The search for better antimalarials is ongoing all over the world. But Nigerian researchers have made giant strides in recent times with the discovery and validation of local plants that are comparable to the World Health Organisation’s (WHO’s) endorsed Artemisia annua (Artemisinin-based Combination Therapy, ACT) in terms of efficacy and safety. CHUKWUMA MUANYA writes.
MALARIA is here with us. It is associated with high mortality and morbidity especially among children under five and pregnant women.
Plant based therapies have held the ace in the treatment of malaria from chloroquine obtained from the Quinine bark also called Cinchona tree to the artemisin from the Chinese salad plant, Artemisia annua.
Unfortunately, the malaria parasite, Plasmodium falciparum, has began to develop resistance to the WHO endorsed treatment ACT, made from Artemisia annua.
However, Nigerian researchers have continued to identify and validate local plants that are equally safe and efficacious as the Chinese salad plant.
Indeed, the resistance of human malaria parasites to anti-malarial compounds such as chloroquine, quinine, amodiaquine, mefloquine, sulphadoxine/pyrimethamine, and artemisinin has become considerable concern, particularly in view of the shortage of novel classes of anti-malarial drugs. Researchers say one way to prevent resistance is by using new compounds that are not based on existing synthetic antimicrobial agents.
A recent study has identified medicinal plants, such as Momordica charantia, Momordica balsamina, Ageratum conyzoides, and Diospyros monbuttensis to be very efficacious in the treatment of drug resistant malaria.
Momordica charantia also called bitter melon belongs to the plant family Cucurbitaceae. In Nigeria, bitter melon is called ndakdi in Dera; dagdaggi in Fula-Fulfulde; hashinashiap in Goemai; daddagu in Hausa; iliahia in Igala; akban ndene in Igbo (Ibuzo in Delta State); dagdagoo in Kanuri; akara aj, ejinrin nla, ejinrin weeri, ejirin-weewe or igbole aja in Yoruba.
Momordica balsamina also called balsam apple also belongs to the plant family Cucurbitaceae. In Nigeria, it is called ndákďì in Dera, dagdaggi in Fulani, daddagu in Hausa, akban ndene in Igbo (Ibusa), dagdago in Kanuri, garahanu in Mbula and ejirin in Yoruba.
Commonly called goat weed and billy goat weed, Ageratum conyzoides belongs to the plant family Asteraceae (formerly Compositae). It is native to Central America, Caribbean, United States, Southeast Asia, South China, India, Nigeria, Australia, and South America.
Ageratum conyzoides is traditionally called ufu opioko and otogo by the Igedes in Benue state, Nigeria. In Southwestern Nigeria, it is known as Imí esú. It is called ebegho-edore in Edo, ikoun ifuo eyen in Efik, agadi isi awa in Ibo, huhu in Tiv, ako yunyun in Yoruba.
Popularly known as Yoruba ebony or walking stick ebony, Diospyros monbuttensis belongs to the family Ebenaceae. It is called okpu ocha in Igbo; egun eja egungunekun, erikesi (pig’s teeth), ògàn, ògàn-ègbò, ògàn-pa or ogan-pupa (red ogan) in Yoruba.
The study titled “In vitro studies on the sensitivity pattern of Plasmodium falciparum to anti-malarial drugs and local herbal extracts” was published in Malaria Journal.
The 2014 study was conducted by Indian and Nigeria researchers from the Department of Biological Sciences, Covenant University, Ota, Ogun State; Department of Medical Parasitology, Ladoke Akintola University of Technology (LAUTECH) Teaching Hospital, Osogbo, Osun State; Department of Botany, University of Ibadan, Ibadan, Oyo State; and National Institute of Malaria Research, New Delhi, India.
The researchers concluded: “Natural products isolated from plants used in traditional medicine, which have potent anti-plasmodial action in vitro, represent potential sources of new anti-malarial drugs.”
