Medicinal plants used in the treatment of sickle cell disease in Western Africa Journal: Journal of Ethnopharmacology Classification: Nutrition and blood

Keywords: Traditional medicine Africa; Medicinal plants; Ethnobotany; sickle cell disease

Manouk Snijders

Abstract

Sickle cell disease is a serious problem in Africa where the required medication is often not available or

too expensive for local Africans. Other possibilities have to be investigated, like traditional medication in

the form of medicinal plants to control the symptoms of the disease. By screening scientific articles, a big

table in Excel was made, containing 93 species which all have a potential effect against sickle cell disease.

Cajanus cajan, Carica papaya, Piper guineense, Pterocarpus osun, Sorghum bicolor, Syzygium

aromaticum, Zanthoxylum zanthoxyloides, Justicia secunda, Moringa oleifera and Vinga unguiculata

seem to be the most promising species for treatment. To solve the problem of unaffordable medication,

a closer look should be taken to the common food crops in the table which have a possible effect against

sickle cell disease.

Introduction

Sickle cell disease (SCD), also known as drepanocytosis, is a genetic blood disorder in which red blood

cells form an abnormal sickle or crescent shape. This genetic disease is due to a mutation in the β-globin

gene in which the 17th nucleotide is changed from thymine to adenine and the sixth amino acid in the β-

globin chain of hemoglobin whereby glutamic acid, a polar amino acid, is replaced by valine, a non-polar

amino acid. This mutation decreases the affinity of hemoglobin for oxygen. At low oxygen tension the

mutant hemoglobin, called hemoglobin S, polymerizes inside the red blood cells leading to a severe

decrease in the red cell deformability. Polymerization and precipitation of hemoglobin S within the red

blood cells cause the change of their shape from their normal disc-like form into one resembling a sickle

(Mehanna, 2001; Bender, 1993; Rees, 2010). In Figure 1, part A shows normal red blood cells flowing

freely in a blood vessel. The inset image shows a cross-section of a normal red blood cell with normal

hemoglobin. Part B shows abnormal, sickled red blood cells blocking blood flow in a blood vessel. The

inset image shows a cross-section of a sickle cell with abnormal hemoglobin forming abnormal strands.

(http://www.nhlbi.nih.gov/health/health-topics/topics/sca/)

Figure 1. Normal and sickled red blood cells.

http://www.nhlbi.nih.gov/health/health-topics/topics/sca/

The symptoms which are caused by the sickle shaped cells are due to a shortage of good functioning

blood cells, which causes anemia, blood clotting and blockage of blood vessels. They vary from fatigue,

to dizziness and headaches, during a mild sickle cell crisis. A drastic sickle cell crisis is an acute episode of

severe pain. These crises occur when sickled red blood cells block the blood flow to the limbs and organs,

which causes the pain and eventually irreversible organ damage (Steinberg, 1999; Bender, 1993).

SCD cannot be cured, so the goal of treatment is to manage and control symptoms, and to limit the

number of crises (www.nhlbi.nih.gov). Patients with SCD need continuous treatment, even when they

are not experiencing a painful crisis. The treatment includes pain medicines, fluids for hydration, blood

transfusion to replace the sickled cells, multiple vaccines and antibiotics. The last two are necessary

because of acute splenic sequestration, which occurs mostly in young patients. Sickle cells clump inside

the spleen, which then becomes enlarged and cannot function properly anymore. This makes the

patients more viable for infections and needy of the vaccines and antibiotics (Emond et al., 1985). In a

crisis situation, multiple operations may be necessary for the transplantation of damaged organs. Also a

bone marrow transplant can be performed, where the bone marrow stem cells are replaced by those of

a donor and the newly made red blood will not form into a sickled shape

(http://www.hematologienederland.nl/sikkelcelziekte).

The problem

Sickle cell disease is prevalent in tropical Africa. In Northern and Southern Africa, 1-2% of the population

is a carrier of the disease, a heterozygote. In countries such as Congo, Gabon, Benin, Ghana and Nigeria

this percentage reaches up to 20-30%. The geographic distribution of the sickle cell trait is similar to that

of malaria. This is because heterozygotes actually have an advantage, above people without SCD, as they

are protected against the severe form of malaria. Consequence is that people who are heterozygous

reach maturity more often than those who are not. In countries, where the percentage of carriers is

higher than 20%, about 2% of the population is born with SCD, the homozygotes

(http://www.afro.who.int).

