Iron-overload disorder (hemochromatosis) is one of the major reasons of morbidity, caused by genetic disorder of protein involved in regulation of iron absorption or due to multiple transfusion of iron in chronic anemia for example thalassemia. Resulting in initiation and propagation reactive oxygen species which attacking macromolecules of cells such as proteins, lipids, RNA and DNA and ultimately cells death. Leading to a state of oxidative stress associated with many of health problems such as heart failure, liver cirrhosis, fibrosis, gallbladder disorders, diabetes, arthritis, infertility, and cancer. The available chelators drugs can forming soluble, stable complexes with excessive iron andexcreted it in the feces and/or urine. But due to, their high cost, severe side effects, poor oralbioavailability or short plasma half-life make them suboptimal.
Sixteen plant leaves were collected, authenticated and subjected to exhausted extraction by 70% methanol. The obtained leaves extracts were screened for their iron chelation activity using 2,2`- bipyridyl assay. Among the screened extracts, the Mangiferaindica leaves showed the highest iron chelation activity(69.71 ± 0.27%)comparable to positive control, EDTA(70.30 ± 0.08%).
The total extract of theM. indica leaves was partitioned with different solvents (petroleum ether, methylene chloride, ethyl acetate and n-butanol). The resultingfractions were screened for their iron chelation activity using 2, 2`- bipyridyl assay.EtOAcfractionhad the significant chelating activity (123 ± 2.75%),more potent than EDTA(64.12 ± 1.48%) and total extract of M. indica leaves (69.71 ± 0.27%).
The mangiferin compound was subjected to comparison with desferal® to assurance the quality of its chelating activity throughdetermine the active sites responsible of its chelating property and evaluation the effect of its iron-stable complex on its antioxidant activity.
According to introduced results, through different biological analysis. We found that, the iron-overloaded rats treated with ethyl acetate fraction had significant decreases in iron accumulation within liver and spleen (the major organs affected by iron overload). We assume that, the mangiferin may protect from reactive oxygenspecies-stimulatedseveral of disordersby its iron chelatingactivity which promotes its antioxidant property.
Table of Contents
I. Introduction
1. Iron disorders in the human body
Metabolism of Iron
Iron blood disorders
Classification and causes of iron overload
Complications of iron overload
Iron overloads medications
2. Natural compounds as alternative chelating agents
3. Agricultural wastes with reported iron chelating activity
4. Chemical and biological activity of Mangifera Indica L. leaves.
5. Iron Chelation assays
Determination of iron chelation activity by 2-2` bipyridyl reagent
Materials
Methods
II. Phytochemical screening and iron chelating activity
of Mangifera indica L. leaves
III. Bio-guided fractionation of iron chelators from Mangifera indica L. leaves
Identification of the isolated compounds
IV. A comparative study of the iron chelating property
of mangiferin Vs. desferal®
V. In-vivo investigation of the total extract (TM) and the ethyl acetate fraction (EM) of Mangifera indica L. leaves in iron overloaded rats
Isolation, characterization, and biological evaluation of iron chelators from some natural sources
Conclusion
References
Research Objectives and Themes
This work aims to explore agricultural residues as potential, cost-effective sources of natural iron chelators to mitigate complications associated with iron overload, such as hemochromatosis, while providing a safer alternative to synthetic drugs. The research evaluates the antioxidant and iron-chelating properties of various plant leaf extracts, specifically identifying potent polyphenolic compounds like mangiferin and assessing their therapeutic efficacy in iron-overloaded animal models.
- Screening and identification of iron-chelating activity in diverse agricultural wastes.
- Bio-guided fractionation and structural characterization of active phytochemicals.
- Comparative performance analysis of isolated natural compounds against commercial iron-chelating drugs.
- In-vivo assessment of the protective effects of mango leaf extracts against iron-induced oxidative damage in rats.
Excerpt from the Book
I. Introduction
Iron is an important trace element in the human body (Sarkar et al., 2012). It is essential for oxygen and electrons transport within cells and as an integrated part of several enzyme systems (Gupta, 2014). Iron overload (hemochromatosis) maybe caused by genetic disorder of protein involved in regulation of iron absorption or due to multiple transfusion of iron as in chronic anemia (Queiroz-Andrade et al., 2009). Accumulation of iron in the body results in initiation and propagation of reactive oxygen species, which start to attack the cell vital macromolecules such as proteins, lipids, RNA and DNA causing cell damage, DNA mutation and ultimately cell death. This produced state of oxidative stress is associated with many health problems such as heart failure, liver cirrhosis, fibrosis, gallbladder disorders, diabetes, arthritis, infertility, and cancer (Gupta, 2014).
