j o u r n a l o f h e r b a l m e d i c i n e 4 ( 2 0 1 4 ) 224–234

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Original Research Article

Ethnopharmacological survey of herbal treatmentof malaria in Lagos, Southwest Nigeria

I.O. Isholaa, I.A. Oreagbaa,∗, A.A. Adeneyeb, C. Adirijea,K.A. Oshikoyab, O.O. Ogunleyeb

a Department of Pharmacology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos,Idi-Araba, P.M.B. 12003, Lagos, Nigeriab Department of Pharmacology, Faculty of Basic Medical Sciences, Lagos State University College of Medicine, 1-5Oba Akinjobi Way, G.R.A. Ikeja, Lagos, Nigeria

a r t i c l e i n f o

Article history:

Received 24 February 2013

Received in revised form

10 June 2014

Accepted 8 August 2014

Available online 17 August 2014

Keywords:

Indigenous plants

Antimalarial

Malaria

Traditional herbal medicine

a b s t r a c t

Aim: This ethnobotanical survey was conducted to investigate the pattern of treatment

practices and medicinal plants used for malaria therapy in Lagos State, Nigeria.

Methods: Focus group discussions were initially held with traditional herbal medicine prac-

titioners (THMPs), herb retailers (HRs), elderly people, nursing mothers and undergraduate

students to identify who had ever used herbs to treat malaria fever. Participants were

recruited from various local government areas in Lagos. Five hundred and fifty eligible

participants were interviewed with a semi-structured questionnaire purposely designed to

collect information on the type, composition, method of preparation, dosage, and mode of

administration of herbal preparations used as local antimalarial therapies.

Results: Herb sellers (36.4%), THMPs (27.3%), nursing mothers (27.3%), undergraduate stu-

dents with knowledge of herb use (5.5%), and elderly people with knowledge of herb use

(3.5%) were the participants in this study. Forty one plant species belonging to 27 families

were identified as being used locally for antimalarial herbal recipes. Of these Enantia chlo-

rantha (31.5%), Carica papaya (27.5%), Azadirachta indica (25.5%), Cymbopogon citrates (23.3%),

Morinda lucida (22.7%), Mangifera indica (21.1%), and Alstonia boonei (20.5%) were the most

frequently used plants. The stem barks, roots, leaves or whole plants were the plant parts

most frequently used. These were used either alone or in combination with other plant

parts. Different plant species were also used in combinations.

Conclusion: Indigenous plants with potential antimalarial properties were identified in this

survey. The plants could serve as good sources of new antimalarial plant therapies.

© 2014 Elsevier GmbH. All rights reserved.

∗ Corresponding author. Tel.: +234 8023519433.E-mail addresses: oreagbai@yahoo.com, ibn20032002@yahoo.com, o

http://dx.doi.org/10.1016/j.hermed.2014.08.0012210-8033/© 2014 Elsevier GmbH. All rights reserved.

ishola@cmul.edu.ng (I.A. Oreagba).

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. Introduction

he major burden imposed by malaria on the sub-Saharanfrican population is well recognized. Plasmodium falciparum is

esponsible for an estimated 300–500 million clinical attacksf malaria globally, and over one million under-five child-ood deaths in sub-Saharan Africa (Snow et al., 2005). Theisease accounts for an estimated loss of 44.7 million disabil-

ty adjusted life years (DALYs), more than 80% of which areurrently concentrated in sub-Saharan Africa (WHO, 2002). Inhe absence of effective intervention strategies and the rapidncrease of drug resistance, the number of malaria cases mightouble over the next 20 years (Breman, 2001).

More than 15% of those who survive an acute attack oferebral malaria are left with severe neurological deficits, andarying degrees of brain damage that may impair learning andevelopment (Holding and Snow, 2001). The direct economicosts of malaria are enormous and weigh particularly heavilyn resource-poor countries. Recent research has shown a closeorrelation at the country level between the rate of economicevelopment and the burden of malaria, even after adjustingor potential confounding factors (Sachs and Malaney, 2002).his indicates that malaria is an important constraint on eco-omic progress.

It is not surprising that P. falciparum, the species of malariaarasite responsible for the majority of malaria deaths, is nowighly resistant to most of the available antimalarial drugs.his has been exacerbated by self-medication, empiric treat-ent of malaria, and use of counterfeit drugs (Oshikoya and

enbanjo, 2010). Since the late 1950s, resistance to chloro-uine developed originally in two regions – South Americand Southeast Asia – and is now widespread throughout theorld. Resistance of P. falciparum to other antimalarial drugs

ncluding sulfadoxine-pyrimethamine and mefloquine fol-owed within a few years of their introduction (Mockenhaupt,995). Cross-resistance between halofantrine and mefloquines suggested by reduced response to halofantrine when usedo treat mefloquine failures (ter Kuile et al., 1993).

