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Author’s Accepted Manuscript

Treatment of Malaria and Related Symptoms Using


Traditional Herbal Medicine in Ethiopia

Sultan Suleman, Takele Beyene Tufa, Dereje


Kebebe, Sileshi Belew, Yimer Mekonnen, Fanta
Gashe, Seid Musa, Evelien Wynendaele, Luc
Duchateau, Bart De Spiegeleer
www.elsevier.com/locate/jep

PII: S0378-8741(17)32299-7
DOI: https://doi.org/10.1016/j.jep.2017.10.034
Reference: JEP11089
To appear in: Journal of Ethnopharmacology
Received date: 20 June 2017
Revised date: 30 October 2017
Accepted date: 31 October 2017
Cite this article as: Sultan Suleman, Takele Beyene Tufa, Dereje Kebebe, Sileshi
Belew, Yimer Mekonnen, Fanta Gashe, Seid Musa, Evelien Wynendaele, Luc
Duchateau and Bart De Spiegeleer, Treatment of Malaria and Related Symptoms
Using Traditional Herbal Medicine in Ethiopia, Journal of Ethnopharmacology,
https://doi.org/10.1016/j.jep.2017.10.034
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Treatment of Malaria and Related Symptoms Using Traditional Herbal

Medicine in Ethiopia

Sultan Suleman1,2*, Takele Beyene Tufa1,2,3,4, Dereje Kebebe1,2, Sileshi Belew1,2,3, Yimer

Mekonnen1,2, Fanta Gashe2, Seid Musa2, Evelien Wynendaele3, Luc Duchateau5, Bart De

Spiegeleer3

Ref. No. 2017-001l


1
Jimma University Laboratory of Drug Quality (JuLaDQ), Jimma University, PO Box 378,

Jimma, Ethiopia.
2
School of Pharmacy, Jimma University, P.O.Box 378, Jimma, Ethiopia.
3
Drug Quality and Registration (DruQuaR) group, Faculty of Pharmaceutical Sciences, Ghent

University, Ottergemsesteenweg 460, B-9000 Ghent, Belgium.


4
College of Veterinary Medicine and Agriculture, Addis Ababa University, P.O.Box 34,

Bishoftu, Ethiopia.
5
Department of Comparative Physiology and Biometrics, Faculty of Veterinary Medicine,

Ghent University, Salisburylaan 133, B-9820 Merelbeke, Belgium.

*Corresponding author

E-mail addresses:
SS: sultan.suleman@ju.edu.et
TBT: takele.beyene@aau.edu.et
DK: dereje.kebebe@ju.edu.et
SB:sbphar2009@gmail.com
YM: yimer.mekonnen@ju.edu.et
FG:fantwark@gmail.com
SM:plss1176@gmail.com
EW: ejwynend.Wynendaele@UGent.be
LD: Luc.Duchateau@UGent.be
BDS: Bart.Despiegeleer@UGent.be

1
ABSTRACT
Ethnopharmacological relevance: Medicinal plants have always been an integral part of

different cultures in Ethiopia in the treatment of different illnesses including malaria and related

symptoms. However, due to lack of proper documentation, urbanization, drought, acculturation

and deforestation, there is an increased risk of losing this traditional knowledge. Hence, the use

of the indigenous knowledge should be well documented and validated for potential future use.

Aim of the study: To gather and document information on medicinal plants which are used in

the traditional treatment of malaria and related symptoms in Ethiopia.

Materials and Methods: First, an ethnomedicinal survey of plants was conducted in 17 districts

of Jimma zone, the Oromia national regional state of Ethiopia. Jimma zone is malarious and

rich in natural flora. A total of 115 traditional healers were interviewed using a semi-structured

questionnaire containing personal data of the respondents, and information on medicinal plants

used to treat malaria and related symptoms. In addition, a literature search using

Medline/PubMed, Google Scholar, ScienceDirect and HINARI was conducted on the

indigenous use, in-vitro/in-vivo anti-malarial activity reports, and the chemical characterization

of medicinal plants of Ethiopia used against malaria.

Results: From ethnomedicinal survey, a total of 28 species of plants used in the traditional

treatment of malaria and related symptoms in Jimma Zone were collected, identified and

documented. In addition, the literature search revealed that 124 medicinal plant species were

reported to be traditionally used in the treatment of malaria in Ethiopia. From both

ethnomedicinal survey and the literature search, Asteraceae and Fabaceae were the most

represented families and Allium sativum L., Carica papaya L., Vernonia amygdalina Del.,

Lepidium sativum L. and Croton macrostachyus Del. were the most frequently reported plant

species for their anti-malarial use. The dominant plant parts used in the preparation of remedies

were leaves. About 54% of the medicinal plants documented in the survey have been reported

2
as an anti-malarial plant in the literature search. Furthermore, the in-vitro and in-vivo anti-

plasmodial activity reports of extracts from some of plant species were found to support the

traditional claim of the documented plants. Moreover, literatures indicate that several secondary

metabolites isolated from certain plant species that are traditionally used for the treatment of

malaria and related symptoms in Ethiopia demonstrate strong anti-plasmodial activity.