A total of 4,066 subjects comprising 1,839 males and 2,227 females presenting with malaria in four different zones of Ogun State were recruited into the study. The total number of subjects recruited in Sango-Otta, Abeokuta, Ijebu-Ode and Sagamu were 1,120, 1,116, 995 and 835, respectively. Children between one and 15 years, pregnant women and other adults were included in this study. This is because the majority of malaria cases occur in children under the age of 12 years; pregnant women are also especially vulnerable. The mean age was 19 years, with 93 per cent less than 25 years old.
Scientific and ethical clearance for this work was obtained from the Nigerian Institute of Medical Research – Institutional Review Board (NIMR-IRB) and Covenant University Ethics Committee. The Ogun State Ministry of Health (Hospitals Management Board) was also informed and clearance obtained for this study. Written informed consent was obtained from patients prior to recruitment into this study. Consent for children was provided by parents/guardians while some participants provided the assents.
The results of the study showed sensitivity of 100 Plasmodium falciparum isolates to chloroquine, quinine, amodiaquine, mefloquine, sulphadoxine/pyrimethamine, artemisinin, Momordica charantia, Diospyros monbuttensis and Morinda lucida.
Morinda lucida belongs to the plant family Rubiaceae. It is commonly called Brimstone tree. It is oruwo or erewo in Yoruba, eze-ogu or njisi in Igbo.
The researchers said all the isolates tested were sensitive to quinine, mefloquine and artesunate. Fifty-one percent of the isolates were resistant to chloroquine, 13 per cent to amodiaquine and five per cent to sulphadoxine/pyrimethamine. Highest resistance to chloroquine (68.9 per cent) was recorded among isolates from Yewa zone while highest resistance to amodiaquine (30 per cent) was observed in Ijebu zone. Highest resistance to sulphadoxine/pyrimethamine was recorded in Yewa and Egba zones, respectively. A positive correlation was observed between the responses to artemisinin and mefloquine, artemisinin and quinine and quinine and mefloquine. A negative correlation was observed between the responses to chloroquine and mefloquine. Highest anti-plasmodial activity was obtained with the ethanolic extract of D. monbuttensis while the lowest was obtained from M. lucida.
They wrote: “In this study, three crude organic extracts obtained from medicinal plants used in Nigerian folk medicine for the treatment of fever and malaria were tested in vitro against P. falciparum. Diospyros monbuttensis showed appreciable inhibition to the parasites at all the concentrations used and an IC50 of 3.2 nM in the study. Diospyros monbuttensis, which is locally used for the treatment of fevers, headaches and stomach disorders, has not been widely studied. This study represents the first conducted for anti-malarial activity of crude extracts of D. monbuttensis. The results confirm that these plants, which are used in traditional medicine against malaria, may possess in vitro and significant anti-malarial potential and justify their use in traditional medicine. This observation suggests that the active constituents in the extract may be cytotoxic for P. falciparum trophozoites, thereby inhibiting their development to the schizont stage.
“An IC50 observed for M. charantia in this study was 12.5 nM. These observations suggest that the active constituents in the extract might also be cytotoxic for P. falciparum trophozoites, thereby inhibiting their development to the schizont stage. The anti-malarial activity of M. charantia has been previously reported. They found that the aqueous extract of M. charantia leaves showed IC50 values less than 100 μg/ml which is in agreement with the observations in this study; the methanolic extract showed moderate activity with IC50 = 12.5 nM.
“Morinda lucida also exhibited anti-malarial activity in this study. The IC50 of 25 nM observed in this study is comparable with other studies. Also for M. lucida, dose-dependent inhibitory outcomes were marked. Awe and Makinde, reported the dose-dependent and seasonal variation in the activity of M. lucida using both in vitro and in vivo techniques. Morinda lucida was reported to contain anthraquinones, which showed in vitro activity against P. falciparum and also possess antifungal properties. Morinda lucida is used locally in the treatment of yellow fever and jaundice.”