Artemisinin-based combination therapy (ACT) is used ashe first line treatment of uncomplicated P. falciparum malarian over 100 countries and is the cornerstone of malaria con-rol and elimination programmes in these areas. However,espite the high potency and rapid parasite killing action ofCTs there is a high rate of recrudescence associated with aonotherapy and recrudescence is not uncommon even when

CT is used (Ittarat et al., 2003). Compounding this problemre reports that some parasites in Cambodia, a known centref drug resistance, have decreased in vivo sensitivity to ACTs.his raises serious concerns for the development of resistance

o the ACTs in the field even though no major phenotypic andenotypic changes yet have been identified in these parasitesCheng et al., 2012; Hoyer et al., 2012). Therefore, there is anrgent need to find alternative and highly potent compounds

or malaria treatment (Marfurt et al., 2012).The use of medicinal plants may hold the key to new and

ore effective antimalarial treatments in the future. Thus,

here is a need to shift attention to natural products as raw

aterials for the development of new antimalarial treatmentsnd, if possible, a vaccine with minimal side effects. In this

e 4 ( 2 0 1 4 ) 224–234 225

regard, the indigenous medicinal plants in Nigeria that areused in combating malaria are yet to be fully explored.

Considering the rich flora diversity in Nigeria, it is imper-ative to identify and develop the types of medicinal plants(including the various species and plant parts) used as herbaltreatment for malaria in Lagos state, Nigeria. One of the objec-tives of this study was to discover how the various plantspecies and parts are combined for use and their potentialadverse effects following short and prolonged use.

2. Materials and methods

2.1. Study area

Lagos is a commercial centre in Nigeria with a little over 17.5million inhabitants, a yearly growth rate of 3.2% and the sec-ond most populous city in the country (Nigerian PopulationCommission, 2007).

Twenty two per cent of the 787 square miles of the state ismade up of lagoons and creeks that stretch over 180 km alongthe coast of the Atlantic Ocean. It extends westward to Bada-gry and eastwards to Epe, terminating in the riverine area ofLekki. Lagos is a multi-sociocultural melting point attractingboth Nigerians and non-Nigerians alike, due to its economicand sociopolitical importance. This has led to migration fromthe rural areas within the country to the city, resulting in thediversified ethnic composition of inhabitants of the state. Theindigenes of Lagos are mostly Aworis, Eguns and Ijebus. Thereare five major administrative divisions (Ikeja, Epe, Ikorodu,Badagry and Lagos Island) in the state as shown in Fig. 1. Thestudy was therefore conducted in the five divisions to allow abetter overall coverage of the entire state.

Of the 20 Local Government Areas (LGAs) in Lagos State and37 Council Development Areas (CDAs), 14 LGAs were selectedfor the study: Badagry, Epe and Ikorodu are suburb/ruralin nature while Apapa, Eti-Osa, Ibeju-Lekki, Kosofe, LagosMainland, Lagos Island, Mushin, Ojo, Oshodi-Isolo, Shomolu,Surulere, are urban settlements. The study was conductedover a period of three months – June–August, 2010. A clus-ter sampling technique was employed for the selection of theLGAs and simple random sampling technique for the selectionof the participants.

2.2. Participant recruitment

Participants were recruited from both urban and rural areasof the state. The urban areas are densely populated withpeople of various tribes, occupations, social classes, religionsand levels of literacy. However, the rural areas are populatedmostly by indigenous Lagosians and few foreigners from theneighbouring states and countries. The rural communitiesgenerally lack the basic amenities of life including modernhealth facilities, pipe borne water, good roads and housing.The THMPs and HRs in each community were approachedthrough their leaders, while elderly people, nursing moth-

ers and undergraduate students were approached throughthe community leaders. Identified participants were initiallyinvited to participate in group discussions to determine theireligibility. Only the individuals older than 25 years of age who

226 j o u r n a l o f h e r b a l m e d i c i n e 4 ( 2 0 1 4 ) 224–234

win

Fig. 1 – Map of Lagos state sho

were able to demonstrate a good knowledge of malaria feverand had used medicinal plants more than once to treat malariafever were considered as eligible participants.

2.3. Questionnaire design (Appendix I)

The instrument used for the study was a WHO standard-ized semi-structured self-administered questionnaire (Asaseet al., 2005; Ajaiyeoba et al., 2006). Information such as thedemographic structure of the study population, i.e. age groups,occupation and sex of individuals, was generated. Respon-dents were questioned on the parts of plants employed in thetreatment of malaria, mode of preparation, route of admin-istration, benefits and side effects (if any) of the herbalmedicines they used plus cultural understanding of fever.