Conclusions: The result of the current study showed that traditional knowledge is still playing

an important role in the management of malaria and related symptoms in Ethiopia. Allium

sativum L., Carica papaya L., Vernonia amygdalina Del., and Lepidium sativum L. are the

most commonly reported species as anti-malarial plants and the traditional claim of some

species was supported by known anti-plasmodial activity and bioactivity reports. The finding of

this study is important in the rational prioritization of plant species which are potentially used

for investigating new compounds, which could be efficacious for malaria treatment.

Keywords: Endemic plants; Ethiopia; Herbal-medicine; Malaria; Related symptoms;

Traditional treatment

1. INTRODUCTION
Malaria continues to have a devastating impact on public health. The WHO estimates that

212 million cases occurred globally in 2015, leading to 429 000 deaths, most of which were in

children aged under 5 years in Africa (WHO, 2016). Approximately, 68% of Ethiopia’s total

population live in malaria-endemic areas (Federal Ministry of Health of Ethiopia, 2000).

Malaria is among the ten top causes of morbidity and admission in Ethiopia (Federal Ministry

of Health of Ethiopia, 2015). Despite major progresses made to improve the health coverage of

the country, a wide range of differences in the coverage of services and distribution of health

facilities persists among regions as well as between urban and rural areas. The available option

3
for the population is, therefore, the use of traditional herbal medicines. Moreover, the

increasing global spread of drug resistance to most of the available and affordable anti-malarial

drugs is a major concern and requires innovative strategies to combat the disease. There is an

urgent need for new chemotherapeutic compounds and thus one of the possible sources for such

new treatments lies in the use of traditional herbal remedies (Bagavan et al., 2011).

Traditional medicines have been used to treat malaria for thousands of years and are the

source of the two main groups (artemisinin and quinine derivatives) of modern anti-malarial

drugs (Willcox and Bodeker, 2004).

The Ethiopian flora is rich with a lot of medicinal plants and for centuries indigenous

people have been using them for various physical and mental disorders and other diseases

(Debella, 2014). Malaria is one of the public health problem in Ethiopia and people living in

malaria endemic remote rural areas commonly use different medicinal plants for the treatment

of malaria. Despite the wide use of medicinal plants in the traditional health care, the

information has not been documented in a scientific way and there is an increased risk of losing

this traditional knowledge. Therefore, this study was conducted to gather and document

information on medicinal plants that are being used in the traditional treatment of malaria and

related symptoms in Ethiopia, which is useful in rational prioritization of plant species for

further investigation, and integrating these medicinal plants into the modern medicine through

pharmacological and chemical analysis of such traditional plants in Jimma areas.

2. METHODS

With the aim of gathering and documenting information on medicinal plants being used

in the traditional treatment of malaria and related symptoms in Ethiopia, the study involved an

ethnomedicinal survey and a systematic review.

4
2.1 Ethnomedicinal Survey

2.1.1 Study area

The ethnomedicinal survey of plants traditionally used in the treatment of malaria and

related symptoms was conducted in the 17 malarious districts of Jimma zone. Jimma zone was

purposively selected since almost all the districts are malarious and it is in the rich natural flora

of the southwest of the country. Due to high rainfall, all the districts of the zone are rich in

dense tropical forest vegetation.

Jimma zone is one of the 12 zones of Oromia regional state in southwest Ethiopia with

its capital, Jimma town (Figure 1). It is located 357 kms southwest of Addis Ababa. The zone
o o o o
extends between 7 13’- 8 56’ north latitudes and 35 49-38 38’ east longitudes. Jimma zone

generally lies between 1000 and 3500 meters above sea level. The annual rainfall lies between

1300 mm-2100 mm (Oromia Bureau of Finance and Economic Development, 2009).

Figure 1. Map of Jimma Zone, Ethiopia


2.1.2 Data collection

The ethnomedicinal survey was conducted from September to December 2013. With the

assistance of the local administrator, local people and field assistants, a total of 120 traditional

healers were initially identified in the zone and 115 of them became volunteers to be involved

5
in the study. The traditional healers were approached through community leaders and the

purpose and the benefits of the study were briefly explained to them. Using semi-structured

interview, the ethnomedicinal data were collected on knowledge of malaria and medicinal

plants used for the treatment of malaria and related symptoms, parts used, mode of

administration, growth habit, dosing methods, and season of collection.

2.1.3 Plant collection

At the end of the interview, the reported medicinal plants were collected from natural

vegetation or home garden with the help of the traditional healers. The collected plant

specimens were dried, identified and deposited at Jimma University, Biology department

herbarium. Identification was performed by using taxonomic keys and floras and by

comparison with the already identified herbarium specimen by the botanist of the department of

biology, Jimma University. The name of each plant species has been checked with

http://www.theplantlist.org.

2.1.4 Data management and analysis

The collected data were entered into SPSS version 16, analyzed and summarized using

simple descriptive statistics. Different indices were also used to summarize the results of the

questionnaire.

The frequency index (FI) corresponds to the percentage of informants that mentions the

use of the plant species for the management of malaria (Mahwasane et al., 2013) and is given


by  = 
× !! where FC the number of informants who mentioned the use of the species

for the treatment of malaria, and N the total number of informants.