The required medication to treat SCD is often not readily available to most rural Africans, especially in

the poorest countries. They cannot afford the available treatments, as they always need continuous

medication, because SCD cannot be cured, only controlled. In Congo for example, where the average

daily wage is less than 1 US dollar, people cannot afford the cheapest available haemoglobin S test,

which is about 2.5 US dollars (Tshilolo et al., 2009). Buying this test means they cannot eat for one or

probably more days, and the treatments are not even included yet. All these factors make SCD a large

problem in Africa which should be taken seriously.

Because of the expensive tests, medication and treatments, rural Africans often rely on traditional

medicine to treat this disease, which comes in the form of plant extracts. It is not clear though, which

plant species actually have an positive effect on the sickled cells or the symptoms of SCD and may

function as a treatment for the disease. Experiments have been done on several African plant species to

evaluate their effect against SCD, but no clear overview exists about which species have been tested and

actually have a proven effect.

Aim of the research

The aim of this research is to review which plant species are being used in Africa for the treatment of

SCD, and which of those are promising species to effectively treat this disease. This is very important to

determine, as African people who suffer from SCD may benefit greatly from further testing of these

species. Using effective medicinal plants can be an affordable way for them to treat the symptoms of

SCD and cope with the disease.

Main- and sub research questions

Which plants are used to treat sickle cell anemia in Western Africa?

1. Have these plants been studied pharmacologically for their potential to treat sickle cell disease

related ailments?

2. Which plants have a potential to reduce sickle cell anemia related health problems?

3. How do Africans view the cause and treatment of sickle cell disease?

Method The first step of this research was to search for scientific articles in Google scholar (http://scholar.google.nl/) and Pubmed (http://www.ncbi.nlm.nih.gov/pubmed) about the treatment of sickle cell disease in Africa by plants, and make a clear summary of the results described in these papers. I used the search terms ‘drepanocytose’ and ‘sickle cell’ in combination with the terms ‘disease’, ‘anemia’, ‘Africa’, ‘plants’, ‘herbs’, ‘traditional medicine’, ‘medicinal plants’, ‘anti-sickling’ and ‘anthocyanins’. In order to do this I made an Excel table, containing the collected plant species, family, countries where the species was used in to treat SCD, whether the species had an anti-sickling effect of the red blood cells according to the article, if the anti-sickling or other mentioned effects of the species were proven by means of an in vivo or in vitro test and the active principle in the plant which according to authors, was responsible for the anti-sickling effect. Since many Africans think the colour of the plant affects its effectiveness, they believe that red plant medicines will cure red blood (Cocks et al., 2002). Therefore, I noted whether any part of the plant (roots, stem, leaves, fruit, flowers) had a red, pink or purple colour. This information was acquired from literature or by typing in the species in www.google.com and then clicking ‘Images’, or from images from www.wikipedia.com. Species names were updated by using The Plant List (www.theplantlist.org). I also collected information from unpublished plant use databases from Ghana by postdoc researcher Tinde van Andel, from Benin and Gabon by PhD Candidate Alexandra Towns and from Julie-Anne Borm. Julie-Anne has been a project leader of the Association of Cooperating Parent and Patient Organizations (‘Vereniging van Samenwerkende Ouder- en Patiëntenorganisaties’, VSOP) in the Netherlands. When I listed a species from these databases, I mentioned it in the references as ‘Unpublished’, together with the name of the person of my source. I retrieved all the information in the excel table from the articles, except the tabs ‘Family’, ‘Genus and Species THEPLANTLIST.ORG’ and ‘Red colour’. I got the information of the first two tabs from www.theplantlist.org.

I held an interview with Julie-Anne Borm, who is knowledgeable on SCD and who could tell me her field

experiences about African people that use plants in order to treat this disease. This I did to have a better

understanding in the thoughts of Africans related to SCD.

