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Local cherry as intermittent preventive therapy against malaria in pregnancy

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*Plant could be used for treatment of HIV, heart disease, stroke, diabetes, toothache, rheumatic pain, cancer
Nigerian researchers have shown that both the seed and pulp of African star apple or local cherry, Chrysophyllum albidum, possess both suppressive and curative anti-malaria property.

The scientists demonstrated the presence of antimalarial constituents in the chemically uncharacterized samples (fruit pulp and seed) of wild star apple, which may be valuable in pregnancy where it may possibly serve as an intermittent preventive therapy (IPT) against malaria.

According to the study published in journal Ancient Science of Life, the sampled plant parts can be used for treatment and prevention of malaria both in pregnant and non-pregnant individuals.

The study titled “Traditional Consumption of the Fruit Pulp of Chrysophyllum albidum (Sapotaceae) in Pregnancy may be Serving as an Intermittent Preventive Therapy against Malaria Infection”

The researchers include: Chibueze Peter Ihekwereme, Frances Kaosiso Okoye, Sandra Chinenye Agu, and Angus Nnamdi Oli.

Botanically called Chrysophyllum albidum, African star apple, which belongs to the plant family Sapotaceae is an edible tropical fruit known by various tribal names. It is called Utieagadava in Urhobo, Agbalumo in Yoruba, Udara in Ibo, Efik and Ibibio, Ehya in Igala, Agwaluma in Hausa tribes of Nigeria.

African star apple is used in traditional folklore medicine to cure various diseases. It is used traditionally as an antiseptic, anthelmintic, mosquito bite repellent, for stomach ailments, tonic, antiscorbutic, astringent, diuretic, headache, arthritis, and digestive and appetite stimulant, an anti-oxidant and for colds, coughs and sore throats.

In the last two decades, Chrysophyllum albidium has been subjected to extensive phytochemical, pharmacological and clinical investigations and many interesting outcomes in the areas of insecticidal activity, anthelmintic (worm expeller), anti-osteoporosis (treatment brittle bone disease), radical scavenging, anti-cholinesterase, cardiac diseases, anticancer, antimicrobial, eye conditions, inflammatory bowel disease and improved lung function have been reported.

Earlier studies published by The Guardian showed extracts of African star apple or local cherry as ‘cure’ for drug-resistant infections and malaria. African star apple had also been validated to reduce blood sugar, cholesterol and in treatment of ulcer, diarrhoea, wound healing, among others.

Indeed, the pulp of the fruit is commonly consumed by all in South East Nigeria, especially pregnant women. The leaves are frequently used to treat malaria, blood pressure, anemia, skin eruptions, diarrhea and stomach ache.

The roots are used in the treatment of sterility, sexual asthenia, and asthma; while its seeds are mostly used to treat intestinal worms and haemorrhoids.

The bark is used against cough, icterus, yellow fever and also malaria, while the fruit is used for the treatment of dental decay.

Eleagnine, an alkaloid isolated from C. albidum seed cotyledon has been reported to have antinociceptive, anti-inflammatory and antioxidant activities.

Antinociceptive is the action or process of blocking the detection of a painful or injurious stimulus by sensory neurons.

Studies have shown that the leaf extract of C. albidum contains antiplatelet, hypoglycemic, and antibacterial compounds. The methanol bark-extract contains antiplasmodial substances.

Meanwhile, malaria has been shown to affect fertility, population growth, savings and investment, worker productivity, absenteeism, premature mortality and medical cost. Malaria primarily affects human health especially in pregnancy where it is detrimental to both mother and unborn child.

Commonly, malaria causes anemia in the mother, and low birth weight in the fetus. The risk inherent from untreated malaria in pregnancy outweighs the adverse effects arising from treatment. Plasmodium falciparum causes more maternal and fetal morbidity and mortality than non-falciparum infections.

IPT is the administration of antimalarial doses to pregnant women in malaria endemic countries who have not shown obvious signs of malaria infection. Such women are given full curative regimen whenever malaria is evident. Generally, treatment of severe malaria includes parasite clearance and supportive measures such as monitoring of blood sugar and potassium levels, as well as management of high fever and the seizures it may provoke. Antimalarial resistance and treatment costs are among the current issues that necessitate an urgent need for malaria control especially in endemic regions.