2.2 Literature Search

2.2.1 Study design and data sources

A literature review was carried out through a computer search of the databases

Medline/PubMed, Google Scholar, ScienceDirect and HINARI using a search strategy with

6
keywords ethnopharmacological survey, ethnomedicine, ethnobotany, traditional medicine,

herbal medicines, medicinal plants, treatment of malaria and Ethiopia. Additionally, the grey

literature was also searched.

Potentially relevant original articles were selected by the following inclusion criteria:

(1) Describe at least one species of medicinal plants used in the treatment of malaria and related

symptoms, (2) Describe the medical uses, parts used, habitat, methods of preparation and route

of administration of medicinal plants, (3) Studies conducted in Ethiopia, and (4) Published in

English language.

2.2.2 Selection of studies

The selection of the articles was done in three steps. In the first step, the relevance of the

studies was checked based on their title. Some articles could be excluded just based on the title.

In the second step, abstracts were evaluated and based on that, the articles were excluded if

they did not match to the inclusion criteria. For the remaining publications, the whole content

of the articles was accessed (Figure 2). The screening process was performed by two

independent researchers (DK and SB).

Articles identified through database


searching (n=1283)

Reasons for exclusion (n=1227)


· Unrelated to the objective of the review
· Duplications
· Study conducted outside of Ethiopia

Articles remained for detail


screening (n=56)
Additional articles
identified through other
sources (n=13)

Full text articles screened for


eligibility (n=69)

Articles excluded (n=17)


· Ethnoveterinary study
· No plants reported for
malaria
Articles included in the
systematic review
(n=52)
7
Figure 2. Flow diagram showing the selection process of studies included in the literature
search.

2.2.3 Data extraction and analysis

The terms: title, authors, year of publication, study design, study site (region), sample

size, type of respondents, the number of plant species used in the treatment of malaria, habitat,

parts used, and the method of preparation were extracted from the eligible published

papers/articles.

2.3 Anti-plasmodial Activity Report of Extracts and Isolated Compounds

Previous reports on the anti-plasmodial activity of extracts and isolated compounds from

the plant species identified in this study were searched in scientific databases using the

‘scientific name’ of the plant, ‘anti-malarial’ and ‘compound’ as search terms. Activities of

extracts were classified as follows: high or pronounced activity (IC50 ≤ 5 μg/ml); good or

promising activity (5 μg/ml < IC50 ≤ 15 μg/ml); moderate activity (15 μg/ml < IC50 ≤ 50 μg/ml)

and weak activity (50 μg/ml < IC50 ≤ 100 μg/ml). A pure compound is defined as highly active

when it’s IC50 ≤ 1 μg/ml (Jonville et al., 2008; Memvanga et al., 2015).

2.4 Ethical considerations

This study was reviewed and approved by the Ethical Clearance Committee (JURO/04/2013) of

the Jimma University. Verbal informed consent was obtained from all respondents who

participated in the study after explaining the purpose and objectives of the study in the local

language. Participation in the study was voluntary and confidentiality of the information was

8
assured both during and after data collection. The respondents were informed about their right

either not to participate, not to answer any question or all the questions.

3. RESULTS

3.1 Ethnomedicinal Survey

3.1.1 Sociodemographic characteristics of the respondents

A total of 115 traditional healers (98 male and 17 female) from the 17 malarious

districts of Jimma zone were involved in the ethnomedicinal survey. Twenty-one of them were

not willing to give sufficient information about the name of the plant they use to treat illnesses

because they had been told by their parents not to tell the information except to their family

members. The study revealed that men have more involvement in traditional medical practice

than women, which could be due to the fact that parents usually prefer boys in the transfer of

the indigenous knowledge. The study also showed that most of the traditional medical

practitioners (83%) were ≥ 40 years old. Most of the healers (63.7%) reported that they

acquired the knowledge from their family; while the remaining proportion gained the

knowledge through other means such as from friends, local elders, Quran and neighbour.

The term ‘Busaa’ (in Afaan oromoo) or ‘Woba’ (in Amharic) was used to denote

malaria and related symptoms in local languages. The healers reported to use different signs

and symptoms, namely headache (103), fever (97), vomiting (68), joint pain (65), shivering

(64), chills (53), loss of appetite (51) and other (8) to diagnose malaria. Moreover, the

traditional healers reported that they conventionally define malaria and related illnesses in

terms of fever, chilling, and/or headache.

From the traditional healers interviewed, 78% had an experience of treating patients

with malaria and related symptoms using medicinal plants. Most of the respondents (78.3%)

had more than 10 years of experience as a traditional healer.

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3.1.2 Medicinal plants, parts used and habit

A total of 28 medicinal plant species belonging to 24 families were reported by the

traditional healers as being used for the treatment of malaria and related symptoms in Jimma

zone (Table 1). Most of the medicinal plants used were trees (36%), followed by shrubs (32%).

The frequency index result showed that Allium sativum L. and Carica papaya L. showed the

highest incidence of use (Table 1), claimed by 31 (32.9%) and 27 (28.7%) traditional healers,

respectively. Lepidium sativum L., Brassica nigra (L.) K.Koch and Vernonia amygdalina Del.

were also reported by 12 (12.8 %), 9 (9.6 %), and 7 (7.4 %) respondents, respectively.