Results

Plant species used against SCD

About 40 articles were reviewed and screened for information about plants that were used traditionally

against SCD. A total of 93 species was found, from 49 different families (see appendix). The best

represented families, containing 5 species or more, were the Leguminosae (12), Apocynaceae (6),

Rubiaceae (5), Euphorbiaceae (5) and Annonaceae (5). This is not really a surprise as they all belong to

the major group Angiosperms which has over 5.000 accepted species’ names (www.theplantlist.org).

From the 93 species, a total of 54 species had been proven to work against SCD, which was 58% of the

total. Almost all of these tests on these plants were done ‘in vitro’, which means the biological technique

was performed in a lab in a test tube, instead of in a living creature. This mostly worked by starting to

take blood samples from adolescent subjects with SCD. The blood was screened first to check if they

actually had SCD and they obtained dried and powdered plant material from the species they wanted to

test. The blood samples were put in contact with the plant extracts at different concentrations. It was

put together on a glass slide, and under the microscope checked for a possible anti-sickling effect

(Mpiana et al., 2007).

Active principles

Of the 54 species studied for their possible effect, active principles were identified for 27 species (50%).

In 21 of these cases, anthocyanins seemed to be responsible for the anti-sickling effect.

Anthocyanins are natural colorants belonging to the flavonoid family. They are commonly distributed

among flowers, fruits, and vegetables. Additionally to their colorful characteristics, they have potent

antioxidant properties. This makes them have an array of health-promoting benefits, as they can protect

against a variety of oxidants through a various number of mechanisms. They are found in all plant tissues

throughout the plant kingdom, but come in many forms which can have different properties (Wang et

al., 1997; Kong et al., 2003).

Red colour

From the total of 93 species found, 48 (51.6%) seemed to have red parts in either their roots, stem,

leaves, fruit, or flowers. Out of the 54 species that had been proven to work, 32 (59.2%) have a red

organ. There does not seem to be a direct relation between red plants, and a possible effect against SCD.

It could be that local Africans prefer to use red plants as they believe the colour of the plant affects its

effectiveness, but as only slightly more than half of the species in the table have red parts, this statement

cannot be proven.

To determine which plant species were the most promising to have an effect against SCD, I first looked at

the species which were cited most often in articles (See Table 1).

Table 1. Plant species used against SCD cited in more than three papers

Species Number of articles

Cajanus cajan 4

Carica papaya 4

Piper guineense 3

Pterocarpus osun 3

Sorghum bicolor 4

Syzygium aromaticum 3

Zanthoxylum zanthoxyloides 4

The plants listed in table 1 all have a proven anti-sickling effect against SCD. Pterocarpus osun is part of

the SCD medicine Niprisan, or renamed Nicosan. This medicine is a product of the extracts of four

different kinds of plants: the seeds of Piper guineense, the fruit of Eugenia caryophyllum, the leaves

of Sorghum bicolor and the stems of Pterocapus osun. The herbal medicine has been used locally among

folk groups in Nigeria to prevent painful crises that are associated with SCD, and seems to have a strong

anti-sickling effect. Although the medicine worked, Nicosan was not really a success. (Iyamu et al., 2002).

There are more promising species, like Justicia secunda, Moringa oleifera,and Vinga unguiculata, which

are currently investigated in Congo to be combined to generate a new medicine to control SCD (Borm,

personal communication).

The African view

African people who are confronted with SCD, either because family members or they themselves have

the disease, are most of the time not familiar with or well informed on the disease. Many Africans

believe SCD is caused by a curse from enemies, the work of ‘’Satan’’ or other supernatural (witchcraft)

factors (Ohaeri et al., 2001). There is also a disease named ‘La rate’ by locals, which looks very familiar to

a symptom of SCD, splenic sequestration (Towns, personal communication). This is a spleen crisis in

which sickled cells block the blood vessels leading out of the spleen, so that the blood stays inside. The

spleen gets very large because of the accumulation of blood, and can feel painful. La rate is described as

a swelling and pain on the left side of the body, and most of the time, just like splenic sequestration,

diagnosed with children. It could be very possible that la rate is actually a symptom of SCD instead of a

disease itself.