The IC50 is a measure of how effective a drug is. It indicates how much of a particular drug or other substance is needed to inhibit a given biological process (or component of a process, that is an enzyme, cell, cell receptor or microorganism) by half.
According to the researchers, it had been advocated that direct crude drug formulation of the herbs following toxicological absolution (after it has been ascertained to be non-toxic) may not only produce dosage forms faster but will also lead to cheaper and more affordable drugs for the communities that need them. This research was carried out in order to increase the database of plants whose extracts can be used in the treatment of malaria.
The researchers wrote: “The urgency generated by drug-resistant strains of malaria parasites has accelerated anti-malarial drug research over the last two decades. While synthetic pharmaceutical agents continue to dominate research, attention has increasingly been directed to natural products. The success of quinine (QN) and artemisinin, isolated from Artemisia annua and its derivatives, for the treatment of resistant malaria has focused attention on plants as a source of anti-malarial drugs.
“Moreover, plants have been the basic source of sophisticated traditional medicine systems for thousands of years and were instrumental in early pharmaceutical drug discovery and industry. The world’s poorest are the worst affected, and many treat themselves with traditional herbal medicines. These are often more available and affordable, and sometimes are perceived as more effective than conventional anti-malarial drugs.
“Ethnobotanical information about anti-malarial plants used in traditional herbal medicine is essential for further evaluation of the efficacy of plant anti-malarial remedies, and efforts are now being directed towards discovery and development of new, chemically diverse anti-malarial agents. Several rural dwellers depend on traditional herbal medicine for treatment of many infectious diseases. The reputed efficacies of these plants have been experienced and passed on from one generation to the other.
“About 75 per cent of the population in Africa does not have direct access to conventional medicine for malaria treatment but they do have access to traditional medicine for treating fevers. Treatment with these remedies has suffered a number of deficiencies; identification of plant extracts may be insecure and the chemical content of extracts may vary considerably.”
Meanwhile, Ageratum conyzoides has been used in folklore for the treatment of fever, pneumonia, cold, rheumatism, spasm, headache, and curing wounds. It is gastro-protective, antibacterial, anti-inflammatory, anti-analgesic, antipyretic, anticoccidial, and anticonvulsant properties have been reported.
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According to The Useful Plants of West Tropical Africa by H. M. Burkill, “the leaves of Ageratum conyzoides are considered to be antiseptic. Preparations are commonly applied to craw-craw in the Region, and to itch in South East (SE) Asia. In Congo the sap is put onto prurient affections of the skin. The leaves are cicitrisant. They are applied to chronic ulcers, to bruises, cuts and sores, and circumcision wounds in Nigeria; to cuts and sores in Gabon, Tanganyika and in Ethiopia; as a haemostatic topically on wounds and haemorrhoids and intra-vaginally for uterine bleeding in Ivory Coast.
“The sap or the plant, dried and powdered, is a wound-dressing in Tanganyika, and is valued especially for burns; similar uses are recorded in SE Asia. The leaves may have some analgesic action: powdered leaves are applied to the forehead for headache in The Gambia; the whole green leaf is so used in Nigeria; the sap in Congo, and mixed with clay in Ivory Coast-Upper Volta for headache and chest-pains. Leaves baked in palm-oil are used for rheumatism in Gabon.”
According to The Useful Plants of West Tropical Africa by H. M. Burkill, “ A decoction of the bark and twigs, with the leaves of Senna occidentalis (Leguminosae: Caesalpinioideae) and Lippia adoensis (Verbenaceae), is taken in draught and put into baths by the Baule and Anyi of Ivory Coast as a leprosy treatment. They also consider this to be good for fever-pains, stomachache and oedemas. The leaves are used by the Akye to treat chicken-pox.
“The branches, particularly on the younger plants, are armed with short thick spines, to which perhaps the Yoruba name pig’s teeth refers. These are made into an infusion in S Nigeria, which is given, probably on the premise of sympathetic magic, to alleviate teething pains in children. The buds (? flower-buds) are put into soup in S Nigeria, and the fruit has unspecified medicinal application. Examination of the roots of Nigerian material failed to show the presence of any alkaloid.”