The plant parts most frequently used were leaves. Most of the plants were collected

from wild. Informants in the study area confirmed that most of medicinal plants can be

collected in all seasons (57.1%), and at any time (85.7%) of the day. Almost all of the herbal

preparations used for the treatment of malaria and related symptoms in this study area were

taken by oral route. Herbal medicines were commonly prepared using water and honey as

excipients, but occasionally remedies were prepared with other excipients including milk,

coffee, butter, table salt, sugar and tea. Some of the remedies were used directly without using

excipients.

10
Table 1. Plant species used in the treatment of malaria and related symptoms by traditional healers (n = 94) of Jimma Zone

Vernacular Name Scientific Name Family Voucher Life form Part(s) used Site of growth Mode of use Dosage Route of No of
No Administration informants
O
Qulubi adi Allium sativum L. Amaryllidaceae DK020 Herb Root Domestic Fresh /Dried Juice Oral 31
A
Papaya Carica papaya L. Caricaceae DK010 Tree Leaf / Fruit / Root Domestic Fresh /Dried Powder Oral 27
/Decoction
ShinfaO Lepidium sativum L. Brassicaceae DK027 Herb Seed Domestic Fresh /Dried Juice Oral 12
SenafichA Brassica nigra (L.) K. Koch Brassicaceae DK024 Herb Seed Domestic Fresh /Dried Powder Oral /Topical 9
GirawaA Vernonia amygdalina Del. Asteraceae DK005 Shrub Leaf / Flower Wild Fresh Juice Oral 7
Tikur asmudA Nigella sativa L. Ranunculacae DK014 Herb Seed Domestic Fresh /Dried Powder Oral 7
DamakaseO Ocimum lamiifolium Hochst. ex Benth Lamiaceae DK002 Shrub Leaf / Flower Wild Fresh /Dried Tea /Powder Oral 6
MakanisaO Croton macrostachyus Hochst. ex Del. Euphorbiaceae DK009 Tree Leaf Wild Fresh Powder Oral /Inhalation 6
AgamA Carissa spinarum L. Apocynaceae DK011 Shrub Leaf/ Root Wild Fresh /Dried Tea Oral 3
BarbareA Capsicum frutescens L. Solanaceae DK003 Herb Fruit Domestic Fresh /Dried Juice Oral 2
Barzafi adiiO Eucalyptus globulus Labill. Myrtaceae DK021 Tree Fruit Domestic Fresh Juice Oral 2
HudhaO Ximenia americana L. Olacaceae DK007 Tree Stem Wild Fresh /Dried Juice Oral 2
LomiA Citrus limon (L.) Osbeck Rutaceae DK012 Tree Fruit Wild Fresh Powder Oral 2
ShiferawA Moringaceae DK015 Tree Leaf Wild Fresh /Dried Juice Oral 2
Moringa stenopetala (Baker f.) Cufod.
AnunnuO Ekebergia capensis Sparrm. Meliaceae DK008 Tree Root Wild Dried Powder Oral 1
AzamirA Bersama abyssinica Fresen. Francoaceae DK017 Tree Leaf Wild Dried Powder Oral 1
DhumugaO Justicia schimperiana (Hochst. ex Nees) T. Anderson Acanthaceae DK013 Shrub Leaf Wild Fresh Juice Oral 1
EmbuayA Solanum incanum L. Solanaceae DK018 Shrub Seed Wild Dried O Oral /Inhalation 1
EnjoriA Rubus steudneri Shweinf. Rosaceae DK001 Shrub Root Wild Dried Powder Oral 1
Jinjible A Zingiber officinale Roscoe Zingiberaceae DK006 Herb Root Domestic Dried Powder Oral 1
QommonyoO Brucea antidysentrica J.F.Mill. Simaroubaceae DK019 Shrub Bark Wild Dried Powder Oral 1
QurquraO Ziziphus mauritiana Lam. Rhamnaceae DK016 Tree Leaf Wild Fresh /Dried Juice Oral 1
SanamakiiO Senna didymebotrya (Fresen.) H.S.Irwin & Barneby Fabaceae DK022 Shrub Leaf Wild Dried Tea Oral 1
SunqooO Trigonella foenum-graecum L. Fabaceae DK023 Herb Seed Domestic Fresh /Dried Juice Oral 1
TelbaA/O Linum usitatissimum L. Linaceae DK026 Herb Seed Domestic Fresh /Dried Juice Oral 1
WanzaA Cordia africana Lam. Boraginaceae DK028 Tree Leaf Wild Dried Powder Oral /Topical 1
SoyyomaO Vernonia species* Asteraceae DK025 Shrub Leaf Wild Fresh Juice Oral 1
Ye medir embuayA Cucumis prophetarum L. Cucurbitaceae DK004 Climber Fruit/ Root Wild Dried Powder Oral 1
Vernacular name: A = Amharic, O = Afaan Oromoo
*the species could not be identified

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3.2 Literature Search

In this literature search, a total of 124 medicinal plant species belonging to 55 families

and 99 genera were reported to be used in the treatment of malaria and related symptoms in

Ethiopia (Table 2). The number of cited anti-malarial plant species, which were originated from

surveys in all regional states of Ethiopia except Gambella (Appendix 1), varied from study to

study.