Discussion

Unfortunately, there are some gaps present in the table (see appendix). In some of the articles, it was

not clear in which countries the plant species were used, active principles were not mentioned, or the

colour of the plant was not to find out.

Furthermore, as earlier mentioned, could the disease la rate be a symptom of SCD. However, this is still

just a thought and has never been proven. It could be that la rate is actually something very different

from SCD. In that case, the species in the table with ‘La rate’ in the tab ‘Other information’, should be

excluded from the table. More investigation should be done on la rate in Africa, to found out if this

disease is indeed a sign of SCD.

A lot of species, 36.3% to be exact, are from the author P.T. Mpiana. He is a professor at the University of

Kinshasa in Congo (http://www.unikin.cd/index.php?page=pub-chimie) and has spent the last twenty

years on studying medicinal plants on their effectiveness against SCD and publishing the results . It

seems not very reliable if a lot of plant species in the table are only tested, and been proved to have an

anti-sickling effect by only one author. Fortunately, a part of the plant species in Mpiana’s articles are

also mentioned in other articles, but this situation states that more investigation should to be done on all

of these plants and their anti-sickling effect.

Additionally, I think best would be to test these plants in vivo instead of only in vitro, so the results and

conclusions are better related to real SCD in people. The problem is, that there is very little funding

available for research, especially for neglected diseases like SCD. Also, barriers are faced in translating

traditional medicinal knowledge into commercially viable health products. For example insufficient

manufacturing capacity, quality control issues and pricing and distribution (Perampaladas et al., 2010).

Finally, I already mentioned that the red colour of the plants could not be proven to have an effect on

SCD. It could be possible, that the red plants in fact have a placebo effect on the local Africans instead of

being really effective. For example when the plants are red, the same colour as blood, they have the idea

the plants can cure their blood. I mention this again because some of the red species proven in the table

are the outcome of questionnaires, and may not be very reliable.

Conclusion

According to my research, the following species are the most promising to have a potential to reduce

sickle cell anemia related health problems: Cajanus cajan, Carica papaya, Piper guineense, Pterocarpus

osun, Sorghum bicolor, Syzygium aromaticum, Zanthoxylum zanthoxyloides, Justicia secunda, Moringa

oleifera and Vinga unguiculata.

I think definitely more research is needed on these plants and also on other species in the table which

seemed to have a proved effect against SCD.

However, if in time all these plants are investigated and new medication can be produced, there are still

local Africans who will never be able to afford the medicines. What I think would be best is to promote

anti-SCD plants as food instead of expensive medicines. Because when you look at the species registered

in the table, a lot of them are actually very common food crops. In the tab ‘Genus and Species

PLANTLIST.ORG’, I marked the common food crops with a ‘*’. The common food crops with a proven

anti-sickling effect, I marked with a ‘**’. There are actually nine species with one asterisk, and nine more

species with two asterisks. These are crops, fruits, herbs or spices, that people can simply buy on a

market or even grow on their own land. If more health education is given on SCD and the locals are being

told about these species, they may benefit and control the SCD symptoms by eating these plant species

on daily basis.

Acknowledgements

I would like to express my very great appreciation to postdoc researcher Tinde van Andel, my supervisor

in this research project. Special thanks to her and all her effort and time on making this research possible

for me.

I would also like to thank Julie-Anne Borm, for her expertise and dedication on the subject. I would finally

like to extend my thanks to PhD Candidate Alexandra Towns, for helping me with the table.

References

Articles

Adejumo, O. E., Owa-Agbanah, I. S., Kolapo, A. L., Ayoola, M.D., 2011. Phytochemical and

antisickling activities of Entandrophragma utile, Chenopodium ambrosioides and Petiveria

alliacea. Journal of Medicinal Plants Research Vol. 5(9), pp. 1531-1535.

Adejumo, O.E., Kolapo, A.L., Roleola, O.P., Kasim, L.S., 2010. In vitro antisickling activities and

phytochemical evaluation of Plumbago zeylanica and Uvaria chamae. African Journal of

Biotechnology Vol. 9(53), pp. 9032-9036.