Iron chelators can remove the accumulated iron from the body before causing irreversible tissue damage by forming soluble, stable complexes that can be excreted in the feces and/or urine. Although available iron chelators can reduce iron-related complications, their severe side effects, poor oral bioavailability or short plasma half-life as well as their expensive cost make them suboptimal such as deferoxamine (Desferal®), deferasirox (Exjade®) and deferiprone (Ferriprox®) (Ebrahimzadeh et al., 2008).
The unmet need for iron chelators, could be satisfied by natural products, providing the advantage of being less toxic, wider in safety margin and more economic. The main interest of our study is agricultural residues, being a potential source for biologically active compounds (Duarte and Rai, 2015, Schmidl et al., 2008) with economic and environmental merits(Jain et al., 2014, Zhang et al., 2011).
Mangifera indica L. is a tropical fruit, belonging to family Anacardiaceae. It is widely spread in India, Central America, Asia, and Africa (Lauricella et al., 2017). The Egyptian Agriculture and Land Reclamation provided a statistical study indicates that, the total production of mango is 0.596 million tons in Egypt and about 151,000 Fadden are dedicated to mango trees (Mansour et al., 2008).
Summary of Chapters
I. Introduction: This chapter provides an overview of iron metabolism, the clinical significance of iron overload disorders, and the rationale for investigating natural products as sustainable iron chelators.
II. Phytochemical screening and iron chelating activity of Mangifera indica L. leaves: This section details the systematic extraction and fractionation of mango leaves to identify the most potent fraction for iron-chelating activity.
III. Bio-guided fractionation of iron chelators from Mangifera indica L. leaves: This chapter focuses on the isolation and structural characterization of specific active compounds, namely mangiferin and iriflophenone-3-C-β-D-glucoside.
IV. A comparative study of the iron chelating property of mangiferin Vs. desferal®: The investigation evaluates the chemical and chelating performance of isolated mangiferin against the standard clinical drug desferal®.
V. In-vivo investigation of the total extract (TM) and the ethyl acetate fraction (EM) of Mangifera indica L. leaves in iron overloaded rats: The final chapter presents the physiological evaluation of the extracts' efficacy in mitigating iron accumulation and oxidative stress within an iron-overloaded rat model.
Keywords
Iron overload, Iron chelators, Mangifera indica, Mangiferin, Agricultural wastes, Oxidative stress, Phytochemical screening, Bio-guided fractionation, Antioxidant activity, Desferal, In-vivo study, Polyphenolic compounds, Chelation therapy, Hemochromatosis, Iron metabolism
Frequently Asked Questions
What is the fundamental purpose of this research?
The research aims to identify and evaluate natural iron chelators derived from agricultural waste, specifically mango leaves, to provide a cost-effective and safer alternative to existing synthetic iron-overload treatments.
What are the central topics discussed in the work?
The core topics include iron metabolism, the mechanism of iron overload, the biochemical characterization of polyphenolic compounds, and their potential therapeutic application as antioxidant and iron-chelating agents.
What is the primary research question being addressed?
The study addresses whether extracts from specific agricultural wastes, particularly Mangifera indica leaves, possess sufficient iron-chelating and antioxidant properties to be used as therapeutic alternatives for managing iron overload conditions.
Which scientific methodologies are employed?
The study utilizes a combination of in-vitro assays (bipyridyl and ferrozine assays), phytochemical screening, bio-guided fractionation (using column chromatography), spectroscopic analysis (IR, NMR, Mass Spectrometry), and in-vivo animal testing to validate clinical efficacy.
What does the main body of the work cover?
The main body covers the extraction and screening of plant materials, the isolation of bioactive compounds like mangiferin, comparative chemical analysis with standard drugs, and the evaluation of these compounds' biological effects on iron-overloaded rats.
What defines the character of this research?
This research is defined by its multidisciplinary approach, bridging pharmaceutical chemistry and pharmacology to transform agricultural by-products into high-value bioactive treatments for iron-related medical conditions.
How is the chemical structure of isolated compounds confirmed?
The researchers confirmed the structures through comprehensive spectroscopic techniques, including 1H-NMR, APT, HMBC, and FT-IR, to characterize the xanthoid moiety and glycoside linkages in mangiferin and iriflophenone-3-C-β-D-glucoside.
What significance is attributed to mangiferin?
Mangiferin is identified as the major active polyphenolic constituent in mango leaves, exhibiting potent iron-chelating and antioxidant properties that make it a promising candidate for chelation therapy.
What are the observed in-vivo results?
The in-vivo study showed that treatment with the ethyl acetate fraction of mango leaves significantly decreased iron accumulation in the liver and spleen of iron-overloaded rats, while restoring antioxidant enzyme levels and improving overall liver function.
- Citar trabajo
- Farid Badria (Autor), 2019, Natural Iron Chelator. Chemistry, Biology, and Therapeutic Applications, Múnich, GRIN Verlag, https://www.grin.com/document/509342