2.4. Ethical considerations

The study was approved by the ethics and research com-mittee of the College of Medicine, University of Lagos. Thepurpose of the study was explained to each participant andtheir informed consent obtained.

2.5. Data analysis

Data obtained from the questionnaires was analyzed using theEpi Info. Ink software (version 3.5.1). The analyzed data waspresented in simple descriptive statistics such as percentages.

g the local government areas.

3. Results

3.1. Demography

A total of 550 randomly selected participants were inter-viewed using a questionnaire. They included herb sell-ers (36.4%; n = 200), THMPs (27.3%; n = 150), mothers whoare currently nursing a child (27.3%; n = 150), elderlypeople (3.5%; n = 20), and undergraduate students (5.5%;n = 30).

The socio-demographics of the participants are presentedin Table 1. Their median age was 51 years [Interquartile range(IQR) 25–85]. The respondents were mainly female (68.5%;n = 377). About one-third of the respondents (36.5%) had noformal education.

3.2. Herbal recipes

Forty one plant species belonging to 27 families were usedin herbal antimalarial recipes. Table 2 shows the list ofherbs used by the participants for malaria treatment. Themost frequently used plants were Enantia chlorantha Oliv.(31.5%); Carica papaya L. (27.5%), Azadirachta indica A. Juss

(25.5%), Cymbopogon citratus (DC) Stapf., (23.3%), Morinda lucida(Benth.) (22.7%), Mangifera indica (L.) (21.1%), and Alstoniaboonei De Wild. (20.5%). These plants belong to the familiesAnnonaceae, Caricaceae, Meliaceae, Rubiaceae, Anacardiceae

j o u r n a l o f h e r b a l m e d i c i n e 4 ( 2 0 1 4 ) 224–234 227

Table 1 – Socio-demographic characteristics of therespondents.

Demographiccharacteristics

Frequency Percentage %(C.I.)

Type of respondentTHMPs 150 27.3 (23.6–31.2)Herb seller 200 36.4 (32.4–40.6)Mothers 150 27.3(23.6–31.2)Elderly people 20 3.6 (2.3–5.7)Othersa 30 5.5 (3.8–7.8)

Age (years)25–35 80 14.5 (11.8–17.8)36–45 139 25.3 (21.7–29.2)46–55 147 26.7 (23.1–30.7)56–65 133 24.2 (20.7–28.0)66–75 45 8.2 (6.1–10.9)76–85 6 1.1 (0.4–2.5)

GenderFemale 377 68.5 (64.4–72.3)Male 173 31.5 (27.7–35.6)Christian 94 35.3 (31.3–39.4)Islam 346 62.9 (58.7–66.9)Traditional religion 10 1.8 (0.9–3.4)

Level of educationNone 201 36.5(32.7–40.3)Primary school 109 19.8 (16.0–23.9)Secondary school 199 36.2 (32.4–40.0)Tertiary school 41 7.5 (3.7–11.5)

OccupationCivil servant 30 5.4 (3.5–7.4)Student 19 3.5 (2.2–5.5)Herb seller/THMPs 501 91.1 (88.7–93.6)

Marital statusDivorced 18 3.3(2.0–5.2)Married 405 73.6 (69.7–77.2)Separated 67 12.2 (9.6–15.3)Single 60 10.9 (8.5–13.9)

C.I., confidence interval set at 95%; S.D., standard deviation.

apT

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Fig. 2 – Frequency of solvent use for herbal extraction as

who have ever used herbal antimalarials were nausea, vomi-

THMPs, traditional herbal medicine practitioners.a Others represent younger adults and undergraduate students.

nd Apocynaceae, respectively. Previously reported toxicityrofiles related to the aforementioned plants are included inable 2.

The medicinal plants with a significant antimalarial activ-ty that are used as single plant prescriptions are presented inable 3. Eight antimalarial recipes were based on a combina-ion of two plants; three recipes were based on a combinationf three plants; whilst seven antimalarial herbal recipes wereased on a combination of four or more plants (Table 4). Otherlants as presented in Table 5 were used as adjuncts to theain herbal recipes for malaria therapy and are mostly used

o treat coated tongue and associated anaemia.