Adejumo, O.E., Kolapo, A.L., Folarin, A.O., 2012. Moringa oleifera Lam. (Moringaceae) grown in

Nigeria: In vitro antisickling activity on deoxygenated erythrocyte cells. J Pharm Bioallied Sci.

2012 Apr-Jun; 4(2): 118–122.

Adesina, S.K., 2005. The Nigerian Xanthoxylum; Chemical and Biological Values. African Journal

Traditional, Complementary and Alternative Medicines; 2 (3): 282-301.

Afolabi, I.S., Osikoya, I.O., Fajimi, O.D., Usoro, P.I., Ogunleye, D.O., Bisi-Adeniyi, T., Adeyemi,

A.O., Adekeye, B.T., 2012. Solenostemon monostachyus, Ipomoea involucrata and Carica papaya

seed oil versus Glutathione, or Vernonia amygdalina: methanolic extracts of novel plants for the

management of sickle cell anemia disease. BMC Complementary and Alternative Medicine,

12:262.

Akinsulie, A.O., Temiye, E.O., Akanmu, A.S., Lesi, F.E., Whyte, C.O., 2005. Clinical evaluation of

extract of Cajanus cajan (Ciklavit) in sickle cell anaemia. Journal of Tropical Pediatrics Volume 51,

Issue 4Pp. 200-205.

Ameh, S.J., Tarfa, F.D., Ebeshi, B.U., 2012. Traditional herbal management of sickle cell anemia:

lessons from Nigeria. Anemia Volume 2012, Article ID 607436, 9 pages.

Bender, M.A., Hobbs, W., 1993. Sickle Cell Disease. Gene Reviews [Internet], University of

Washington: Seattle,WA; 1993; 2003 Sep 15 [updated 2009 Sep 17].

Borm, J., 2013. Milleniumdoel 6 en de… Sikkelcelziekte. TAO nr.2 Jaargang 7.

Cocks, M., Møller, V., 2002. Use of indigenous and indigenised medicines to enhance personal

well-being: a South African case study. Social Science & Medicine Volume 54, Issue 3, Pages

387–397.

Egunyomi, A., Moody, J.O., Eletu, O.M., 2009.

Antisickling activities of two ethnomedicinal plant recipes used for the management of sickle cell

anaemia in Ibadan, Nigeria. African Journal of Biotechnology Vol. 8 (1), pp. 020-025.

Elekwa, I., Monanu, M.O., Anosike, E.O., 2003. Studies on the effect of aqueous extracts of

Garcinia kola seed on the human erythrocytes adenosine triphosphatase of HbAA, HbAS, and

HbSS genotypes. Global J. Med Sci. 2(2). 107-114.

Elekwa, I., Monanu, M.O., Anosike, E.O., 2005. In vitro effects of aqueous extracts of Zanthxylum

macrophyla roots on adenosine triphosphatases from human erythrocytes of different

genotypes. Biokemistri; 17(1).19-25.

Elekwa, I., Monanu, M.O., Anosike, E.O., 2005. In vitro effects of aqueous extracts of Zanthxylum

macrophyla roots on adenosine triphosphatases from human erythrocytes of different

genotypes. Biokemistri; 17(1).19-25.

Emond, A.M., Collis, R., Darvill, D., Higgs, B.A., Maude, G.H., Serjeant, G.R., 1985. Acute splenic

sequestration in homozygous sickle cell disease: Natural history and management. The Journal of

Pediatrics Volume 107, Issue 2, Pages 201–206.

Ijeoma, U.F., Aderonke, S.O., Ogbonna, O., Augustina, M.A., Ifeyinwa, C.N., 2011. Antinociceptive

and anti-inflammatory activities of crude extracts of Ipomoea involucrata leaves in mice and rats.

Asian Pacific Journal of Tropical Medicine Volume 4, Issue 2, Pages 121–124.

Imaga, N.A., 2013. Phytomedicines and Nutraceuticals: Alternative Therapeutics for Sickle Cell

Anemia. The Scientific World Journal Volume 2013, Article ID 269659, 12 pages.

