total plasma iron and increased iron excretion via urine in iron-overloaded rats (positive control), mangiferin and EMF had similar – slightly smaller – effects than DFP. Conclusion: Mangiferin and EMF have iron-chelating and antioxidant effects and might be used for the treatment of iron overload in the body. The goal of treatment of iron overload due to repeated transfusions in patients with thalassemia can often not be reached because of price constraints

Objectives

Methods

Results

Discussion

Conclusion