According to the researchers, the concept behind this study is that the discovery of antimalarial constituents in the bark of C. albidum could be a pointer that the fruit pulp, commonly consumed by pregnant women may also have anti-plasmodial property. This preliminary study, therefore, was designed to investigate the presence of antimalarial principles in the pulp juice and seed of the plant.

The researchers wrote: “The result of our study shows that both the seed and pulp possess both suppressive and curative anti-plasmodial property. Previously, methanol bark extract of C. albidum was reported to suppress early plasmodial infection (per oral) by 74.20 per cent and 62.90 per cent at 1000 and 1500 mg/kg/day respectively. Reported percentage reductions for the curative tests on Day 7 were 82.86 per cent, 97.14 per cent, and 77.14 per cent at 750, 1000 and 1500 mg/kg respectively. On comparison with equal doses (at 1000 mg/kg/day), it becomes obvious that both the ethanol seed extract (97.30 per cent) and the pulp juice (81.08 per cent) have higher chemo-suppressive potency than the methanol bark extract (74.20 per cent).

“On the curative effect, the result from the bark (97.14 per cent) is comparable with that of seed extract (94.87 per cent) and the pulp juice (92.31 per cent). Even though the statistical relevance of the comparison between our results and the previously published data remains to be verified, our results seem to suggest the seed has more antimalarial principles than the pulp.

Interestingly, when the positive control was statistically compared with either the pulp or seed at 500 mg/kg, it was observed that there were no significant differences suggesting that the plant material was as effective as the control.”

The researchers added: “The sampled plant parts can be used for treatment and prevention of malaria both in pregnant and non-pregnant individuals. It also shows the plant has a potential of serving as IPT against malaria in pregnancy. Pregnancy predisposes to malaria infection, and IPT was initiated to control the menace of the infection to both the mother and the unborn child. Traditional consumption of the pulp by pregnant women does not suggest any harm to the mothers or their babies.

“Also, the results of the oral acute toxicity test show the pulp to be considered safe. This opinion is strengthened by the experience of the consuming public since they have not associated it with any untoward effects. Conversely, Lethal Dose (LD)50 of the plant methanol bark extract in mice was calculated to be 1850 mg/kg intraperitoneal, suggesting the bark might be toxic at clinically effective doses. Perhaps, this may also offer some explanation why the methanol bark extract demonstrated a higher antimalarial activity at a lower oral dose of 1000 mg/kg/day, than at 1500 mg/kg/day per oral. Irrespective of the above, it is still necessary to scientifically establish safety using appropriate pharmacological models.”

According to the study, phytochemicals present in both the ethanol seed extract and the expressed juice from the pulp include alkaloids, flavonoids, cardiac glycosides, and tannins. In addition, the ethanol seed extract also revealed the presence of saponins and steroids.

Previous studies found alkaloids, anthraquinones, saponins, cardenolides and tannins in the leaf, stem and bark of the plant. Alkaloids, flavonoids, triterpenoids, and saponins have been associated with antimalarial property. Saponins are detergents and might alter cell membrane properties of protozoans through their surface activity. Alkaloids are a major class of compounds possessing antimalarial activity; quinine is one of the most important and oldest antimalarial drugs.

Eleagnine, tetrahydro- 2 – methylharman and skatole have been isolated from the seeds of C. albidum. Eleagnine, an alkaloid has antimicrobial, antinociceptive, anti-inflammatory and antioxidant activities.

According to the researchers, the compounds responsible for the activity may possibly have short half-lives. “A comparison of the level of suppression on Day 4 and Day 7 shows no statistical difference suggesting there was no continued activity after Day 4. Drugs with long half-lives such as Mefloquine, Pyrimethamine, Piperaquine, and Lumefantrine continue to act many more days even after discontinuation of treatment,” they said.

The researchers concluded: “There are two key conclusions of this study. Consumption of the fruit pulp should be encouraged especially in pregnancy. Secondly, it provides an avenue to explore possibilities of obtaining an antimalarial drug molecule.

“This study demonstrates the presence of antimalarial constituents in chemically uncharacterized samples (fruit pulp and seed) of C. albidum. The fruit pulp, seeds, and bark of the plant have antimalarial property. Consequently, consumption of the fruit pulp by pregnant women may offer some protection against malaria, and may possibly serve as IPT against the infection. Furthermore, these findings suggest these plant parts have the potential for isolation of lead compounds from their extracts. Hence, further studies should be carried out on the plant to harness its antimalarial property.”