.3. Herbal preparation

erbal remedies were either prepared from dry plant partsr freshly collected plants. The participants affirmed howeverhat either the use of the dry or fresh plant parts were effective,epending on their availability as some of the plants parts

ay not be available within the locality. Scarce plants or those

hreatened by extinction are usually grown domestically orultivated. Some THMPs even preserve parts of these plants

reported by the respondents.

by cutting them into smaller pieces including those that areseasonal. The preparation of the plants into medicine could bein the form of a drink called ‘agbo’ or powder called ‘agunmu’which may be sprinkled into pap for drinking or mixed insidepalm wine or water to make a drink.

3.4. Solvent used for the herbal antimalarialpreparation

Most of the participants preferred to use locally brewed alco-hol (“Ogogoro”), fermented maize water (“omi dun”), and asoft drink (preferably 7Up®) as the solvents for ‘soaking’ theirantimalarial plant parts (Fig. 2).

3.5. Traditional extraction and administrationmethods

According to the respondents, various methods are used in thepreparation of herbal remedies for the treatment of malariain Lagos state which included decoction or infusion in coldwater or other solvents (alcohol/fermented maize/7up®). Forexample the bark of E.chlorantha is cut into small pieces andsoaked in alcohol or 7up® and the infusion consumed for thetreatment of malaria.

All the respondents, including the THMPs, preferred torecommend a cup-full (about 50 cl) of aqueous alcoholic prepa-rations 2–3 times daily or as much as possible until symptomsof malaria disappear. About 40% of the respondents suggestedbathing with or inhaling the steam of the aqueous prepara-tions for 4–10 days, especially for patients’ high fever.

3.6. Observed side-effects

The majority of the respondents (97.1%; n = 534) claimed thatthere were no side effects observed with the use of medici-nal herbs, while a few (2.9%; n = 16) admitted to experiencingsome side effects. Common side effects experienced by those

ting, increased sweating and diuresis. Frequent micturitionwas considered by the THMPs as a measure of effectivenessof the herbal remedies.

228 j o u r n a l o f h e r b a l m e d i c i n e 4 ( 2 0 1 4 ) 224–234

Table 2 – Medicinal plants used in malaria therapy in Lagos State, Southwest Nigeria.

S.No.

Scientificname

(species)

Familynames

Localnames

(language)

Commonnames

Parts used Frequency(%)

Toxicity

1 Sphenocentrumjollyanum Pierre

Menispermaceae Akerejupon (y) Unknown Roots 5.6 –

2 Rauwolfiavomitoria Afz.

Apocynaceae Asofeyeje (y) Unknown Roots, stembark, leaves

7.5 Hepatotoxicandnephrotoxic(1)

3 Enantiachlorantha Oliv.

Annonaceae Awopa (y)Dokita igbo (i)

Africanyellow wood

Stem bark 31.5 Safe (2)

4 Khayagrandifoliola L.

Meliaceae Oganwo (y) Mahogany Stem bark 8.2 –

5 Melicia excelsa(Welw.)

Moraceae Iroko (y) Iroko Root, stembark

4.7 –

6 Senna siamea(Lam.)

Caesalpiniaceae Kasia (y) Senna Stem bark 3.6 –

7 Azadirachtaindica (A Juss)

Meliaceae Dogonyaro Neem Stem bark,leaves

25.5 Multi-organdamage (3)

8 Mangifera indica(Linn.)

Anacardiaceae Mangoro (y)Mangulo (i)

Mango Stem bark,leaves

21.1 Hepatotoxic(4)

9 Physalisangulata L.

Solanaceae Koropo (y) Leaves, wholeplant

5.3 –

10 Chromolaenaodorata L.

Compositae Ewe Awolowo (y) Siam weed Root, leaves 5.3 –

11 Carica papaya(Linn.)

Caricaceae Ibepe dudu (y)Odudu oyibo (i)

Pawpaw Leaves,unripe fruit

27.5 Hepatotoxic(5)

12 Psidium guajavaL.

Myrtaceae Gilofa (y) Guava Stem bark,leaves

11.6 Hepatotoxic(6)

13 LecaniodiscuscupanioidesPlanch.exBenth

Sapindaceae Akika (y) Roots 5.8 –

14 Curcuma longaL.

Zingiberaceae Laali-pupa (y) Turmeric Rhizome, leaf 15.6 –

15 Zingiberofficinale Rosc.

Zingiberaceae Ata-ile (y) Ginger Rhizome 9.1 –

16 Nauclea latifoliaSm.

Rubiaceae Gberesi (y)Ubaru inu (i)

African peach Root, stembark, leaves

16.2 –

17 Citrusaurantifolia(Christm.)Swingle

Rutaceae Osan wewe (y)Oroma nkirisi (i)