Imaga, N.A., Gbenle, G.O., Okochi, V.I., Adenekan, S., Duro-Emmanuel, T., Oyeniyi, B., Dokai,

P.N., Oyenuga, M., Otumara, A., Ekeh, F.C., 2010. Phytochemical and antioxidant nutrient

constituents of Carica papaya and parquetina nigrescens extracts. Scientific Research and Essays

Vol. 5(16), pp. 2201-2205.

Iyamu, E.W., Turner, E.A., Asakura, T., 2002. In vitro effects of NIPRISAN (Nix-0699): a naturally

occurring, potent antisickling agent. British Journal of Haematology, Volume 118, Issue 1, pages

337–343.

Kong, J., Goh, N., Chia, T., Brouillard, R., 2003. Analysis and biological activities of anthocyanins.

Phytochemistry, Volume 64, Issue 5, Pages 923–933.

Mehanna, A. S., 2001. Sickle Cell Anemia and Antisickling Agents Then and Now. Current

Medicinal Chemistry, Volume 8, Number 2, pp. 79-88(10).

Mgbemene, C.N., Ohiri, F.C., 1999. Anti-sickling potential of Terminalia catappa leaf extract.

Pharmaceutical biology; 37(2):152-154.

Moody, J.O., Ojo, O.O., Omotade, O.O., Adeyemo, A.A., Olumese, P.E., Ogundipe, O.O., 2003.

Anti-sickling potential of a Nigerian herbal formula (ajawaron HF) and the major plant

component (Cissus populnea L. CPK). Phytotherapy Research Volume 17, Issue 10, pages 1173–

1176.

Moody, J.O., Robert, V.A., Connolly, J.D., Houghton, P.J., 2003. Anitinflammatory activities of

methanol extracts and an isolated furanoditerpene constituent of Sphenocentrum jollyanum

Pierre (Menispermaceae). J. ethnopharmacol; 104(1-2): 67-91.

Moriguchi, T., Takasugi, N., Itakura, Y., 2001. The effects of AGED garlic extract on lipid

peroxidation and deformability of erythrocytes. American society for Nutritional sciences. J.

Nutr. vol. 131 no. 3 1016S-1019S.

Mpiana, P.T., Balanganayi, E.K., Kanangila, A.B., Kalonda, E.M., Ngbolua, K.N., Tshibangu, D.S.T.,

Atibu, E.K., Lumbu, J.B.S, 2009.

The activity against sickle cell and thermodegradation of anthocyanins extracted from Sterculia

quinqueloba and Ficus capensis. International Journal of Biological and Chemical Sciences Vol. 3

No. 3 pp. unpaginated.

Mpiana, P.T., Lombe, B.K., Ombeni, A.M., Ngbolua, K.N., Tshibangu, D.S.T., Wimba, L.K.,

Tshilanda, D.D., Mushagalusa, F.K., Muyisa, S.K., 2013. In Vitro Sickling Inhibitory Effects and

Anti-Sickle Erythrocytes Hemolysis of Dicliptera colorata C. B. Clarke, Euphorbia hirta L. and

Sorghum bicolor (L.) Moench. Open Journal of Blood Diseases, 3, 43-48.

Mpiana, P.T., Mudogo, V., Ngbolua, K.N., Tshibangu, D.S.T., Shetonde, O.M., Mbala, M.B., 2007.

In vitro Antisickling Activity of Anthocyanins from Ocimum basilicum L. (Lamiaceae).

International Journal of Pharmacology 3, 4, 371--.

Mpiana, P.T., Mudogo, V., Tshibangu, D.S., Kitwa, E.K., Kanangila, A.B., Lumbu, J.B., Ngbolua,

K.N., Atibu, E.K., Kakule, M.K., 2008. Antisickling activity of anthocyanins from Bombax

pentadrum, Ficus capensis and Ziziphus mucronata: photodegradation effect. Journal of

Ethnopharmacology Volume 120, Issue 3, Pages 413–418.

Mpiana, P.T., Mudogo, V., Tshibangu, D.S.T., Ngbolua, K.N., Tshilanda, D.D., Atibu, E.K., 2009.

