Herbal cocktail for drug-resistant malaria

Can hot infusion from the boiled green leaves of pawpaw combined with leaves of neem tree, lemon grass, guava, and stem bark of pattern wood drunk as one wine glass full three times daily be the elusive treatment for drug-resistant malaria? CHUKWUMA MUANYA writes.

 MOST conventional malaria drugs even the World Health Organisation (WHO)-approved medication of choice, artemisinin, may no longer be able to treat the killer disease. Why? Researchers found malaria samples collected in and around Myanmar contained evidence of resistance to the frontline drug artemisinin.

     The researchers in the study published last week in The Lancet Infectious Diseases warn that if the resistant parasite spreads into neighboring India, it would pose a serious threat to the global control and eradication of malaria.

      Indeed, the warning is a reminder of what happened 50 years ago when malaria resistant to the drug chloroquine emerged in Asia, spread from Myanmar to India and then to the rest of the world, claiming millions of lives in its wake.

       However, Nigerian researchers have developed herbal cures for malaria that can take care of resistant strains. The researchers have produced potent anti-malaria cocktails from local plants, which explain the reported use of both the leaves of these plants together with other plant parts by herbalists for malaria treatment in Nigeria. 

     Indeed, several local plants have been validated for treating drug-resistant malaria. The local plants were identified by two recent but separate studies published in International Journal of Pharmaceutical Research and Bio-science and International Journal of Pharmaceutical Science and Drug Research. 

    The local plants include: Neem tree (Azadirachta indica), Pattern wood (Alstonia boonei); Tropical almond (Terminalia catappa); Pawpaw (Carica papaya); Akuamma plant (Picralima nitida); Pentaclethra macrophylla (African oil bean tree); Phyllanthus niruri (stonebreaker); Euphorbia hirta (asthma herb and eczema drug); Newbouldia laevis (Chieftaincy leaf).

      The researchers from the University of Nigeria, Nsukka, Enugu State, led by J. D. N. Ogbonna of the Drug Delivery Research Unit, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, wrote: “Malaria has continued to cause deaths and ill health on a large scale, especially among the highly vulnerable groups, young children and pregnant women in tropical countries. In Africa, it causes more than one million deaths every year, and in Nigeria, the infection rate has been described as holoendemic, with more than 75 per cent of children aged between five and nine years infected and there is need for scourge. 

     “This need has further been highlighted by the current recommendation of artemisinin (a plant product) based combination therapies. Artemisinin, obtained from Artemisia annua, and quinine, obtained from Cinchona species, are proven instances of compounds derived from plants with anti-malarial potential. 

    “Plant preparations have a very special characteristic that distinguishes them from chemical drugs: a single plant may contain a great number of bioactive phytocompounds and a combination of plants even more. This complexity is one of the most important challenges to phytoscientists attempting to identify a single bioactive phytocompound or chemical group in the enormous universe that comprise single crude extract. Many plant genera were found to be used either as alone or in combination with each other for the treatment of malaria. 

    “Malaria is an infectious disease caused by a parasite transmitted to humans by mosquitoes. Plasmodium falciparum causes malaria with immense public health and economic problems in most developing countries and for many years these problems have been intensified by the emergence and spread of resistance to the currently available antimalarial drugs. 

     “Herbs for malaria work in diverse ways. Some contain chemicals that interact with your immune system to kill the Plasmodium parasite… Vicious cycle of malaria and poverty continues in its most severe form in the developing economies where poorest of poor do not have access to unaffordable costly treatment.

    “Ideally, new drugs for uncomplicated P. falciparum malaria should be efficacious against drug- resistant strains, provide cure within a reasonable time (ideally three days or less) to ensure good compliance, be safe, be suitable for small children and pregnant women, have appropriate formulations for oral use and above all, be affordable. 

    “However, Nigerian researchers have also developed herbal cures for malaria that can take care of resistant strains. They have produced potent anti-malaria cocktails from local plants. This may possibly explain the reported use of both leaves together with other plant parts by herbalists for malaria treatment in Nigeria. According to (Uhegbu et al, 2009) on Comparative Anti-malarial effects of Sulphadoxine/Pyrimethamine (SP) and aqueous leaf extracts of Carica papaya, Magnifera Indica in mice there were consistency with reported anti-malarial activity of these plants. 

