NIGERIAN researchers have made progress in developing herbal cures for Human Immuno-deficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS), malaria and tuberculosis (TB). CHUKWUMA MUANYA reports.
They are the top adult killer diseases in the developing world today. The United Nations, Global Funds for AIDS, TB, and Malaria and the World Health Organisation (WHO) have declared war against this triple menace.
Scientists, WHO and Health ministries of many countries in the developing world through research agencies are urgently searching for new, alternative but herbal remedies for AIDS, TB and malaria.
The quest is following the failure of conventional drugs for these diseases and the genuine fears that they may develop resistance to current drugs.
In Nigeria, the National institute for Pharmaceutical Research and Development (NIPRD), Abuja, and the Nigeria Natural Medicine Development Agency (NNMDA), Lagos, are blazing the trial. They have made progress in developing herbal cures for AIDS, malaria and TB.
Also, a WHO-led effort to support drug discovery in Africa based around traditional herbal remedies is now in its fourth year. It involves an ambitious effort to foster pan-African hubs and laboratories for in vitro (outside a living environment) and in vivo (inside a living environment) natural product screening, which can serve scientists across the continent.
Hopes are high that over the next few years, at least one viable lead compound might be identified that will not only cure HIV/AIDS, malaria and TB and the attendant drug resistance associated with conventional drugs, but will be accessible and cheap.
Director General NNMDA, Dr. Tamuno F. Okujagu, told The Guardian: " For malaria, apart from the herbal combination therapy we are looking at, we have so far screened over 20 plants, looking at those that have potentials. We are also screening plants for diabetes, TB and hypertension. The screenings are on-going; they are part of the critical projects we have going on now. But for malaria, we think it is one of the major developmental challenges of Nigeria and sub-Saharan Africa and that is one of our priorities.
"Already, we have an observational study going on for HIV/AIDS and we are also looking at a number of issues there. Mainly on the issue of immune boosters and antibacterial and antiviral plants and how they can be used in combination to achieve some kind of results.
"A number of plants are being screened to see which ones have the properties that can manage TB. If you note, I am sure there are some people with TB, who have been treated or manage with some kind of herbal therapy. We need to find those therapies and we need to know what is in them and need to take of note and do them better."
A study on preliminary evaluation of a local phytomedicine for the management of HIV/AIDS by a team of researchers from NIPRD published in the Newsletter of the International Conference on AIDS investigated the potential value of a herbal product used locally for the treatment of AIDS patients.
The researchers include; Wambebe C, Gamaniel K, Ibrahim K, Abimiku A, Sule U, and Eyo V. They said the drugs currently in use against HIV/AIDS have cumbersome dosage regimen, unbearable and potentially fatal adverse effects, and are generally unaffordable hence the need for cheaper and less toxic alternatives.
The researchers studied the freeze-dried extract of the crude medicinal sample. Laboratory animals, as well as, clinical isolates of Mycobacterium tuberculosis, Candida albicans, Bacillus subtilis, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Mycobacterium smegmatis were used for the experiments. Acute toxicity (LD50) was determined. The minimum inhibitory concentration and minimum bactericidal concentration were determined. Immuno-active studies were carried out using the passive cutaneous anaphylaxis (PCA) model in rats.
The results indicated that no remarkable adverse reaction was recorded in laboratory animals within 24 hours. The preliminary data suggest immuno-stimulant activity of the extract. The sample caused a dose dependent relaxation of both the isolated guinea pig ileum, and the rabbit jejunum. No anti-TB activity was recorded, but significant inhibitory activity was noticed against Candida albicans, Esherichia coli and Pseudomonas aeruginosa.
The researchers wrote, " the product appeared to be safe and may be useful against some opportunistic infections. The relaxant effect on the guinea pig ileum and rabbit jejunum corroborates the use of the product since this could be beneficial in the treatment of profuse diarrhoea, which is frequently noticed in AIDS patients."
They concluded that with the discovery, cheaper and safer drugs for the management of HIV/AIDS could be developed.
Indeed, NIPRD have developed formulations from local plant extracts, which have been studied in the Institute. They include: A solid dosage form of NIPRISAN, a preparation for the Management of Sickle Cell disease; A solid dosage form of CONAVIL, a preparation for use in the supportive Management of HIV/AIDS; A solid dosage form of NIPRD AM-1, a preparation for the treatment of uncomplicated malaria; A semi solid topical preparation of NIPRISAN for the treatment of fungal infections; and A solid dosage form of a plant extract for the management of peptic ulcer.