Antisickling activity of anthocyanins of Jatropha curcas L.. Chemistry and medicinal value pp. 83-

90.

Mpiana, P.T., Ngbolua, K.N., Bokota, M.T., Kasonga, T.K., Atibu, E.K., Tshibangu, D.S., Mudogo, V.,

2010. In vitro effects of anthocyanin extracts from Justicia secunda Vahl on the solubility of

haemoglobin S and membrane stability of sickle erythrocytes. Blood Transfus.; 8(4): 248–254.

Mpiana, P.T., Tshibangu, D S., Shetonde, O.M., and Ngbolua, K.N., 2007. In vitro

antidrepanocytary actvity (anti-sickle cell anemia) of some congolese plants. Phytomedicine

14(2-3):192-195.

Mpiana, P.T., Tshibangu, D.S.T., Shetonde, O.M., Ngbolua, K.N., 2007.

In vitro antidrepanocytary actvity (anti-sickle cell anemia) of some congolese plants.

Phytomedicine, Volume 14.

Mpiana, P.T., Ngbolua, K.N., Mudogo, V., Tshibangu, D.S.T., Atibu, E.K., Tshilanda,

D.D., Misengabu, N.M., 2011.

Anti Sickle Erythrocytes Haemolysis Properties and Inhibitory Effect of Anthocyanins Extracts

of Trema orientalis (Ulmaceae) on the Aggregation of Human Deoxyhemoglobin Sin vitro. J. Med.

Sci., 11 (3): 129-137.

Ngemenya, M.N., Mbah, J.A., Tane, P., Titanji, V.P.K., 2006. Antibacterial effects of some

Cameroonian medicinal plants against common pathogenic bacteria. African Journal of

Traditional, Complementary and Alternative Medicines Vol. 3, No. 2, pp. 84-93.

Nsimbaa, M.M., Yamamotoa, C., Lamib, J.N., Hayakawac, Y., Kajia, T., 2013. Effect of a Congolese

herbal medicine used in sickle cell anemia on the expression of plasminogen activators in human

coronary aortic endothelial cells culture. Journal of Ethnopharmacology Volume 146, Issue 2,

Pages 594–599.

Nwaoguikpe, R.N., Uwakwe, A.A., 2008. In vitro antisickling effects of Xylopia Aethiopica and

Monodora Myristica. Journal unknown.

Oduola, T., Adeniyi, F.A.A., Ogunyemi, E.O., Bello, I.S., Idowu, T.O., 2006. Antisickling agent in an

extract of unripe pawpaw (Carica papaya): Is it real? African Journal of Biotechnology 5 (20):

1947-1949.

Ohaeri, J.U., Shokunbi, W.A., 2011. Attitudes and belieft of relatives of patients with sickle cell

disease. East African Medical Journal Vol. 78 No. 4.

Ohnishi, S.T., Ohnishi, T., 2001. In vitro effects of AGED garlic extract and other nutritional

supplements on sickle cell erythrocytes. J. Nutr. vol. 131 no. 3 1085S-1092S.

Okpuzor, J., Adebesin, O., 2006. Membrane stabilizing effect and antisickling activity of Senna

podocarpa and Senna alata. 31st

congress for European biochemical societies, Instanbul, Turkey.

Onwubiko, H.A., 2010. The Anti-Sickling Properties of Ethanol Extracts of Euphorbia heterophylla

and Moringa oleifera Leaves. Plant Products Research Journal, Vol 14.

Orhue, N.E., Nwanze, E.A.C., 2006. Scoparia dulcis reduces the severity of Trypanosome brucei

induced hyperlipidemia in the rabbit. African Journal of Biotechnology; 5(10): 883-887.

Orhue, N.E.J., Nwanze, E.A.C., Okafor, A., 2005. Serum total protein, albumin and globulin levels

in Trypanosoma brucei infected rabbits: Effects of orally administered Scoparia dulcis. African

Journal of Biotechnology. 4(10):1152-1155.

Ouattara, B., Angenot, L., Guissou, P., Fondu, P., Dubois, J., Frédérich, M., Jansen, O., van

Heugen, J., Wauters, J., Tits, M., 2004. LC/MS/NMR analysis of isomeric divanilloylquinic acids

from the root bark of Fagara zanthoxyloides Lam. Phytochemistry 65(8):1145-1151.