Lime Root, stembark,stem-twigs,leaves, fruit

16.0 –

18 Citrusaurantium L.

Rutaceae Osanganinganin(y) Sour lime Root, stembark,stem-twigs,leaves, fruit

9.8 –

19 Citrus paradisi L. Rutaceae Osan gerepu (y) Grape Fruit,stem-twigs,leaves, root

14.4 –

20 Gossypiumbarbadense L.

Malvaceae Owu (y) Cotton Leaves 4.7 Anti-fertility(7)

21 Gossypiumhirsutum L.

Malvaceae Ela owu(y) Cotton Leaves 3.1 –

22 Alstonia booneiDe Wild.

Apocynaceae Ahun (y)Ebu (i)

Stool wood Root, stembark, leaves

20.5 Nephrotoxic(8)

23 Parquetinanigrescens Afz.

Periplocaceae Ogbo (y) Whole plant,leaves

9.5 –

24 Ananas comosusLinn.

Bromeliaceae Ope-Oyinbo dudu(y)

Pineapple Unripe fruit 15.5 –

25 Xylopiaaethiopica(Dunal) A. Rich

Annonaceae Erinje(y) Fruits, stembark, leaves

7.5 Nephrotoxic(9)

26 Morinda lucida(Benth.)

Rubiaceae Oruwo (y)Eze ogwu (i)

Brimstonetree

Stem bark,leaves

22.7 Safe (10)

j o u r n a l o f h e r b a l m e d i c i n e 4 ( 2 0 1 4 ) 224–234 229

Table 2 – (Continued)

S.No.

Scientificname

(species)

Familynames

Localnames

(language)

Commonnames

Parts used Frequency(%)

Toxicity

27 Vernoniaamygdalina Del.

Compositae Ewuro (y)Olugbu (i)

Bitter leaf Leaves 9.8 Safe (11)

28 Chrysophyllumalbidum G. Don

Sapotaceae Agbalumo (y)Udara (i)

African starapple

Stem bark,leaves

6.7 –

29 Anacardiumoccidentale L.

Anacardiaceae Kasu (y) Cashew nuttree

Stem bark,leaves

6.5 –

30 Ocimumgratissimum L.

Labiatae Efirin-nla (y)Nchaun (i)

Tea bush Leaves 14.4 Liver necrosis(12)

31 Cymbopogoncitratus DC.

Poaceae Kooko-Oba (y) Lemon grass Leaves 23.3 Obesity (13)

32 Musa sapientumLinn.

Musaceae Ogede wereibile (y)

Banana Fruits 4.5 –

33 Allium sativumL.

Liliaceae Ayuu (y) Garlic Bulb 9.3 Anaemia (14)

34 Solanum nigrumL.

Solanaceae Odu (y) Leaves 4.9 –

35 Ceiba pentandra(L.) Gaertn.

Bombacaceae Araba (y) Kapok tree Leaves 4.2 –

36 DiospyrosmespiliformisHochst. ex A.DC

Ebenaceae Igi dudu (y) Ebony tree Stem bark,leaves

4.0 –

37 Cajanus cajan(L.) Millsp.

Fabaceae Otili (y) Leaves 8.2 –

38 Garcinia kola(Heckel.)

Guttiferae Orogbo (y)Aku–ilu (i)

Bitter cola Stem bark 5.8 –

39 Moringa oleifera(Lam.)

Moringaceae Ewe igbale (y)Okochi egbu

Horse radishtree

Leaves 5.3 –

40 Funtumiaafricana(Benth.)

Apocynaceae Ako-ire (y) Funtumia Root 4.9 –

41 Zanthoxylumzanthoxyloides(Lam.) Zepern.and Timler

Rutaceae Orin ata (y) Root 11.5 –

(y), Yoruba; (i), Igbo; Negli., negligible. Toxicity of plants as reported (1)-Eteng et al. (2009), (2) Agbaje and Onabanjo (1994), (3) Ali (1987), (4) Izunyaet al. (2010), (5) Udoh and Udoh (2005), (6) Onyekwe (2011), (7) Thomas et al. (1991), (8) Oze et al. (2007), (9) Ogbonnia et al. (2008), (11) Challandand Willcox (2009), (12) Effraim et al. (2003), (13) Mishra et al. (1992), (14) Gatsing et al. (2005).

Table 3 – Medicinal plants used for antimalarial therapy: single plant prescriptions.

