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Corn husk validated to treat malaria


*Purple grains reduce inflammation, insulin resistance, prevent onset of ulcer
Scientists have confirmed that the husk extract/fractions of corn/maize (Zea mays) possesses antimalarial and anti-plasmodial activities. This justifies its use in ethno-medicine to treat malaria infections.Botanically called Zea mays, corn or maize belongs to the plant family Poaceae. In Nigeria, it is called ka or oka in Edo; ibopot in Efik; oka in Esan; agwado or daawar Masar in Hausa; akpa-akpa in Ibibio; oka in Ibo; oka in Urhobo; and igbado in Yoruba.

Husk (or hull) in botany is the outer shell or coating of a seed. It often refers to the leafy outer covering of an ear of maize (corn) as it grows on the plant. Literally, a husk or hull includes the protective outer covering of a seed, fruit, or vegetable.Anti-plasmodial means something that counters parasites of the genus Plasmodium (Plasmodium falciparum and Plasmodium berghei), which are the common malaria parasites.

The study titled “Antimalarial and anti-plasmodial activity of husk extract and fractions of Zea mays” was published in the journal Pharmaceutical Biology.The researchers include: Okokon J.E.; Antia B.S.; Mohanakrishnan D. and Sahal D.The researchers assessed the antimalarial and anti-plasmodial potentials of the husk extract and fractions on malaria parasites using in vivo and in vitro models.

The ethanol husk extract and fractions (187-748 mg/kg, p.o.) of Zea mays were investigated for antimalarial activity against Plasmodium berghei using rodent (mice) malaria models and in vitro activity against chloroquine sensitive (Pf 3D7) and resistant (Pf INDO) strains of Plasmodium falciparum using the SRBR green assay method. Median lethal dose and cytotoxic activities against HeLa and HEKS cells were also carried out. The GCMS analysis of the most active fraction was carried out.

The results showed the husk extract (187-748 mg/kg, p.o.) with median Lethal Dose (LD50) of 1874.83 mg/kg was found to exert significant antimalarial activity against P. berghei infection in suppressive, prophylactive and curative tests. The crude extract and fractions also exerted prominent activity against both chloroquine sensitive (Pf 3D7) and resistant (Pf INDO) strains of P. falciparum with the ethyl acetate fraction exerting the highest activity with IC50 values of 9.31 ± 0.46 μg/mL (Pf 3D7) and 3.69 ± 0.66 μg/mL (Pf INDO). The crude extract and fractions were not cytotoxic to the two cell lines tested with IC50 values of >100 μg/mL against both HeLa and HEKS cell lines.

IC50 is the half maximal inhibitory concentration is a measure of the potency of a substance in inhibiting a specific biological or biochemical function.

Also, new research suggests that chemicals in purple corn can reduce inflammation and insulin resistance in a mouse cell model.Corn may not be the most obvious choice when looking at managing diabetes. However, this grain comes in a variety of shades and colours, and it is these pigment chemicals that might hold the key to unlocking its potential benefits for people living with diabetes.

A 2017 study showed that rats that ate extracts from a strain of blue corn alongside a Western-style diet had less abdominal fat, better blood cholesterol and triglyceride levels, and lower blood pressure than rats that ate only the Western-style diet.A research team from the University of Illinois at Urbana-Champaign, United States, who worked with collaborators at Northeast Agricultural University and Zhejiang University, both in China, now presents data showing that the complex phytochemicals in a variety of new purple corn strains may reduce inflammation and improve insulin sensitivity in a mouse cell model.

Elvira Gonzalez de Mejia, corresponding author and a professor of food science, led the research, and the team published the findings in the journal Food Chemistry.For the study, the researchers spent four years growing 20 new varieties of corn, which they derived from Apache red maize. They then used water to extract the chemical compounds present in the outer layer of the corn kernels, called the pericarp.

Each pericarp extract had a unique profile of anthocyanins, the pigments that create a corn strain’s particular shade of red-purple, as well as other phytochemicals or phenolic compounds, including caffeic acid, vanillic acid, luteolin, and quercetin among others.To test the potency of each strain’s pericarp extract, the researchers took to the laboratory and used mouse cell models of inflammation and obesity — two critical drivers of diabetes — as well as insulin resistance.

When they exposed macrophages to the extracts, they saw a reduction in pro-inflammatory molecules. Macrophages are immune cells that play a role in inflammation.They also found that some of the extracts were mildly toxic to fat cells but were able to dampen the conversion of precursor cells into mature fat cells called adipocytes, which accumulate fat and drive obesity.The researchers also tested their pericarp extracts on adipocytes that they had artificially induced to develop insulin resistance, a hallmark of diabetes.