According to Burkill, the whole plant of Momordica balsamina is used as a bitter stomachic, an emetic and a purgative. The Useful Plants of West Tropical Africa reads: “The Fula of Senegal use it as a vermifuge. Juice expressed from the leaves is taken by Yoruba for roundworm (Ascaris) and given to children for threadworm. It is an ingredient of the Yoruba agbo pot. A macerate of the whole plant, to which salt is added, is used in Senegal as a galactogogue by draught, and by massage to the chest. This latter application serves also to treat intercostal pains.
“Fula herdsmen in Senegal also use this preparation to increase milk-yield of cows. An infusion is used in the Region as a wash for fever and for yaws, and for these affections a decoction with natron added is taken internally. This preparation is used for horses. The Fula of Senegal ascribe tranquillizing properties to the plant, which are of benefit in cases of mental illness. Zulu of South Africa make an infusion or decoction as a sedative for an irritable stomach. Notwithstanding the emetic and purgative properties, leaves, and sometimes the fruit, are eaten in sauces and soups in the Region. In Jebel Marra of Sudan the leaves serve as a vegetable, and the Pedi of S Africa eat the young leaves as a pot-herb though they recognize the fruit as being deadly poisonous.
“The Kanuri of N Nigeria are said to relish the bitter taste. Consumption though is thought to be less as a foodstuff than as of a vehicle for its medicinal properties, as, for example, its inclusion together with other drug-plants in a Hausa food called fatefate. A trace of alkaloid has been detected in the leaves. Donkeys, cattle, sheep and goats are recorded as grazing the plant in Senegal, but not horses. Feeding trials on sheep in N Rhodesia produced no ill effects. The leaves can be used to clean metals, and leaves and fruit give a lather in water and are used as soap in N Nigeria. It can be used for washing the hands and body but not clothes.
“The fruit mixed with any bland oil can be made into a drawing ointment for festers, inflammations, swellings, yaws, burns, etc. A bitter principle, momordicin, is present. In U.S.A. compounded with olive or almond oil it has been used for chapped hands and for piles, and as a salve on open sores of long standing. The fruit is emetic and cathartic. The seed soaked in water and then inserted in the neck of the womb is a method of producing abortion practiced by the Mbula tribe of N Nigeria. The plant is also added to Stropanthus arrow-poisons by Benin tribes.
“The fruit is thought to have caused poisoning of pigs in Queensland, but nevertheless the seed is said in Australia to be edible after steeping in salt water and cooking. The root is sometimes an ingredient of aphrodisiac prescriptions, and, as are the fruit seeds, is used as an abortifacient. The leaves are put in water for ceremonial washing after digging a grave amongst the Ngizim in Bornu.”
Meanwhile, another study published in Malaria Journal supports the use of Salacia nitida (enyim ocha in Igbo), Nauclea latifolia (ovoro ilu in Igbo) and stem bark of Enantia chlorantha (Erumeru in Igbo).
The study is titled “Antimalarial Activities of Some Selected Traditional Herbs from South Eastern Nigeria Against Plasmodium Species.”
The study investigated three plants traditionally used in the treatment of malaria in the Southeastern part of Nigeria to determine their efficacies as antimalarial compounds. The three herbs were collected through a traditional herbalist who uses them in his practice. Ethanolic extracts from the roots of Enyim ocha (Salacia nitida), Ovoro ilu (Nauclea latifolia) and stem bark of Erumeru (Enantia chlorantha Oliv.) were assessed for antimalarial activity against chloroquine sensitive Plasmodium berghei in mice using the four day suppressive test procedure.