     “According to (Oparaocha and Okorie, 2009) aqueous extracts of the stem bark, fruit pericarp, seeds and leaves of Pentaclethra macrophylla (African oil bean tree, ugba in Igbo); the leaves of Phyllanthus niruri (stonebreaker) and the leaves of Euphorbia hirta (asthma herb, ogwu ngwo meaning eczema drug) were tested for anti- plasmodial activity using albino mice. These studies inferred that extracts of these herbs can be used by local communities of South Eastern Nigeria to treat malaria.”

     The study is titled “Evaluation of six herbal plants used in the treatment of malaria in South-Eastern Nigeria: A review.”

    Commonly called stonebreaker, Phyllanthus niruri also known as ‘Chanca piedra’ belongs to the family Euphorbiaceae. Phyllanthus niruri is similar to Phyllanthus amarus, which also belongs to the same family. 

   Euphorbia hirta belongs to the plant family Euphorbiaceae. It is called In Nigeria, asin uloko in Edo, endamyel in Fula-Fulfulde, ba ala in Igbo (Owerri), akun esan in Yoruba.

   Euphorbia hirta is also locally known as ogwu ngwo (eczema drug) in some eastern parts of Nigeria is used locally to arrest bleeding in the event of an injury. Leaves of Euphorbia hirta are used in traditional medicine for the treatments of boils, wounds and control of diarrhoea and dysentery.

Azadirachta indica

    The name is derived from the Persian word azaddhirakt, which means “noble tree”. It is called oguru akam and obisikeosiso in Igbo, Dogo’nyaro in Hausa and aforo oyinbo in Yoruba.

       Method of extraction and preparation of Neem: The tender parts of the branches are cut and the leaves with other parts are washed thoroughly and put inside a pot (metal or clay) after the size must have been reduced with knife. About four litres of water are then added and the content boiled for about 30 minutes. It is then allowed to cool for some time and filtration is done with a muslin cloth. The filtrate which is the drug product is administered orally with a glass cup once three times daily, more water is added to continue extraction if the extracts reduces. 

    The drug extract can sometimes be used as anti-inflammatory, anti-spasmodic and as insecticidal agents. Other medical situations in which Neem can be used are liver ailments, gastric ulcers, constipation, urinary tract conditions, fever, skin problems etc.

     Neem products have been shown to exhibit a wide range of effects that are potentially useful for malaria control and include antifeedancy, ovicidal activity, insect growth regulation and repellency. These effects are frequently attributed to the azadirachtin contents of the products. 

      Neem-based products are relatively safe towards non-target biota, with only minimal risk of direct adverse effects on aquatic macro invertebrates resulting from contamination of water bodies with neem-based insecticides. In addition, the products are less likely to induce resistance due to their multiple modes of action on insects. 

     Research on neem products for the control of arthropods of medical and veterinary importance has been ongoing for some time and various studies have focused on the culicine species Culex tarsalis and Culex quinquefaciatus, besides Aedes aegypti. There have also been studies that assessed the larvicidal potential of neem products on anophelines, notably Anopheles culicifacies, Anopheles arabiensis, Anopheles gambiae and Anopheles stephensi.

Performing your original search, Azadirachta indica and Nigeria, in PubMed will retrieve 42 records.

      According to a study published in the Nigerian Journal of Physiology and Science, recently, a fractionated neem-leaf extract known as IRAB with reported activities against malaria, Human Immuno-deficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS) and cancer has been developed into a drug and currently marketed in Nigeria as IRACAP.

Alstonia boonei

     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.

      Method of extraction and preparation of Alstonia boonei: The fresh barks and leaves are cut with knife, washed thoroughly and put inside a pot containing about two litres of water. The pot content is allowed to boil for 30 minutes and left to cool for 10 minutes after which the content of the pot is filtered using a muslin cloth. The drug filtrate is taken two glassfuls three times daily in feverish conditions to treat malaria. Alstonia boonei also finds usage in the followingailments hypertension, fever, rheumatism, lactation stimulant, parasites,snakebite, arrow poison etc.

      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.

     “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…”

Terminalia catappa

Commonly called Tropical almond or Indian almond. Terminalia catappa is an ornamental tropical tree belonging to the family Combretaceae. It is native to Southeast Asia.