Another recent study published in Journal of Biomedical and Pharmaceutical Sciences evaluated the antimalarial and liver function potentials of Chrysophyllum albidum stem bark.

The researchers from the Department of Biochemistry, School of Life
Sciences, Federal University of Technology Minna, Niger State, evaluated the antimalarial potentials of methanol extract of the stem bark of C. albidum and specific Alkaline phosphatase (ALP), Alanine transaminase (ALT) and Aspartate transaminase (AST) activities in both sera and livers of Plasmodium berghei infected mice treated with methanol extract of C. albidum stem bark.

The result of the phytochemical screening indicated the presence of anthraquinones, steroids, tannins, alkaloids, glycosides, terpenoides, flavonoids, saponins and phlobatannins.

Percentage parasite inhibition was calculated to be 56.97 per cent, 74.10 per cent, 85.26 per cent and 92.83 per cent for groups treated with 200 mg/kg, 400 mg/kg, 600 mg/kg body weight of the methanol extract of C. albidum stem bark and 5 mg/kg body weight of Chloroquine (standard drug) respectively.

It was observed that, the specific ALP, ALT and AST activities in both sera and liver samples of the group infected but not treated were significantly higher than the infected and treated groups. There was significant difference in the specific ALP, ALT and AST activities between groups treated with 5 mg/kg body weight of Chloroquine and 600mg/kg body weight of the methanol extract of
C. albidum stem bark. However, there was no significant difference (p˃0.05) in the specific ALP, ALT and AST activities between the groups treated with 200 mg/kg and 400mg/kg body weight of methanol extract of C. albidum stem bark.

The ability of the methanol extract of C. albidum stem bark to inhibit parasite multiplication/progression may be attributed to the presence of various bioactive constituents such as flavonoids, tannins, alkaloid or saponins and further support the ethno medicinal claim of the use of other parts of the plant in the treatment of malaria.

Plant extracts are one of the most attracted sources of new drugs for the treatment of liver disease. Evidences have shown that antioxidants derived from plant sources may be useful in preventing the deleterious consequences of oxidative stress and there is increasing interest in the hepato-protective potentials of natural antioxidants contained in spices, herbs and medicinal plants.

A considerable amount of natural antioxidant agent including alkaloid, saponin, xanthones, triterpenes and tannins has been isolated from medicinal plant. On the array of medicinal plant with hepato-protective potential, is Chrysophyllum
albidum.

It was observed from this study that, methanol extract of C. albidum stem bark was most effective at a dose of 600mg/kg body weight. It has been well established that plants whose phytochemical compounds include anthraquinones, alkaloids and saponins may have antimalarial activities. These established findings are similar to those obtained in this study as methanol extract of C. albidum stem bark was found.

Yet another recent study by researchers from the Department of Chemical Science, Federal University, Wukari Nigeria and Department of Chemistry, Abubakar Tafawa Balewa University Bauchi, found that based on the presence of β-amyrin acetate in C. albidum, the plant could be a viable source of antioxidant and cytotoxic agents in cancer chemotherapy in the near future. C. albidum may also be used for the treatment of malaria, acquired immunodeficiency syndrome, heart disease, stroke, arteriosclerosis, diabetes, toothache, rheumatic pain, and other inflammatory related disorders and cancer because of the β – amyrin acetate.

The study was published in the Journal of Chemical Society of Nigeria.

They concluded: “It can be concluded that the structural elucidation by spectroscopic methods (IR,1H NMR, 13C and NMR) of C. albidum yielded a compound characterized as β –amyrin acetate. The beta-amyrin acetate has use as anticancer, antiparasitic, antispasmodic, antihyperglycemic and as herbicide, fungicide and antibiotic in medicines. α, β- amyrin has the potential to combat acute pancreatitis by acting as an anti- inflammatory, antioxidant agent cytotoxic and anticancer properties.

“The antioxidant activity of can be attributed to the beta- amyrin acetate (-amyrin acetate). It may be stated that the result of the present study demonstrated new property of -AA as a potent lipid-lowering agent. The plant extracts could therefore be seen as a potential source for useful drug and this justifies the claims by the traditional healers that the C. albidium leaves are used to cure some illness. The continued traditional medicinal use of these plants is therefore encouraged.”

The study is titled: “β – amyrin-3- acetate Detected in Methanolic Leaf Extract of Chrysophyllum albidium.”


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