NIPRD's Deputy Director and Head of Department of Microbiology, Human Virology and Biotechnology, Dr. Kolo Ibrahim said that the Institute is committed to the research and development of anti microbial agents from natural sources and research and development of herbal remedies for priority diseases namely HIV/AIDS, Malaria and tuberculosis.
Ibrahim said NIPRD takes care of the validation of anti - HIV/AIDS claims of recipes received from traditional medical practitioners and screening of Nigerian plants for anti-tuberculosis activity, funded by the National Institutes of Health (NIH).
Until now, Nigeria has developed phytomedicines for ulcers, anemia, contraception, malaria and HIV, and it now holds patents for some of these medicines in several countries.
Director General of NIPRD), Dr. Charles Wambebe, at the WHO Forum on Traditional Medicine in Health Systems, Zimbabwe, Harare, February 14-18, 2000, gave a fascinating presentation about the development of two phytomedicines.
The presentation was published in Journal of Alternative and Complementary Medicine.
Both were developed from herbal medicines obtained from local traditional healers. The NIPRD followed a procedure in which the traditional healers and their patients sign consent forms, allowing study of the phtomedicine and the effects on patients.
In phase 1 placebo-assisted clinical trails, patients were given the experimental phytomedicines for both sickle cell anemia and for HIV. After three months, patients in the experimental group were found to be improving. The clinical trials are continuing. The NIPRD is also targeting malaria, and started a pilot clinical trial of a new antimalarial phytomedicine in July 2000.
The HIV/AIDS phytomedicine is called Dopravil. From preliminary anecdotal and experimental evidence, the new compound looked promising.
Wambebe said: "But since research results will no doubt be published, I will confine my comments to the NIPRD's plan for recognising the intellectual property rights of traditional healers by means of a scheme for sharing any future royalties from a phytomedicine that becomes a profitable drug (or patentable comound). For most of the history of drug development in which initial drug discovery leads came from indigenous healers, both the healers and their communities received no benefit."
According to a study published in Antimicrobial Agents and Chemotherapy, titled "Inhibition of Mycobacteria by Garlic Extract (Allium sativum)" by Edward C. Delaha and Vincent F. Garaguis of the Microbiology Division, Department of Clinical Laboratories, and Infectious Disease Service, Department of Medicine,
Georgetown University Hospital, Washington, United States, 30 strains of mycobacteria (the organism that causes tuberculosis), consisting of 17 species, were inhibited by various concentrations of garlic extract. The concentration required ranged from a low of 1.34 mg/ml to a high of 3.35 mg/ml of media.
Before now, the inhibitory effect of garlic on mycobacteria has been reported only on rare occasions. Around the turn of the century, W. C. Minchin, head of the Tuberculosis Ward at a Dublin Hospital, wrote that garlic had a remarkable cure rate for tuberculosis. It was used as an inhalant, taken internally, and applied as a compress and as an ointment.
McDuffie, at approximately the same time in New York City, compared garlic with 55 other treatments for tuberculosis and concluded that it was the most effective.
In the only previous study to quantitatively determine the concentration of garlic extract that inhibited Mycobacterium tuberculosis, using only one strain of M. tuberculosis, found that 2 mg/ml was required to inhibit that particular strain. To confirm their study and to determine the inhibitory concentration of garlic for several strains of M. tuberculosis as well as for 16 other species of mycobacteria, the Antimicrobial Agents and Chemotherapy study was undertaken.
The inhibitory effect of garlic on M. tuberculosis has been mentioned in clinical reports for nearly 100 years; however, the only previous laboratory evaluation was performed by for a single strain of M. tuberculosis.
The researchers wrote " in this study we were able to confirm their quantitative determination of the concentration required to inhibit M. tuberculosis and to establish evidence of the inhibitory nature of garlic extract on 16 other species of mycobacteria.
"Of the six strains of M. tuberculosis tested, four required 1.34 mg/ml, one required 2 mg/ml, and one required 2.68 mglml for inhibition. These data suggest that there is only a slight variation in the susceptibility of the strains to allicin. Three strains of the commonly isolated photochromogenic pathogen M. kansasii required a mean inhibitory concentration of 2.45 mg/ml. M. fortuitum, M. flavescens, M. intracellulare, M. simiae, and M. szulgai required the most extract, 3.35 mg/ml. Overall, the concentration required to inhibit the 30 strains tested ranged from 1.34 to 3.35 mg/ml.
" Whether garlic extract has any future in treating human mycobacterial infections remains to be evaluated. If the in vitro studies of the inhibitory power of garlic extract against mycobacteria can be interpolated, it may be surmised that very high levels in serum would have to be achieved.
