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Natural product-derived therapy for Malaria: Nordihydroguaiaretic acid (NDGA) increases Ferroportin expression, decreases intracellular iron accumulation, inhibits cellular damage, prevents hemolysis, and inhibits malaria infection, via upregulation of its target gene, 21/April/2018, 7.40 am

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Introduction: What they say:

A study from the Section on Human Iron Metabolism, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA shows that “Erythrocytic ferroportin reduces intracellular iron accumulation, hemolysis, and malaria risk.” This study was published, in the 30 March 2018 issue of the journal Science (one of the best journals in science with an impact factor of 37+), by Prof. Rouault, Zhang, and others.


What we say:

On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that:  Natural product-derived therapy for Malaria: Nordihydroguaiaretic acid (NDGA) increases Ferroportin expression, decreases intracellular iron accumulation, inhibits cellular damage, prevents hemolysis, and inhibits malaria infection, via upregulation of its target gene


What is known?

A number of studies suggests that malarial parasite disrupts iron regulation in RBCs of humans and thereby causes anemia. Unfortunately, iron supplementation therapy exacerbates malarial infections, rather than attenuating malarial infections. However, the molecular basis of this anomaly is far from clear.

Prof. Rouault’s research team has recently shown that: (1)iron transporter ferroportin (FPN) is present in abundant amounts in RBCs; (2) iron supplementation decreases ferroportin’s activity; (3) knock-out of ferroportin gene in erythroid cells: (a) increases the levels of intracellular iron; (b) augments cellular damage; (c) accelerates hemolysis; and (d) increases mortality in malaria-infected mice; (5) hepcidin-induced degradation of ferroportin is prevented by mutation (Q248H) in ferroportin  gene and this mutation is common in african population (explaining why considerable no. of people in African populations are resistant to malarial infection). Together, this study suggests that increasing the expression of ferroportin in precursors of RBCs may inhibit accumulation of intracellular iron, decrease oxidative stress, and attenuate malarial infection.


From Significance of the study to Public health relevance:

Given that: (1) 214 million new cases of malaria had been reported in 2015; (2) nearly 438,000 people out of 214 million people who were infected with Malaria had died in 2015; (3) malaria has the potential to affect nearly half the global population; (4) molecular pathways involved and the mechanism of development of drug-resistant malaria are far from understood; (4) treating drug-resistant malaria is still a daunting task; (5) millions of deaths occur due to malaria every year; (6) out of the 125 million international travellers who visit countries, such as Ivory Coast, Angola, Burkina Faso, Burkina Faso, Mozambique and Mali, more than 30, 000 contract the disease; (7) most of the malaria cases are registered in countries, such as sub-Saharan Africa—that cannot afford high-cost required for the treatment of drug-resistant malaria—compared to developed countries, such as US (10,000 malaria cases per year) and UK (1,500 malaria cases/year), (8) humans could not mount immunity against blood stage-malaria; and prevent re-infections; and (9) billions of dollars are being spent each year globally for the treatment of malaria, there is an urgent need to find: (i) a way to inhibit drug-resistant malaria; and (ii) a side-effect-free-Natural product-based drug that prevents relapse/recurrence of blood-stage/drug-resistant Malaria.


From Research Findings to Therapeutic opportunity:

This study suggests a natural compound derived from Creosote (fig.1) may aid in the treatment of malaria infection. Nordihydroguaiaretic acid (NDGA), by increasing the expression of its target gene, it may: (1) increase iron transporter Ferroportin expression; (2) decrease the negative regulator of iron transporter Ferroportin, hepcidin expression; (3) decrease intracellular iron accumulation; (4) decrease oxidative stress; (5) inhibit cellular damage; (5) prevent hemolysis; and (6) attenuate malarial infection (fig.1). Together, pharmacological formulations encompassing “Nordihydroguaiaretic acid (NDGA) or its analogues, either alone or in combination with other anti-malarial drugs, “ may be used to treat malaria (fig 2.).

Figure 1. Mechanistic insights into how Nordihydroguaiaretic acid (NDGA) may attenuate malaria infection. NDGA, by increasing the expression of its target gene, it may increase ferroportin levels and decrease intracellular iron accumulation. Thereby, it may promote malarial parasite clearance.

Figure 2.  Nordihydroguaiaretic acid (NDGA) functions as an anti-malarial agent through induction of ferroportin.

 


Details of the research findings:

Undisclosed mechanistic information: How Nordihydroguaiaretic acid (NDGA)  increases ferroportin expression

Idea Proposed/Formulated by: Dr L Boominathan Ph.D.

Terms & Conditions apply http://genomediscovery.org/registration/terms-and-conditions/

Amount: $500#

# Research cooperation


References:

Web: http://genomediscovery.org or http://newbioideas.com

Citation: Boominathan, L., Natural product-derived therapy for Malaria: Nordihydroguaiaretic acid (NDGA) increases Ferroportin expression, decreases intracellular iron accumulation, inhibits cellular damage, prevents hemolysis, and inhibits malaria infection, via upregulation of its target gene, 21/April/2018, 7.40 am, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org

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