According to the researchers, the extracts had intrinsic antimalarial properties that were dose dependent. The comparison analysis indicated that 250 mg kg-1 body weight of the root of S. nitida produced 71.15 per cent suppression of parasitaemia and the 500 mg kg-1 body weight of the stem bark of E. chlorantha, roots of S. nitida, N. latifolia and the three herbs combined, produced 75.23, 73.28, 71.15 and 77.46 per cent, respectively, compared with chloroquine with 71.15 per cent suppression. The results were significant at p< 0.05 when compared to a placebo and support the traditional use of these plants for the treatment of malaria.
Commonly called African peach or African pincushion tree, Nauclea latifolia belongs to the Rubiaceae family. In Nigeria, it is called Ebeyesi in Yoruba, Ubuluinu in Igbo and Tafashiya or Marga in Hausa.
Nauclea latifolia is a small straggling shrub that is abundant throughout sub-Saharan Africa especially in the tropical rain forest in Nigeria. In traditional medicine, the plant is used to treat different pathologies including epilepsy, fevers, malaria, and pain.
Enantia chlorantha belongs to the plant family Annonaceae. It is locally known as Awogba, Oso pupa or Dokita igbo (Yoruba), Osomolu (Ikale), Kakerim (Boki) and Erenba-vbogo (Bini).
The researchers concluded: “The development of antimalarials from indigenous plants depends to a large extent on the screening of appreciable number of these herbs, particularly those that have been in use by the indigenous people from different geographical areas, especially, from the different tribes where they are endowed by nature. Once the preliminary anti plasmodial effect has been established, further studies to ascertain the active ingredients that exert these effects could then be carried out. This will ultimately help in discovering potent and novel antimalarials to counter the threat posed by malaria in recent times.
“There is increasing concern by medical practitioners as the resistance of malaria parasites to available drugs continues to grow, increasingly limiting our ability to control this serious disease. However, it is reassuring that many new approaches to antimalarial drug discovery are now under evaluation as carried out in this research. Recent increases in the pace of progress in the search especially in the area of herbal medicine, suggest that, if support for antimalarial drug discovery is adequate, the development of novel, but potent antimalaria is underway.
“From the present study, it can be concluded that the ethanolic extracts of the roots and stem bark of N. latifolia, S. nitida and E. chlorantha have shown parasite suppressive effects on P. berghei-infected albino mice in a dose-related fashion. This result therefore, offers a scientific basis for the traditional use of these herbs separately and in combination against malaria parasite. Further studies on the herbs, especially on the refined extracts, to among other things, assess their pharmacokinetic properties, is recommended.”
Yet another study has validated antimalarial activity of ethanolic stem bark extract of Alstonia boonei in mice.
Commonly called pattern wood and stool wood, Alstonia boonei belongs to the plant family Apocynaceae. It is called ofem in Bembi, bokuk in Bokyi, ukhu in Edo, ebo in Efik, etiap in Ejagham, oguk in Ejagham-Etung, uguwa in Engenni, ano in Igala, egbu in Igbo, okugbo in Isekiri, ukpukuhu in Urhobo, ahùn, ako-ibepo, àwiń, or awùn in Yoruba.
The researchers wrote: “Alstonia boonei is a medicinal plant used widely in Nigeria for the management of malaria and other ailments. The aim of the present study was to investigate in vivo antiplasmodial effect in mice. Oral acute toxicity of the ethanolic stem bark extract of Alstonia boonei was evaluated in mice using modified Lorke’s method and the in vivo anti-plasmodial effect against early infection, curative effect against established infection and prophylactic effect against residual infection were studied in chloroquine-sensitive Plasmodium berghei berghei NK65-infected mice.
“The oral median lethal dose of the extract in mice was determined to be greater than 5000 mg kg-1 body weight. The extract at all the doses (100, 200 and 400 mg kg-1, p.o.) used, produced significant (p<0.05), dose-dependent activity against the parasite in the suppressive, curative and prophylactic tests. These results showed that Alstonia boonei ethanolic stem bark extract possesses potent antimalarial effects and may therefore offer the potential for a safe, effective and affordable antimalarial phytomedicine.”