S. No. Botanical names Parts used Method of extraction Antimalariaactivity

(efficacy)

1 Enantia chlorantha Stem bark Decoction, tincture, infusion (a) and (b)2 Morinda lucida Root, leaves Tincture, infusion (c)3 Azadirachta indica Stem bark, leaves Decoction (d)–(f)4 Alstonia boonei Stem bark Decoction, tincture, infusion (g)5 Nauclea latifolia Stem bark, roots Tincture, infusion (h)6 Rauwolfia vomitoria Roots Infusion (i)7 Funtumia africana Roots Infusion –8 Curcuma longa Rhizome Decoction, tincture –9 Carica papaya Fruit, leaves Infusion (j)

10 Allium sativum Bulb Concoction, tincture (k)11 Lecaniodiscus cupanioides Root Infusion –12 Vernonia amygdalina Leaves Infusion (l)13 Khaya grandifoliola Stem bark Decoction, infusion (i)

References for activity as indicated in last column: (a) Agbaje and Onabanjo (1991), (b) Adjanohoun et al. (1996), (c) Awe and Makinde (1998), (d)MacKinnon et al. (1997), (e) Isah et al. (2003), (f) Obih and Makinde (1985), (g) Tantchou et al. (1986), (h) Benoit-Vical et al. (1998), (i) Zirihi et al.(2005), (j) Bhat and Surolia (2001), (k) Perez et al. (1994), (l) Ngemenya et al. (2006).

230 j o u r n a l o f h e r b a l m e d i c i n e 4 ( 2 0 1 4 ) 224–234

Table 4 – Medicinal plants used for antimalarial therapy: multiple plant prescriptions.

S.No.

2 Plant combinations 3 Plant combinations 4 or more Plantcombinations

1 Alstonia boonei BCapsicum fructescens F

Gossypium barbadense LOcimum gratissimum LCitrus aurantium F

Carica papaya UFCymbopogon citratus LAnanas comosus UFAzadirachta indica B, L

2 Enantia chlorantha BCymbopogon citratus L

Carica papaya FCitrus paradisi FAnanas comosus F

Azadirachta indica B, LCitrus aurantifolia FMangifera indica LMorinda lucida B, L

3 Chrysophyllumalbidum L, BCitrusaurantifolia L, F

Cymbopogon citratus LCurcuma longa RCitrus aurantifolia L

Cajanus cajana LAzadirachta indica BAlstonia boonei BRauwolfia vomitoria L

4 Alstonia boonei BEnantia chlorantha B

Gossypium barbadense LCurcuma longa LCymbopogon citratus LAlstonia boonei L

5 Carica papaya LPsidium guajava L

Enantia chlorantha BNauclea latifolia BCymbopogon citratus LCurcuma longa LCitrus paradisi FCarica papaya UFCitrus aurantifolia FAlstonia boonei BAnanas comosus UF

6 Azadirachta indica LAlstonia boonei B

Morinda lucida LNauclea latifolia LCymbopogon citratus LMoringa oleifera LGarcinia kola FPsidium guajava F

7 Enantia chlorantha BCurcuma longa Rh

Ocimum gratissimum LAnacardium occidentale LLecaniodiscus cupanioides LCurcuma longa LCitrus aurantifolia L

8 Vernonia amygdalina LCitrus aurantium F

F, fruit; L, leaves; B, bark; Rh, rhizome; UF, unriped fruit.

Table 5 – Medicinal plants used as adjuncts to the mainherbal recipes for malaria therapy and their indications.

S. No. Coated tongue Hematinnics(oral thrush)

1 Chrysophyllum albidum (bark) Parquetina nigrescens (leaves)2 Solanum nigrum (leaves) Khaya grandifoliola (bark)3 Anacardium occidentale (bark) Zanthozylum zantholoides

(root)

4 Mangifera indica (bark, leaves)5 Khaya grandifoliola (bark)

4. Discussion

In Nigeria, a large number of plant species have been iden-tified as having antimalarial properties. This study revealedthe most common species and their common combinations

with other plants when administered as antimalarials.The participants interviewed in this survey were able tosuspect malaria fever based on the symptoms of fever,passage of yellow or straw-coloured urine, headache, gen-eral body pains, profuse sweating, poor appetite, chills andrigour, and bitter taste, a common complaint by malariapatients.

There are various plant species belonging to different fam-ilies that were identified in this study as being used for thetreatment of malaria fever. The plants were similar to thoseearlier identified by Odugbemi et al. (2007) in Okeigbo, Ondoand Idowu et al. (2010) in Ogun State; both in SouthwesternNigeria. Oliver (1960) also reported similar plants with anti-

malarial effects many decades ago in Nigeria. Our findingsare also comparable to those describing medicinal plants withantimalarial effects reported in Ghana (UNESCO, 1997; Asaseet al., 2010) and Sierra Leone (Agbovie et al., 2002).