"These high levels could be toxic to the -SH groups of the animal or human being treated. Further studies in animals are indicated to determine achievable safe blood levels and overall toxicity. It is conceivable that smaller amounts or garlic extract along with other standard antituberculosis drugs may act synergistically against mycobacterial infections."
However, local researchers have made huge progress on herbal cures for malaria. One of such herbs used to treat malaria that efforts are currently on to study its safety limits is Enatia chlorantha, a herb that bears different local names in Nigeria. The stem bark of this plant also known as African yellow wood among the Yoruba speaking community is called "Iyani" or "Awopa" while in Benin it is called "Evenbavbogo"
In Nigeria, the bark extract are used widely to treat malaria fever, high body temperature, wounds, kick start labour in pregnant women and as a naturally occurring antibiotics.
The plant is also used traditionally to treat jaundice, tuberculosis and leprous spots and many researchers including Dr. E. A Agbaje from the department of Pharmacology, College of Medicine, University of Lagos in the journal West African Journal of Pharmacology and Drug Research of year 2005, have even confirmed that its aqueous extract is effective in the treatment of conditions like ulcer.
Nigerian researchers have shown that the fruit extract of Tetrapleura tetraptera possesses significant anti-malarial, analgesic and anticonvulsant activities.
Tetrapleura tetraptera belongs to the family Fabaceae (formerly Leguminosae:Mimosoideae). To the French it is esehese a grandes feuilles. In Nigeria it is ebuk in Bokyi; esegheseghe (rattling), ighimiakhie or ikhememi in Edo; edeminang (four backs) in Efik; manto in Ejagham; ekpankpan or ekuk in Ejagham-Etung; ighirehimi in Esan; dawo in Hausa; Uyayak in Ibibio; ashobo, ashosho, oshogisha (Arochukwu), ora-ora (Awka), osshosha (Bende), osakirisa (Owerri) in Igbo; apapa in Ijo-izon; idisain in izon; yurem in Nkem; arida, arizan, ayida or ikoho in Nupe; sekok-mpap in Nyanga; mangongon in Yamba; imiminje in Yekhee; and aidan (Ife) or aridan (meaning cast no spell) in Yoruba.
The fruit extract of Tetrapleura tetraptera has been shown to possess antiplasmodial (active against malaria parasite) activity, which may have contributed to the immune status of the Nigerians against malaria in addition to its nutritive value.
Researchers at the Pharmacology and Toxicology Department, Faculty of Pharmacy, University of Uyo have confirmed the antimalaria activity of ethanolic extract of Tetrapleura tetraptera fruit. The researchers include: Okokon J. E., Udokpoh A. E., Antia B.S.
The in vivo (inside a living environment) antiplasmodial activity of the ethanol fruit extract of Tetrapleura tetraptera was evaluated in Plasmodium berghei (one of the many species of malaria parasites that infect mammals other than humans) infected mice.
Tetrapleura tetraptera (300-900 mg/kg day) exhibited significant blood schizonticidal activity both in four-day early infection test and in established infection with a considerable mean survival time comparable to that of the standard drug, chloroquine, 5 mg/kg day.
According to a study titled Formulation of an effective mosquito-repellent topical product from lemon grass oil published recently by the Department of Pharmaceutics, Obafemi Awolowo University, Ile-Ife, Nigeria, extracts of lemon grass can not only bring relief in malaria fever, but can repel mosquitoes.
The team of researchers: Oyedele A.O, Gbolade A.A, Sosan M.B, Adewoyin F.B, Soyelu O.L, and Orafidiya O.O evaluated ointment and cream formulations of lemon grass oil in different classes of base and the oil in liquid paraffin solution for mosquito repelling property in a topical application.
Mosquito repelling property was tested by determining the bite-deterrence of product samples applied on an experimental bird's skin against a two-day starved culture of Aedes aegyptica mosquitoes. The one per cent v/v solution and 15 per cent v/w cream and ointment preparations of the oil exhibited not more than 50 per cent repelling lasting two to three hours, which may be attributed to citral, a major oil constituent. According to the authors, this activity was comparable to that of a commercial mosquito repellent.
A study by Gordian C. Obute of the Department of Plant Science and Biotechnology, University of Port Harcourt has unveiled some 35 medicinal plants scattered in 23 plant families, with reported medicinal importance to the people of South-eastern Nigeria.
The study indicates that drinking or bathing with leaf decoction or infusion of Neem or Dogoyaro (Azadirachta indica) of the plant family Meliaceae is a remedy for chicken pox and small pox, boiling leaves with lemon grass treats malaria, used as a vermifuge, remedy for ulcers and wounds.