     Method of extraction and preparation Terminalia catappa. The leaves of Terminalia catappa contain many hydrolysable tannins, such as punicalagin, punicalin, terflavins, A and B tergallagin, tercatain, chebulagic acid, geraniin, granatin B, and corilagin, but no caffeine. The leaves are combined with other components of the plants and boiled. The contents are allowed inside the pot and glass cups are used to scoop the extract and administered orally once two times daily for malaria therapy. The leaves have many medicinal uses including diaphoretic, anti-indigestion and anti- dysentery. 

    An infusion of the young leaves or scraped bark is occasionally taken as a portion for treating mouth infections in Tonga and Samoa and is used in the Cook Islands to bathe fractures. Young leaves are used in the Philippines to cure headache and colic. The bark is used as an astringent in dysentery and thrush.

    According to Wikipedia, the leaves contain several flavonoids (such as kaempferol or quercetin), several tannins (such as punicalin, punicalagin or tercatin), saponines and phytosterols. Due to this chemical richness, the leaves (and the bark) are used in different herbal medicines for various purposes. For instance in Taiwan, fallen leaves are used as an herb to treat liver diseases. In Suriname, an herbal tea made from the leaves is prescribed against dysentery and diarrhea. The leaves may contain agents for prevention of cancers (although they have no demonstrated anticarcinogenic properties) and antioxidants, as well as anticlastogenic characteristics. Extracts of T. catappa have shown activity against Plasmodium falciparum chloroquine (CQ)-resistant (FcB1) and CQ-sensitive (HB3) strains.

Carica papaya

      Commonly called pawpaw or papaya, Carica papaya belongs to the plant family Caricaceae. In Nigeria, it is also known by different local names depending on the tribe. For example, it is known as Ibepe in Yoruba, gwanda in Hausa, ojo and okwere in Igbo, and etihi- mbakara in Efik.

     The ripe fruit is edible and is usually eaten raw, without the skin or seeds. The unripe green fruit (which is a rich source of vitamin A) can be eaten cooked, usually in curries, salads and stews as used in Thai cuisine.

       Different parts of the plant are attributed with different medicinal values. For instance, in African folklore medicine, the hot infusion from the boiled green leaves of papaya combined with leaves of Azadirachta indica, Cymbopogon citratus (lemon grass), Psidium guajava (guava) and stem bark of Alstonia boonei is drunk as one wine glass full three times daily in the treatment of malaria.

     Method of extraction and preparation of Carica papaya: The leaves are mixed with guava leaves, lime leaves and lemon grass. They are then put inside a pot and the mixture is boiled though the leaves do not have to soften so much. On noticing the coffee colour of the mixture it is assumed that the extraction is complete and boiling is stop instantly. From the content in the pot two glass cups are taken orally twice daily without filtration of the content to treat malaria. Carica papaya can still be used in the following sickness hypertension, digestive problems, stomach pain, diuretic, malaria, parasites etc.

    The extracted product apart from being used in malaria therapy is used to treat amoebicide, antihelmintics and as a carminative in our local villages and towns. 

     A 2013 study published in Journal of Medicine and Medical Sciences reads: “… The fresh leaves Carica papaya is also efficacious in the treatment of gonorrhea, syphilis and amoebic dysentery. The whitish sap of the unripe fruit is a potent abortificant, anti-helminthic for roundworms, stomach disorders and enlargement of liver and spleen. The seeds are also effective as a vermifuge and are very useful in the treatment of hypertension, diabetes mellitus and hypercholesterolemia.

      “Results from investigations on the biological activities of Carica papaya parts, extracts and isolated compounds showed that the latex and root extracts inhibited Candida albicans while extracts of pulp and seeds showed bacteriostatic properties against Staphylococcus aureus, Escherichia coli, Salmonella typhi, Bacillus subtilis, and Entamoeba histolytica, in vitro. Its root aqueous extract has equally been shown to have purgatory effect.

    “Papaya (Carica papaya) is a major fruit crop in many tropical parts of the world. It has been ranked first amongst 38 common fruits based on its accordance to the United States Recommended Daily Allowance for many vitamins, and consumption of papaya has been recommended for preventing vitamin A deficiency, which causes childhood blindness in many tropical and subtropical countries.

