Masterarbeit, 2019
117 Seiten, Note: 4.0
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
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.
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).
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.
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
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.
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.
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.
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.
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.
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.
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.
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.
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.
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