The most frequently cited plant species by the studies were Allium sativum L., Carica

papaya L., Vernonia amygdalina Del., Lepidium sativum L., and Croton macrostachyus Del.

and Adhatoda schimperiana Hochst.. In this literature review, only two species of plants which

are endemic to Ethiopia (Leucas stachydiformis Hochst. ex Benth. and Aloe pirottae A. Berger)

were reported to be used in the treatment of malaria (Etana, 2010; Belayneh and Bussa, 2014).

People employed variety of methods to prepare remedies in single and in multiple

preparations. The modes of preparation include crushing, boiling and squeezing. Certain

additives are frequently used to improve the acceptability of some remedies that are taken

orally. This could be water, honey, sugar, milk, local alcohol and butter.

12
Table 2. Summary of medicinal plants identified from the literature search
Number
Plant species Family Local name Life form Parts used References
of citation Number of
Plant species Family Local name Life form Parts used References
citation

Acacia mellifera (Vahl) Benth. Fabaceae Aygae (Ka) Tree Leaf 1 Teklehaymanot and Giday, 2010
Acacia robusta Burch. Fabaceae Wangeyo (Or) Tree Root 1 Belayneh et al., 2012
Acacia seyal Delile. Fabaceae Tundukiyac (Ko) Tree Gum-bark 1 Mesfin et al., 2014
Acalypha indica L. Euphorbiaceae Habrid (So) Herb Aerial part 1 Mesfin et al., 2012
Acalypha species Euphorbiaceae Subaci (Af) Herb Whole plant 1 Seifu et al., 2006
Acanthus polystachius Delile. Acanthaceae Dendero (Am) Herb Root 1 Giday et al., 2007
Acokanthera schimperi (A. DC.) Belayneh et al., 2012; Mesfin et al., 2012; Belayneh and
Apocynaceae Kararo (Or) Shrub Leaf, Stem 3
Schweinf. Bussa, 2014
Justicia schimperiana (Hochst. ex Nees) T.
Sensel (Am), Gedif and Hahn, 2002; Seid and Tsegay, 2011; Zerabruk
Anderson Acanthaceae Herb Leaf 5
Dhumuga (Or) and Yirga, 2012; Regassa, 2013; Gebeyehu, 2011

Afrocarpus gracilior (Pilg.) C.N.Page Podocarpaceae Zigba (Am) Tree Leaf 1 Dori et al., 2012

Ajuga remota Benth. Lamiaceae Armagusa (Or) Herb Leaf 1 Suleman et al., 2009
Albizia amara (Roxb.) B.Boivin Fabaceae Ondoddee (Or) Tree Bark 1 Mesfin et al., 2014
Allium cepa L. Amaryllidaceae Key shinkurt (Am) Herb Bark 2 Gabriel and Guji, 2014; Getaneh et al., 2014
Gedif and Hahn, 2002; Tadesse et al., 2005; Mesfin et al.,
2009; Amenu, 2007; Gashe and Worku, 2007;
Teklehaymanot et al., 2007; Suleman et al., 2009; Etana,
Qulubi adii (Or), 2010; Gebrehiwot, 2010; Yirga, 2010b, 2010c; Beyene,
Allium sativum L. Amaryllidaceae Herb Bark 22
Nech shinkurt (Am) 2011; Guji et al., 2011; Seid and Tsegay, 2011; Zerabruk et
al., 2012; Lulekal et al., 2013; Megersa et al., 2013;
Regassa, 2013; Teklay et al., 2013; Abera, 2014; Gabriel
and Guji, 2014; Mesfin et al., 2014
Aloe macrocarpa Tod. Asphodelaceae Algae (Sd) Shrub Leaf, Latex 1 Regassa, 2013
Aloe megalacantha Baker. Asphodelaceae Ere (T) Shrub Root 1 Teklay et al., 2013
Table 2. (continued)

13
Leaf,
Aloe pirottae A. Berger Asphodelaceae Hargeysa (Or) Shrub 1 Belayneh and Bussa, 2014
Latex
Leaf, Seifu et al., 2006; Giday et al., 2007; Mesfin et
Aloe sp. Asphodelaceae Eret (Am) Shrub 3
Latex al., 2012
Bark,
Andrachne aspera Spreng. Euphorbiaceae unknown Herb 1 Hunde et al., 2006
Root
Anethum graveolens L. Apiaceae Karmn (So) Shrub Leaf, Root 1 Mesfin et al., 2012
Anogeissus leiocarpa (DC.) Guill. &
Combretaceae Hanse (T) Tree Leaf, Bark 1 Zenebe et al., 2012
Perr.
Artemisia abyssinica Sch.Bip.ex Herb
A.Rich. Asteraceae Sunadohayiso (Sd) Leaf 1 Beyene, 2011