     “The fruits, leaves, seeds and latex are used medicinally. The folklore medicinal use of Carica papaya is as a digestive agent. The latex from the trunk of the tree is also applied externally to enhance ‘quick’ healing of wounds, ulcers, boils and warts. The seed is used to expel worm, the flower may be taken in an infusion to induce menstruation. Annonaceous acetogenins derived from the extracts of the twigs of the Carica papaya tree may be good chemotherapeutic agents for cancer as these compounds inhibit enzymes necessary for metabolism in tumor cells.”

Picralima nitida

     Commonly called Akuamma plant, Picralima nitida belongs to the plant family Apocynaceae. It is called Osu-igwe in Igbo and Erin in Yoruba. Many herbalists have claimed to use the leaves, seed or stembark as treatment for various fevers, hypertension, jaundice, gastro-intestinal disorders and for malaria. The seed, stem and roots have been reported to be effective as a cough suppressant anodyne, as well as an aphrodisiac and hypoglycaemic agent in treatment of diabetes. 

     Literature survey on scientific journals, books as well as electronic sources have shown the isolation of alkaloids, tannins, polyphenols and steroids from different parts of the plant, pharmacological studies revealed that the extract or isolated compounds from this species posses analgesic, anti-inflammatory, hypoglyceamic, hypotensive, antiplasmodial, antimicrobial, antiulcer and antitumorigenic activities. 

    Results from various scientific investigations to date have revealed the potential of the extract from the plant or isolated compounds for use in the treatment and prevention of various kinds of human diseases

    Method of extraction and preparation of Picralima nitida. The exudates of stems are collected and the fruit content is scooped out and the empty shell filled with palm wine. The wine will soak the shell and absorbed the bitter principle inside the shell. The mixture formed after absorption is taken three times daily with a glassful of it to treat malaria. Apart from malaria, it can also be used for hypertension, stomach pain, liver problems, pneumonia, sleeping sickness.

 Newbouldia laevis

     Commonly called chieftaincy leaf, Newbouldia laevis belongs to the plant family Bignoniaceae. To the Igbos it is ogirisi, the Tivs call it konkor and obat in Efik, nsor in Boyki, ikhimwin in Edo, àdùrúkù in Hausa, itömö in Ibibio, agishi in Jukun, ashishan in Tiv, and akoko in Yoruba. 

    Method of extraction and preparation: For stomachache and malaria; the leaves are washed and given to the patient to chew. The patient is later given a glassful of water to drink to wash down the leaves.

     For snakebite or scorpion bite; the leaves are plucked and squeezed to extract the fluid content. The leaves are then used to scrub on the bite site (snake or scorpion) to relieve the pain.

      Apart from its application as a plant whose leaves are used to mark the conferment of traditional titles on individuals in many communities, the plant has a wide range of medicinal applications in ethnomedicines. It is used in the treatment of malaria fever, constipation coughs, toothache, sexually transmitted diseases and breast cancer. 

   Some of the ethnomedicinal applications have been scientifically verified. While Usman and Osuji, (2007) reported the remarkable antimicrobial potentials of the leaf methanol extract Chukwujeku et al, (2005) investigated the anti-inflammatory and the antimalarial activities of the root extracts. 

   The phytochemical constituents of the plant’s stem bark have been reported to include anthracene derivatives like the uranonaphthoquinones and Newbouldiaquinone. In addition, Germann et al (2006) revealed the presence of newbouldioside A-C, phenylethanoid glycosides in the stem bark while flavonoids, and tannins are found in the leaf Usman and Osuji, (2007).

     According to The Useful Plants of West Tropical Africa by H. M. Burkill, the decoction of the bark is given to children in Ivory Coast and Nigeria for epilepsy and convulsions. The bark is used in Ghana as a stomachic and in the form of an enema for constipation and piles; the bark is also said to cure septic wounds. 