The extracts reduced the levels of oxidative stress in the cells, which is a measure of insulin resistance.Glucose uptake increased to varying degrees in the presence of the extracts, according to the study paper, and this demonstrates a reduction in insulin resistance.

The purple corn extracts may provide some additional benefits.Alpha-amylase is an enzyme that plays a role in the process of breaking down complex carbohydrates into simple sugars. Inhibition of the protein in people with diabetes can lead to lower blood sugar levels. The pericarp extracts had a potent inhibitory effect on alpha-amylase.

The extracts also inhibited another enzyme called dipeptidyl-peptidase 4 (DPP-4), which activates hormones that regulate insulin secretion in turn. Pharmaceutical DPP-4 inhibitors are a relatively new class of drug that doctors use to treat type 2 diabetes.Postdoctoral researcher and study co-author, Diego Luna-Vital, said: “We observed very important changes in molecules that reduced oxidative stress and inflammation in the insulin-resistant adipocytes. We also found important changes in pro-inflammatory molecules in the immune cells.”

Medical News Today (MNT) asked de Mejia whether she foresees people with diabetes making use of purple corn by including it in their diet or by taking pericarp extracts. “Both approaches are important,” she explained, “the consumption of the whole coloured corn as part of the diet, and also, the utilization as ingredient of the current pericarp co-product from the dry milling corn processing.”The researchers are continuing their work with the aim of breeding corn hybrids that combine the phytochemicals that showed the most potential in the study.

Another recent study published in Avicenna Journal of Phytomedicine (AJP) has also confirmed the anti-plasmodial activity and cytotoxicity of ethanol extract of Zea mays root.The researchers concluded: “These results suggest that the root extract of Zea mays possesses antimalarial activity against both chloroquine-sensitive and resistant malaria and these data justify its use in ethno-medicine to treat malaria infections.”

The researchers include: Jude Efiom Okokon; Bassey Sunday Antia; Bala Adamu Azare and Patience Jude Okokon. The researchers evaluated Zea mays root decoction that has been traditionally used for the treatment of malaria by various tribes in Nigeria for antimalarial potential against malaria parasites using in vivo and in vitro models.The root extract of Zea mays was investigated for antimalarial activity against Plasmodium berghei in mice using rodent malaria models; suppressive, prophylactic and curative tests and in vitro anti-plasmodial activity against chloroquine-sensitive (Pf 3D7) and resistant (Pf INDO) strains of Plasmodium falciparum using SYBR green assay method. Median lethal dose and cytotoxic activity against HeLa and HEKS cells were assessed and phytochemical screening was also carried out using standard procedures.

The LD50 value of root extract was found to be 474.34 mg/kg. The crude extract (45-135 mg/kg, p.o) showed significant (p<0.05-0.001) antimalarial activity against P. berghei infection in suppressive, prophylactic and curative tests with a prolonged survival time. The crude extract also showed moderate activity against both chloroquine-sensitive (Pf 3D7) and resistant (Pf INDO) strains of P. falciparum with an IC50 value of 71.62±3.38 μg/ml (for Pf 3D7) and 63.76±4.12 μg/ml (for Pf INDO). The crude extract was not cytotoxic to the two cell lines tested with TC50 of >100 μg/ml against both HeLa and HEKS cell lines.Yet another study published in African Journal of Pharmacology and Therapeutics has validated anti-ulcerogenic activity of husk extract of Zea mays.

Anti-ulcerogenic means preventing the onset of ulcers.The researchers include: Jude E. Okokon; Jackson Obot; and Louis U. Amazu.Zea mays husk is used in Ibibio traditional medicine for the treatment of various ailments including diabetes mellitus, malaria and ulcer.The researchers evaluated the ethanol husk extract of Zea mays (187-784 mg/kg) for antiulcerogenic activity against indomethacin, ethanol and histamine-induced ulcers in rats.

The husk extract was found to significantly inhibit ulcers induced by indomethacin, ethanol and histamine in a dose-dependent fashion.They concluded: “These results suggest that the husk extract of Zea mays possess anti-ulcerogenic potentials which are due to the activities of the phytochemical constituents.”Besides its nutritive values, maize grains, leaves, corn silks, stalk, and inflorescence are also used in ethno-medicine for the treatment of several ailments. The corn silk is used as an anti-diabetic diuretic, and decoction of the silk is consumed for the treatment of urinary problems and gallstones. The ash of the cob is used for the treatment of cough as well as inflammatory diseases. The husks are used in the treatment of pains and arthritis. It is also taken as warm tea for the treatment of malaria in Ibibio traditional medicine.