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The efficacy and toxicity demonstrated by some of the anti-alarial plants identified in this study has previously been

ocumented either in vivo or in vitro studies. Allium sativuminn. (family: Alliaceae), for example, is widely used as a foodondiment and spice in Cameroon. It has also been investi-ated for its antimalarial activity (Titanji et al., 2008). Perezt al. (1994) isolated ajoene from this plant, which consider-bly reduced the severity of P. berghei infection in mice and thissolate was found to be non-toxic. Similarly, the aqueous stemark extract of the plant, E. chlorantha, was found to be effec-ive in suppressing Plasmodium yoelii infection in mice and alsoncreased their survival time by 60 days when given orally inrinking fluid at 0.2–150 mg/ml (Agbaje and Onabanjo, 1991).

The ethanolic stem bark extract of E. chlorantha was foundo be effective in clearing the Plasmodium parasites from thelood stream when administered subcutaneously at doses of.05–0.5 mg/g body weight (Agbaje and Onabanjo, 1991). Also,he aqueous extract of the plant given as a drink offered

chemoprophylactic protection against Plasmodium infec-ion for 96 h while the ethanolic extract administered viahe subcutaneous route did not offer any chemoprophylaxis.hus, the aqueous and ethanolic extracts were calculated toave ED50 values of 6.9 mg/g and 0.34 mg/g, respectively, andere both schizonticidal in action. Phytochemical analysisf the plant extracts also revealed the presence of alkaloids,aponins and simple sugars (Agbaje and Onabanjo, 1991).ure compounds have been isolated from some of theselants and the antimalarial activities of these compoundsre either comparable or more active than the conven-ional antimalarial, chloroquine, on sensitive and resistanttrains of P. falciparum (Bakhiet and Adam, 2004). For exampleioassay-guided fractionation of stem bark and leaves extractsf Khaya grandifoliola led to four main active compounds,amely methylangolensate, 7�-acetoxydihydronomilin, 7�-bacunylacetate and 22-hydroxyhopan-3-one which were allhown to have antimalarial effects (Bickii et al., 2000; Bumaht al., 2005). Fractions obtained from the leaf extract of M. lucidaevealed schizontocidal activity against early infection of P.erghei in mice (Awe et al., 1998) while that of the aqueousxtracts of the stem and root of Nauclea latifolia were testednd their antimalarial activity was confirmed on two strainsf P. falciparum. Specifically, the aqueous extract of N. latifolia

nhibited FCB1 strain of P. falciparum mainly at the end of therythrocytic cycle 32nd to 38th hours (Benoit-Vical et al., 1998).ikewise, various studies have reported the in vitro inhibitoryctivities of A. indica Linn. leaf, seed and stem bark extractsgainst the asexual stages of P. falciparum (MacKinnon et al.,997; Udeinya et al., 2008; Lucantoni et al., 2010). The in vitrocreening of purified limonoids from Azarachidta indica Linn.dentified gedunin and nimbolide as the most active anti-

alarial molecules against P. falciparum (MacKinnon et al.,997).

The use of a combination of two or more herbal extractsas existed for decades in cultural systems. For instance, tradi-

ional Chinese medical knowledge and practice revealed thatrtemisia annua was used in combination with other plants

n the treatment of fever (O‘Neill et al., 1987). This synergis-ic effect may be responsible for the increased permeabilityf the plasmodium membrane to antiparasitic substances inhe herbs or an inhibition of plasmodium pump mechanism

e 4 ( 2 0 1 4 ) 224–234 231

for eliminating the drugs (Alexandros, 2007). Despite the ben-efits of polyherbal therapy for malaria, it may result in toxicity,an increased bitter taste of the preparation, and potential foradverse reactions.

The various solvents for herbal preparations mentioned bythe participants were water, fermented maize water, alcoholand a soft drink (specifically 7up®). A higher percentage of theparticipants interviewed, especially in the rural communities,showed preference for the use of extracts using fermentedmaize water which was corroborated by herb sellers inter-viewed in the urban communities. Alcohol extraction wasconsidered useful for antimalarial remedies prepared mainlyfrom hard plant parts like the stem bark, root, and seeds.Thus, preference for a solvent for extraction was determinedby the plant parts constituting the herbal remedies. The par-ticipants also believed that some solvents were more effectivethan others. Some laboratory studies have shown that the effi-cacy of medicinal plants is dependent on the type of solvent(s)used for extraction (Agbaje and Onabanjo, 1991; Muthauraet al., 2007). For example, the methanolic extracts of Flueggeavirosa, Maytenus undata and Maytenus putter lickioides are knownto have a higher percentage of chemo-suppression effect onmalaria parasitaemia in vivo than the water extract of thesame plants. On the contrary, the water extracts of Harunganamadagascariensis and Warburgia stuhlmannii are known to havea higher chemo-suppression effect on malaria parasitaemiathan the methanolic extracts in in vivo studies (Muthaura et al.,2007).