Artemisia afra Jacq. ex Willd. Asteraceae Chikun (Am) Herb Leaf 2 Mesfin et al., 2009; Bekele and Reddy , 2015
Artemisia rehan Choiv. Asteraceae Nechryan (Am) Herb Leaf 1 Gedif and Hahn, 2002
Asparagus africanus Lam. Liliaceae Sariitii, Ged-ay (T) Shrub Leaf 2 Mesfin et al., 2012
Tree Giday et al., 2007; Dori et al., 2012; Mesfin et
Azadirachta indica A. Juss. Meliaceae Kinina (Or), Neem Leaf 4
al., 2012; Belayneh and Bussa, 2014
Balanites aegyptiaca (L.) Del. Zygophyllaceae Bedeno (Or), Tree Leaf, Root 1 Belayneh et al., 2012
Balanites rotundifolia (Tiegh.) Blatt. Zygophyllaceae Qaalayto (Af) Shrub Leaf 2 Seifu et al., 2006; Mesfin et al., 2012
Tree Whole
Bersama abyssinica Fresen. Francoaceae Lolchiisaa (Or) 1 Abera, 2003
part
Boscia coriacea Pax Capparaceae Shodo (Ka) Tree Root 1 Teklehaymanot and Giday, 2010
Brassica carinata A.Braun Tree
Brassicaceae Shaana (Sd) Seed 1 Regassa, 2013
Brassica nigra (L.) K.Koch Brassicaceae Senaficha (Or) Herb Seed 1 Guji et al., 2011
Stem, Abera, 2003; Suleman et al., 2009; Suleman
Brucea antidysentrica J.F. Miller Simaroubaceae Kumegno, Aballo (Or) Shrub 3
Bark and Alemuet al., 2012
Kamppaaraa, Adano
Buddleja polystachya Fresen. Scrophulariaceae Shrub Leaf 2 Bekalo et al., 2009; Gebrehiwot, 2010
(Kon)
Giday et al., 2007; Regassa, 2013; Gebeyehu,
Calpurnia aurea (Ait.) Benth Fabaceae Digita (Am) Tree Leaf 3
2011
Capparis tomentosa Lam. Capparaceae Gumero (Am) Shrub Root 1 Teklehaymanot et al., 2007
Giday et al., 2007; Chekole et al., 2015;
Capsicum annuum L. Solanaceae Mitmita (Am) Herb Fruit 3
Kidane et al., 2014

Table 2. (continued)

Plant species Family Local name Life Parts used Number of References

14
form citation
Tadesse et al., 2005; Amenu, 2007; Giday et al.,
2007; Teklehaymanot and Giday, 2007; Bekalo et al.,
2009; Suleman et al., 2009; Etana, 2010; Giday et al.,
Carica papaya L. Caricaceae Papaya (Am) Tree Leaf, Root 16
2010; Seid and Tsegay, 2011; Beyene, 2011;
Suleman et al., 2012; Megersa et al., 2013; Regassa,
2013; Abera, 2014; Chekole et al., 2015
Carissa spinarum L. Apocynaceae Agamsa (Or) Shrub Root 1 Gebrehiwot, 2010

Cicer arietinum L. Fabaceae Shinbira (Am) Herb Seed 1 Chekole et al., 2015
Menispermacea Guji et al., 2011
Cissampelos mucronata A. Rich Jebcha (G) Climber Root 1
e
Menispermacea Teklehaymanot and Giday, 2007
Cissampelos pareira L. Gud (Ka) Climber Root 1
e
Root, Mesfin et al., 2012
Cissus rotundifolia Vahl Vitaceae Armon (So) Clilmber 1
Root-Bark
Clerodendrum myricoides (Hochst.) Wondimu et al., 2007; Gebrehiwot, 2010; Gebeyehu,
Lamiaceae Maraasisaa (Or) Shrub Root 3 2011
R.Br. ex Vatke
Clutia abyssinica Jaub. & Spach Euphorbiaceae unkown Shrub Leaf, Fruit 1 Seid and Tsegay, 2011

Coffea arabica L. Rubiaceae Bunna (Or) Shrub Root 1 Beyene, 2011

Combretum molle R.Br. ex G.Don Combretaceae Agalo (Am) Shrub Leaf, Bark 1 Mesfin et al., 2014
Whole Mesfin et al., 2014
Commiphora africana (A.Rich.) Endl. Burseraceae Unknown Shrub 1
part
Conyza pyrrhopappa Sch.Bip. ex A.Rich. Asteraceae Dadaho (So) Tree Leaf 1 Mesfin et al., 2012
Root, Mesfin et al., 2014
Cordia africana Lam. Boraginaceae Wanza (Am) Shrub 1
Bark
Crabbea velutina S.Moore Leaf, Dori et al., 2012
Acanthaceae Malgissa (Ks) Shrub 1
Stem
Gedif and Hahn, 2002; Tadesse et al., 2005; Mesfin
et al., 2009; Giday et al., 2007; Suleman et al., 2009;
Croton macrostachyus Hochst. ex Root,
Euphorbiaceae Makanisaa (Or) Tree 12 Etana, 2010; Suleman et al., 2012; Teklay et al., 2013;
Delile. Bark
Abera, 2014; Gebeyehu, 2011; Mesfin et al., 2014;
Bekele and Reddy, 2015
Table 2. (continued)

Number of
Plant species Family Local name Life form Parts used References
citation
Cucumis ficifolius A. Rich. Cucurbitaceae Anundemerit (So) Herb Whole plant 1 Mesfin et al., 2012

15
Cucurbita spp. Cucurbitaceae Gim Hareg /Dursht (Am) Climber Root 1 Teklehaymanot et al., 2007
Datura stramonium L. Solanaceae Manji (Or) Herb Fruit 1 Amenu, 2007
Giday et al., 2007; Belayneh et al., 2012;
Dodonaea angustifolia L.f. Sapindaceae Kitkita (Am) Tree Seed, Leaf, Fruit 4
Teklay et al., 2013; Gebeyehu, 2011
Dodonaea viscosa (L.) Jacq. Sapindaceae unknown Shrub Fruit 1 Yirga, 2010a