         The bark is used in Guinea to treat snake-bite, while in Ghana the chewed-up leaves are applied to the wound which is then sucked to draw out the venom. Analgesic properties are said to reside in the bark. One or two sniffs or a snuff made of the sun-dried bark ground up with palm salt (K2CO3) or ‘sel de Taoudenit’ and the fruits of Piper guineense Schum. & Thonn. (Piperaceae) are taken for headache, sinusitis, head-colds, etc. in Ivory Coast, and will dispel the most obstinate migraine. Perhaps similar use as snuff accounts for the Krio name ‘snuff-leaf in Sierra Leone. In Gabon bark heated in a little boiling water is patted on the head for headache. 

     Bark pulped up to a paste is used in Casamance (Senegal) on rheumatism, especially painful arthritis in the knee. In some cases a plaster is applied after massage, and in refactory cases where walking has become impossible various parts of Trichilia prieuriana (Meliaceae) are added to an aqeous infusion of N. laevis roots for internal and external use.   

     A bark-decoction is taken in Nigeria, and Togo for dysentery. The outer bark is decocted with chilis in Ghana and the liquor drunk for chest-pain and the inner soft bark is put into the ear for earache. In Gabon a preparation is used in lotion for headache and in a gargle for toothache. A decoction of stem and root barks was in the past used with some success in Sierra Leone for acute malaria with splenic enlargement, by application of the crushed leaves with fruits of Xylopia aethiopica in poultice over the spleen, for dysenetry and post-partum and other forms of passive bleeding.    

      Bark boiled in water or palm-wine is commonly used in Congo for cough and diarrhoea. Bark-preparations are also considered healing. In Ghana they are applied to sore feet and septic scores, and as a poultice to aching limbs. In Ivory Coast the bark is used to make washes and hip-baths for chancres, and the liquid obtained by beating the bark in a little water upon a copper coin is used to wash the sore. In Casamance (Senegal) preparations are topically applied in dracontiasis and snake-bite, and to abscesses and ulcers. It is used on breast-tumour in Ghana, and in Nigeria the bark and roots grounded up and mixed with oil and human faeces have been applied as an ointment on wounds. 

      The plant (part not stated, but probably the bark) is used in Upper Guinea sometimes against leprosy, and then is said to be some benefit. In Congo the chest is rubbed with sap obtained by pounding the bark with leaves of Kalanchoe sp. (Crassulaceae) for pulmonary affections. As a veterinary medicine, bark is fed to horses in Senegal to improve their appetite. 

     The roots and leaves are often used together. They are a familiar remedy for scrotal elephantiasis, or for any form of orchitis, a decoction being drunk or the materials pounded up together and applied hot. They are also credited with aphrodisiac properties. 

     In Nigeria they are boiled together for administration as a febrifuge. The roots alone are pounded up with Lophira (Ochnaceae) in Senegal for massaging onto areas of oedema arising through dietary deficiency, and a macerate or decoction of the roots is taken by mouth as a vermifuge for roundworm in Senegal, and in Guinea, and to treat hernia in Senegal and syphilis in The Gambia. The treatment is purgative and is regarded as more or less toxic. 

     The roots are used in Senegal and in The Gambia against dysentery and for rheumatic swellings. They are also used in Nigeria as a roundworm vermifuge and stomachic, and for migraine and earache. In Liberia root-scrapings mixed with chili are put into a carious tooth. A plaster is made from the roots for treating bad feet in The Gambia. 

    Stem-bark is used by herbalists in Nigeria for treating skin-infections. Examinations of boiled water extracts showed some activity against Gram +ve Sarcina lutea, but no action against Staphylococcus aureus and Mycobacerium phlei, nor against Gram –ve organisms; nor was there any anti-fungal activity.

      The leaves are used in decoction in Nigeria as an eye-wash in conjunctivitis, ophthalmia etc; they are cooked in palm-oil soup in Ghana and taken by pregnant women in order to effect easy delivery, and after parturition to promote a rich milk supply. Belief in the facilitating of childbirth pertains also in Ivory Coast. A decoction of the leaves with those of Psidium guajava (Myrtaceae) is taken in Ivory Coast for diarrhoea and dysentery. In Sierra Leone leaf-ash mixed with salt is taken as a remedy for pain over the heart. Leaves are used in Sierra Leone as a wrapper to hold tobacco snuff. It is said that stains on the hands can be removed by the leaves.

     Tannins are present in the bark of Nigerian material and in plants from Guinea-Bissau and Congo. Screening of the roots for antimalarial activity has shown no action against avian malaria.