Earlier studies have also suggested that Alstonia boonei and some other plants namely S. latifolius, Petivera alliacea, Mangifera indica and Khaya grandifolia have significant antimalarial properties. However, few reports exist in the literature on the antimalarial activity of ethanolic stem bark extracts of A. boonei. Olajide et al. reported that the stem bark of A. boonei has anti-inflammatory, antipyretic and analgesic properties. Taiwo et al. investigated the activity of stem bark of A. boonei de wild on human complement and polymorph nuclear leucocytes, Taiwo and Makinde reported on the effect of lyophilized aqueous extracts of A. boonei stem bark on guinea pig ileum and rat stomach strip. Oze et al. also investigated the nephrotoxicity caused by the extract of this plant in guinea pigs and on reproductive functions of methanolic extract of A. boonei in male rats.
According to The Useful Plants of West Tropical Africa, the bark, and the root, are febrifugal and are said in Nigeria to be very effective in the case of ordinary malaria. It reads: “A bark-decoction is also taken in Ghana for malaria and in Cameroun. The bark of an Alstonia sp. is used in India for malaria and chronic diarrhoea. It is said to be inferior to cinchona bark but leaves no after-effects, e.g. no buzzing in the ears. In decoction it is used in Ivory Coast — Upper Volta to cleanse suppurating sores and exposed fractures; in Nigeria for sores and ulcers; on snakebite in Liberia; and for snakebite and arrow-poison in Cameroons (Mildbraed fide 10).
“The bark, leaves and roots are all used to relieve rheumatic pain and other pains. The bark has a widespread use in Ghana to assuage toothache, and the Akan name sindru is a corruption of the words meaning ‘tooth medicine’. In Sierra Leone, a chicken killed by a male child is cooked with pounded bark; the stomach becomes exceedingly bitter and is taken by those, especially women, suffering from intestinal disorders. The boy who killed the chicken must also partake. This treatment is also followed for curing barrenness in women over 30 years of age, and by women with umbilical suppuration — after eating, some pounded bark is bandaged over the navel.
“The bark is taken in macerate in Ivory Coast for jaundice, and sap for cough and sore throat, and externally for some skin-complaints. In Ghana a decoction is given after childbirth to promote expulsion of the afterbirth. The bark has anthelmintic use in Sierra Leone: it may be boiled and the liquor strained and taken, especially for children, or simply left to stand in a bottle of water.Two indolic alkaloids, echitamine and echitamidine, have been determined in the bark, which in concentration appears to vary with location: Ghana 0·38–0·56 per cent, Nigeria 0.15–0.31 per cent, and Cameroons 0·18 per cent, total alkaloids, principally echitamine. This is paralysing to the motor nerves similar to the action of curare. A lactone and triterpenes, amyrine and lupeol, have also been reported.
“The latex is dangerous to the eyes and can cause blindness. It gives an inferior resinous coagulate which has been used to adulterate better rubbers. It has been used as a birdlime. The latex is applied to snake-bite after lancing in Ivory Coast, or it may be taken by draught. The latex is boiled in Nigeria and the concoction is taken for fever, especially in children. In Casamance (Senegal) latex is applied to refractory skin-troubles in children. It is also smeared onto ‘Calabar Swellings’ caused by Filaria infection in Cameroons and the area is bandaged with latex and the crushed bark of Erythrophleum guineense (Leguminosae: Caesalpinioideae) (Mildbraed fide 10). It is considered galactogenic and is given to Baakpe women of the Cameroons Mountain area at childbirth.
“The latex is supposed to be an antidote for Strophanthus poison. The leaves, pulped to a mash, are applied topically in Ivory Coast to reduce oedemas, and leaf-sap is used to cleanse sores in Casamance. The tree has religious association for the Akan races in Ghana as shown by the names meaning ‘Sky-God’s tree.’ This arises from the whorled branches of a young shoot being used to support fetish bowls holding food for spirits at domestic shrines.”