Droguetia iners (Forssk.) Schweinf. Urticaceae Yewoba medihanit (Am) Herb Leaf 1 Tolossa et al., 2013
Echinops amplexicaulis Oliv. Asteraceae Joga (G) Herb Root 1 Guji et al., 2011

Echinops hoehnelii Schweinf. Asteraceae Qeber (SK) Herb Root 1 Getaneh et al., 2014

Embelia schimperi Vatke k'amjach (Me) Shrub Fruit 1 Abbink, 1993


Primulaceae
Eucalyptus globulus Labill. Myrtaceae Bahirzaf (Am) Tree Leaf 2 Regassa, 2013; Etana, 2010

Euclea divinorum Hiern Ebenaceae Baarzaafiiadii (Or) Shrub Root 1 Dori et al., 2012
Euphorbia abyssinica J.F.Gmel. Euphorbiaceae Kulkual (Am) Tree Nectar 2 Belayneh et al., 2012

Ficus platyphylla Delile. Moraceae Hadawa (Ks) Tree Bark 1 Dori et al., 2012
Ficus sur Forssk. Moraceae Odako (Sd) Tree Fruit 1 Beyene, 2011

Foeniculum vulgare Miller Apiaceae Kelela (Or) Herb Root 2 Gedif and Hahn, 2002; Mesfin et al., 2012

Gardenia lutea Fresen. Rubiaceae Gambelo (Sh) Tree Root 1 Giday et al., 2009b
Gardenia ternifolia Schumach. & Tree Leaf, Stem, Abbink, 1993; Yineger et al., 2008; Giday
Rubiaceae Gembala (Ma) 4
Thonn. Bark et al., 2009b; Kidane et al., 2014
Gnidia involucrata Steud. ex A.Rich. Thymelaeaceae Yezinjero telba (Am) Herb Leaf 1 Gebeyehu, 2011
Halothamnus somalensis (N.E.Br.)
Amaranthaceae Mirow (So) Shrub Root 1 Mesfin et al., 2012
Botsch.
Harrisonia abyssinica Oliv. Rutaceae Moy Moy (KW) Tree Root, Bark 1 Teklehaymanot and Giday, 2010
Hydnora johannis Becc. Aristolochiaceae Liko (So) Stem Root 1 Mesfin et al., 2012
Table 2. (continued)

Number
Life
Plant species Family Local name Parts used of References
form
citation
Hypoestes forsskaolii (Vahl) R.Br. Acanthaceae Kuneyta (Kon) Herb Leaf, Root 1 Dori et al., 2012

16
Indigofera articulata Gouan Fabaceae Gabalday (So) Shrub Root 1 Mesfin et al., 2012

Indigofera coerulea Roxb. Fabaceae Gabalday(So) Herb Leaf 1 Mesfin et al., 2012

Indigofera Sp. Fabaceae Wende Ayrowagit (Am) Herb * 1 Seifu et al., 2006

Indigofera spicata Forssk. Fabaceae Shersherit, Am) Herb Root 1 Giday et al., 2009b

Ipomoea kituiensis Vatke Convolvulaceae Laalata (Ko) Climber Leaf 1 Mesfin et al., 2014

Jatropha curcas L. Euphorbiaceae Habet-muluk (So) Shrub Stem 1 Mesfin et al., 2012

Lagenaria siceraria (Molina) Standl. Cucurbitaceae Buqqe hadhaa (Or) Climber Fruit 1 Amenu, 2007

Lantana trifolia L. Verbenaceae Yewoba medihanit (Am) Shrub Root 1 Tolossa et al., 2013
Root, Root
Lawsonia inermis L. Lythraceae Elan (So) Tree 1 Mesfin et al., 2012
stem
Hunde et al., 2006; Mesfin et al., 2009; Amenu,
2007; Ragunathan and Abay, 2009; Etana, 2010;
Guji et al., 2011; Dori et al., 2012; Suleman et al.,
Lepidium sativum L. Brassicaceae Shinfa Herb Seed 13
2012; Megersa et al., 2013; Abera, 2014; Bekele et
al., 2015; Gabriel and Guji, 2014; Mesfin et al.,
2014
Root, Root-
Leptadenia hastata (Pers.) Decne. Apocynaceae Mesker (So) Climber 1 Mesfin et al., 2012
stem
Leucas stachydiformis (Hochst. ex
Lamiaceae Qumudu (Or) Herb Whole plant 1 Etana, 2010
Benth.)
Lobelia sp. Campanulaceae Jibira (Am) Shrub Root 1 Giday et al., 2007

Lycium Shrubawii Roem and Schult Solanaceae Hedalusayto (Af) Shrub Root 1 Seifu et al., 2006

Lysimachia ruhmeriana Vatke Primulaceae Corqqaa Herb Root 1 Bekalo et al., 2009
Maerua oblongifolia (Forssk.) A.Rich.
Capparaceae Ja’a (So) Shrub Leaf 1 Mesfin et al., 2012