The two main methods of preparation preferred by theparticipants were boiling in water or aqueous extract from fer-mented maize. The plant parts were either soaked or boiled inthe solvents. More preference was shown to boiling than soak-ing the medicinal plants. This is as a result of the general beliefin Nigeria that extraction of the active ingredient(s) containedin the plants is better achieved with the application of heat.Alcohol was never used as a solvent when boiling medicinalplants other than for soaking. Duration of boiling ranged from1 to 2 h on a burning fire wood or cooking stove till a changein colour of the solvent was observed, which is taken as anindication that the active ingredients of the medicinal plantshave fully dissolved.

Soaking was a second choice of preparation which wasgiven less preference by the respondents. In addition to waterand aqueous extracts from fermented maize, the medicinalplants may also be soaked in alcohol. The soft drink (7up®)was specifically used for soaking E. chlorantha (when appliedas monotherapy). This method was preferred by its users asit is a general belief in Nigeria that the ‘ingredients’ would beextracted without being exposed to heat which they believedcould destroy the active ‘ingredients’ in the plants. Soakinginvolves cutting plant parts into small pieces and togetherwith the solvent, storing in corked bottles or containers for2 to 3 days or more. Soaked herbal remedies are always avail-able in some households and are used very often even withoutobvious symptoms of malaria. They are very often used formalaria prophylactics rather than for treatments.

The use of either freshly collected (wet) herbal recipes or

preserved (dry) plant parts seems not to make any differencein its perceived efficacy to the participants. This was con-firmed in the study as the participants showed no peculiar

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preference for either the fresh or dry plants. However, stud-ies had shown that there were quantitative and qualitativedifferences in the essential oil components of fresh and dryplant materials (Fatemeh et al., 2006; Okoh et al., 2008). i.e.dry plant materials might not be as potent as freshly collectedherbs since some of its enzymes may have been denatured orthe heat-labile components could have been destroyed.

Many of the participants claimed they had never experi-enced or observed any side effects from the use of medicinalherbs for malaria treatment. Most adverse effects of the herbalremedies may mimic the symptoms and signs of malariawhich the participants may find very difficult to differenti-ate. This may explain why many of the participants felt thatherbal antimalarials were devoid of adverse effects. The par-ticipants who experienced or observed a few adverse effects ofthe herbal remedies possibly erroneously attributed this to theeffectiveness of the herbs. However, studies have proven thatsome antimalarial herbs have dose dependent side-effects(Awodele et al., 2009). High levels of chemo-suppression ofmalaria parasites, for example, were produced at high dosesof the leaf and root-bark extracts of Vernonia amygdalina (Abosiand Raseroka, 2003). Studies had also shown that some plantsare highly toxic despite their high chemo-suppression of para-sitaemia. M. lucida, one of the most frequently used plants bythe participants, is known to be cytotoxic from in vitro stud-ies (Awodele et al., 2009). The stem bark of the same plantwas also found to be extremely toxic (Ajaiyeoba et al., 2006).Animal studies have shown the extract of the stem bark of A.boonei to be potentially nephrotoxic when given at a high doseor used over a prolonged time (Panda, 1999). The extracts ofCymbopogon citratus however have been reported to produce aninsignificant toxicity profile, hence, they may be consideredto be relatively safe (Iwu, 1993; Adeneye and Agbaje, 2007).Thomas et al. (1991) have shown that the aqueous extractof cotton seed meal contains substances that can rapidlyadversely affect the testicles, liver, kidney and muscles.

5. Conclusion

Plants with antimalarial effects are readily available in Lagos,Nigeria. Despite their wide range of adverse effects, theyare potential sources of new antimalarial treatments. Theirpresent use in raw forms should be guided by safety and effi-cacy data in humans. Lack of consensus, particularly amongthe THMPs, on the most effective plants, preparations, anddosages may limit the use of medicinal antimalarial plants.

Conflicts of interest statement

The authors have no conflict of interest to declare concerningthe medicinal plants reported in this paper.

Acknowledgement

The authors are grateful to the respondents, the Lagos stateTraditional Medicine Board, the Traditional Herbal MedicinePractitioners, and the Herb sellers Association in Lagos state,Nigeria.

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Appendix A. Supplementary data

Supplementary data associated with this article can be found,in the online version, at doi:10.1016/j.hermed.2014.08.001.

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