According to the study, unripe fruit of papaya or pawpaw (Carica papaya), which belongs to the plant family Caricaceae when mixed with garlic and fermented for three days is used as a diuretic. Chewing a handful of seeds of pawpaw, in the morning and evening and add decoction of unripe papaw with unripe pineapple, lime, 10cm long sugar cane piece, six bags of Lipton tea in four litres of water has anti-malarial effects.
The study also indicated that boiling of Mango leaves, Mangifera indica (Anarcadiaceae) in water and drinking the resultant solution is a cure for malaria; Bark is soaked for 24 hours and the water extract is used, along with bathing with this three times a day, to treat typhoid fever.
The stem of Broom weed (udo or nsi inyinya in Ibo is used to treat malaria. It is also called Sida acuta (Malvaceae).
Elsewhere, a working document prepared for the 21st session of the African Advisory Committee for Health Research and Development (AACHRD) on enhancing research into traditional medicine in the African region reported progress made in 2002 by WHO-sponsored pilot controlled clinical trials involving a small number of patients of up to 20, conducted by some institutions in Ghana, Kenya and Nigeria, using a specific protocol.
In these pilot clinical trials, the study group was administered traditional medicines and the control group was given either chloroquine or Fansidar.
The results show that some traditional medicines are able to clear parasites within seven days of treatment in most of the patients in the study group, without any observable side effects. The investigations are still continuing.
Seven herbal preparations for the treatment of various conditions, including malaria, have been included in the National Essential Drugs List of Mali. In Madagascar the work of the "Institut Malgache pour la Recherche AppliquZe (IMRA)" on malaria has resulted in a discovery of a new drug, which is effective against chloroquine-resistant strains.
However, more research is required to confirm this finding. Countries that are conducting research on evaluation of herbal preparations for the management of HIV/AIDS include: Benin, Burkina Faso, DRC, Ghana, C�te d'Ivoire, Kenya, Mali, Nigeria, South Africa, Tanzania, Togo, Uganda and Zimbabwe.
In all these countries, except Nigeria, Uganda and South Africa, which have conducted pilot clinical trials, only observational studies have been carried out due to ethical considerations and financial constraints.
Preliminary results show that some herbal preparations reduce viral load. In addition, improvements have been noted in the quality of life and clinical conditions of patients treated with the locally produced medicines. Blood tests to monitor the level of immunity (CD4 and CD8 counts) of patients, all of whom are being treated exclusively with traditional medicines, has shown a marked increase in blood cell counts. In some countries such as Burkina Faso, a weight gain of up to 20 kilograms has been noted in some patients within four months of treatment.
In Tanzania, Warburgia species are used effectively for the treatment of people living with HIV/AIDS (PLWA).
WHO is supporting ethnomedical studies conducted by institutions in Burkina Faso and Zimbabwe where, apart from baseline CD4/CD8 (markers for the immune system) and viral load values measured at the inception of the study and re-assessed every three months, liver and kidney function tests are being undertaken, using specific protocols.
A local pharmaceutical firm in South Africa has standardised into tablets a herbal preparation, Sunderlandia that is used as a tonic for diseases associated with significant loss of body mass. NIPRD in Nigeria has reported two of the many herbal preparations that Traditional Health Practitioners (THPs) claim to be effective for the management of HIV/AIDS: Dopravil and Conavil on which phase II clinical trials are being conducted.
In Tanzania, Uganda and Zimbabwe it has been claimed that some local medicinal plants are being used effectively for treating fungal infections associated with HIV/AIDS. In Uganda, conventional health practitioners and THPs have been working together since 1992 under the auspices of an Non Governmental Organisation (NGO), Traditional and Modern Health Practitioners Together against AIDS (THETA), to conduct research on medicines potentially useful for combating HIV-related illnesses. Comparing subjects treated with herbal medicines with controls using acyclovir, both groups were found to experience similar rates of resolution of herpes zoster.
The investigators reported that the traditional medicine group had less super-infection, showed less keloid formation and pain due to herpes zoster reduced significantly faster in the group on the herbal medicine compared to those patients on acyclovir.
Results of ethnomedical studies on herbal medicines for treatment of HIV/AIDS, malaria, and sickle cell anaemia are showing that they contain pharmacologically active ingredients. Further research is being undertaken. WHO is providing support is being provided to countries for evaluation of safety, efficacy and quality of these herbal medicines. These countries include but are not limited to, Burkina Faso, C�te d'Ivoire, Ghana, Kenya, Mali, Nigeria, and Zimbabwe.