Ouattara, B., Jansen, O., Angenot, L., Guissou, I.P., Frédérich, M., Fondu, P., Tits, M., 2009.

Antisickling properties of divanilloylquinic acids isolated from Fagara zanthoxyloides Lam.

(Rutaceae). Phytomedicine Volume 16, Issues 2–3, Pages 125–129.

Ouedraogo, S., Traore, A., Lompo, M., Some, N., Sana, B., Guissou, I.P., 2011.

Vasodilator effect of Zanthoxylum zanthoxyloïdes, Calotropis procera and FACA, a mixture of

these two plants. International Journal of Biological and Chemical Sciences , Vol 5, No 4.

Oyedapo, O.O., Famurewa, A.J., 1995. Antiprotease and Membrane Stabilizing Activities of

Extracts of Fagara Zanthoxyloides, Olax Subscorpioides and Tetrapleura Tetraptera.

Pharmaceutical Biology 33: (1)65 – 69.

Perampaladas, K., Masum, H., Kapoor, A., Shah, R., Daar, A.S., Singer, P.A., 2010. The road to

commercialization in Africa: lessons from developing the sickle-cell drug Niprisan. BMC

International Health and Human Rights, 10(Suppl 1):S11

Rahmatullah, M., Samarrai, W., Jahan, R., Rahman, S., Sharmin, N., Miajee, Z.U.M.E.U.,

Chowdhury, M.H., Bari, S., Jamal, F., Bashar, A.B.M.A., Azad, A.K., Ahsan, S., 2010.

An Ethnomedicinal, Pharmacological and Phytochemical Review of Some Bignoniaceae Family

Plants and a Description of Bignoniaceae Plants in Folk Medicinal Uses in Bangladesh. Advances

in Natural and Applied Sciences, 4(3): 236-253.

Sofowora, E.A., Issac-Sodeye, W.A., 1971. Reversal of sickling and crenation in erthrocytes by the

root of Fagara xanthoxyloides. LIoydia; 34: 383.

Steinberg, M.H., 1999. Management of Sickle Cell Disease. N Engl J Med 1999; 340:1021-1030.

Thomas, K.D., Ajani, B., 1987. Antisickling agent in an extract of unripe pawpaw fruit (Carica

papaya). Transactions Royal Soc. Trop Med & Hyg. 81: 510-511.

Tshilolo, L., Aissi, L.M., Lukusa, D., Kinsiama, C., Wembonyama, S., Gulbis, B., Vertongen, F., 2009.

Neonatal screening for sickle cell anaemia in the Democratic Republic of the Congo: experience

from a pioneer project on 31 204 newborns. Journal Clin. Pathol.;62:35-38.

Ugbor, C., 2006. The effect of vegetable extracts on the antisickling potential of Aloe vera.

www.biochemistry.org/meetings/ abstracts/BS2006/BS20060567.pdf.

Vanhaelen-Fastre, R., Vahaelen, M., Lo, I., Toppet, M., Ferster, A., Fondu, P., 1999. In vitro

antisickling activity of a rearranged limonoid isolated from Khaya senegalensis. Planta medica

65(3): 209-212.

Wang, H., Cao, G., Prior, R.L., 1997. Oxygen Radical Absorbing Capacity of Anthocyanins.

J. Agric. Food Chem., 45 (2), pp 304–309.

Links

http://google.com

http://scholar.google.nl/

http://theplantlist.org

http://wikipedia.com

http://www.afro.who.int/en/clusters-a-programmes/dpc/non-communicable-diseases-

managementndm/programme-components/sickle-cell-disease.html, World Health Organization;

Regional office for Africa

http://www.hematologienederland.nl/sikkelcelziekte

http://www.ncbi.nlm.nih.gov/pubmed

http://www.nhlbi.nih.gov/health/health-topics/topics/sca/

http://www.nhlbi.nih.gov/health/health-topics/topics/sca/signs.html

http://www.unikin.cd/index.php?page=pub-chimie .