The search for better antimalarial 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 weere, 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-Ota, 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.
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
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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.”