Biological activities reported on the leaf extract include anticancer, antioxidant and anti-oxidative stress activities. Anti-inflammatory and analgesic activities have been reported on the husk extract. Eight phenolic compounds (gallic acid, protocatechuic acid, chlorogenic acid, cafeic acid, femlic acid, rutin, resveratrol, and kaempferol) have also been detected in ethanol extract of Z. mays husk. Phytochemical compounds with antifungal activity such as 6-methoxybenzoxazolinone and 6,7-dimethoxybenzoxazolinone, and (6R)-7,8-dihydro- 3-oxo-α-ionone and (6R; 9R)-7,8-dihydro-3-oxo- α -ionol were isolated from root extract and root exudates of Z. mays.

The researchers noted: “… It was found that the extract significantly reduced the parasitaemia in prophylactic, suppressive and curative models in a dose-dependent fashion. However, the root extract only exerted moderate activity against chloroquine-sensitive P. falciparum (3D7) strain and chloroquine-resistant strain (INDO). The variability in the activity of the root extract in both in vivo and in vitro studies, suggests the involvement of immune system in the activity of the root extract, which could probably be immuno-stimulation. It further suggests that this plant may either be an immune stimulant or it may alleviate the symptoms of malaria such as pains and fever among others. Kirby (1997) had reported that some plants that are locally used as malarial remedies may only alleviate the symptoms associated with malaria without having any significant effect on the parasites as shown in this study.

“Moreso, plant compounds that suppress or partly inhibit the growth of the parasite (plasmodistatic) as well as those that stimulate the immune system or provide symptomatic cure and reverse some pathological features of malaria infection are reported to potentiate malaria resistance and anti-plasmodial activity in immune individuals living in endemic areas. Therefore, this plant may help the immune system to develop resistance to malaria and in a way, antimalarial activity.

“Some secondary metabolites of plants such as alkaloids, terpenes and flavonoids have been reported to have anti-plasmodial activity. These compounds were found to be present in the extract studied and may be responsible for the observed anti-plasmodial activity of the extract, though the active principle is yet to be identified. Although the mechanism of action of this extract has not been elucidated, flavonoids are known to exert anti-plasmodial activity by chelating with nucleic acid base pairing of the parasite, thereby producing plasmocidal effects. Other modes of action of flavonoids include modulation of host immunity to tackle disease and inhibition of plasmodial enoyl-ACP reductase (FAB I enzyme), a key regulator of type II fatty synthases (FAS-II) in P. falciparum. Flavonoids may also bind parasite’s serine/threonine kinase with high affinity and affect its development. Also, some plants are known to exert anti-plasmodial action either by causing elevation of red blood cell oxidation or by inhibiting protein synthesis. The extract may be acting through one of these mechanisms to exert anti-plasmodial activity observed in this study.

“Maize plant is known as a rich source of phenolics with antioxidant potentials. Some of these phenolic compounds like gallic acid and rutin present in Zea mays parts have been reported to possess antimalarial activity. Rutin has been shown to possess significant anti-plasmodial activity against chloroquine-sensitive and resistant strains of P. falciparum with IC50 of 3.53±13.34 µM against 3D7 and 15.00 µM against K1.

“Besides, antioxidant potentials of some plant and natural products especially flavonoids have been found to promote schizoniticide activity by modulating the cellular signaling pathway and this has been suggested to be responsible for anti-plasmodial activity of compounds such as quercetin, as elevated free radicals levels are common features of malaria disease and are implicated in severe malaria complications. This could be one of the modes of action of this extract as it contains antioxidant phenolics and flavonoids. 6-methoxybenzoxazolinone, 6, 7-dimethoxybenzoxazolinone, (6R)-7,8-dihydro- 3-oxo-α-ionone and (6R; 9R)-7,8-dihydro-3-oxo- α -ionol have been isolated from the root extract and exudates of Zea mays. These compounds from the root may likely possess anti-plasmodial activity.

“In this study, the root extract of Zea mays was also found to contain terpenes among others. Terpenes and their derivatives such as monoterpenes and sesquiterpenes have been implicated in anti-plasmodial activity of many plants. Monoterpenes such as limonene have been implicated in endo-peroxidation leading to plasmocidal activity. These may also contribute to the anti-plasmodial activity of this extract.“The result obtained in this study indicated that the root of plant possesses a significant anti-plasmodial activity in in vivo and in vitro models which justifies the usage of this plant in the treatment of malaria.”

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Corn huskmalaria
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