17
Table 2. (continued)

Number
Life
Plant species Family Local name Parts used of References
form
citation
Flatie et al., 2009; Etana, 2010; Beyene, 2011;
Melia azedarach L. Meliaceae Almim, kinini, niim Tree Leaf, Root 4
Regassa, 2013
Mentha spicata L. Lamiaceae Nana (So) Herb Aerial part 1 Mesfin et al., 2012
Moringa oleifera Lam. Moringaceae Birbira (Or) Tree Leaf 2 Suleman et al., 2009; Seifu et al., 2006
Tree Bekalo et al., 2009; Dori et al., 2012; Regassa,
Moringa stenopetala (Baker f.) Moringaceae Shiferaw (Am) Root, Leaf 4
2013; Kidane et al., 2014
Myrsine africana L. Primulaceae Kechemo (Or) Shrub Leaf 1 Suleman et al., 2009
Nigella sativa L. Ranunculaceae Tikurazmud (Am) Herb Seed 1 Suleman et al., 2009
Ocimum gratissimum L. Lamiaceae Damakasse (Am, Or) Herb Leaf 1 Suleman et al., 2009
Ocimum lamiifolium Hochst. ex Benth Lamiaceae Damakesse (Am, Or) Shrub Leaf 3 Seid and Tsegay, 2011; Suleman et al., 2009
Ocimum spicatum Deflers Lamiaceae Shero (So) Herb Leaf 1 Mesfin et al., 2012
Olea africana Mill. Oleaceae k'erach (Me) Tree Bark 1 Abbink, 1993
Tree Abbink, 2002; Suleman et al., 2009; Teklay et
Olea europaea L. Oleaceae Weyra (Am) Bark 3
al., 2013
Osyris quadripartita Salzm. ex Decne Santalaceae Wato (Or) Shrub Leaf, Root 1 Belayneh et al., 2012
Otostegia integrifolia Benth. Lamiaceae Tinjut (Am) Shrub Leaf 2 Giday et al., 2007; Teklehaymanot et al., 2007
Not
Phyllanthus maderaspatensis L. Phyllanthaceae unknown Herb 1 Hunde et al., 2006
mentioned
Mesfin et al., 2009; Gebrehiwot, 2010; Chekole
Phytolacca dodecandra L'Hér. Phytolaccaceae Indode (Am) Shrub Leaf, Root 4
et al., 2015; Bekele and Reddy, 2015
Giday et al., 2007; Teklehaymanot and Giday,
Plumbago zeylanica L. Plumbaginaceae Warwaro (Ka) Herb Root 2
2010
Yewoba medihanit
Premna oligotricha Baker Lamiaceae Shrub Leaf 1 Tolossa et al., 2013
(Am)
Prunus persica (L.) Batsch Rosaceae Kok (Am) Tree Seed 1 Giday et al., 2007
Pupalia micrantha Hauman Amaranthaceae Mara’abis (So) Shrub Root 1 Mesfin et al., 2012)
Rhus natalensis Bernh. ex C. Krauss Anacardiaceae unknown Shrub Leaf 1 Mesfin et al., 2014
Ruta chalepensis L. Rutaceae Tenadam (Am) Herb Leaf 2 Amenu, 2007; Mesfin et al., 2014
Salsola somalensis N.E. Br. Amaranthaceae Korsaduma (Or) Shrub Leaf 1 Suleman et al., 2009

18
Table 2. (continued)

Parts Number of
Plant species Family Local name Life form References
used citation
Seifu et al., 2006; Teklehaymanot, 2010; Mesfin et
Salvadora persica L. Salvadoraceae Qadayto (Af) Shrub Root 3
al., 2012
Schinus molle L. Sapindaceae Qundo-berbere (Am) Tree Seed 1 Giday et al., 2007
Herb
Senna italica Mill. Fabaceae Sete Ayrowagit (Am) Leaf 2 Seifu et al., 2006; Yirga, 2010b
Silene macrosolen Steud. ex A. Rich. Herb
Caryophyllaceae Saerosaero (T) Root 1 Teklay et al., 2013
Tree
Syzygium guineense (Willd.) DC. Myrtaceae Duwancho (Ko) Leaf 1 Mesfin et al., 2014
Tree Flatie et al., 2009; Belayneh et al., 2012; Mesfin et
Tamarindus indica L. Fabaceae Roka (Or, S) Seed 3
al., 2012
Turraea mombassana C. DC. Meliaceae Pitercama (Ko) Shrub Root 1 Dori et al., 2012
Zebko (Ka),
Uvaria leptocladon Oliv. Annonaceae Tree Root 1 Teklehaymanot and Giday, 2010
Chochum (Kw)
Gedif and Hahn, 2002; Hunde et al., 2006; Mesfin et
al., 2009; Amenu, 2007; Lulekal et al., 2008; Etana,
Vernonia amygdalina Del. Asteraceae Ebicha (Or) Shrub Leaf 14 2010; Beyene, 2011; Dori et al., 2012; Megersa et
al., 2013; Regassa, 2013; Abera, 2014; Kidane et al.,
2014; Mesfin et al., 2014
Vernonia sp. Asteraceae Heten (Be) Shrub Leaf 1 Flatie et al., 2009
Withania somnifera (L.) Dunal Gizawa (Am), Gedif and Hahn, 2002; Dori et al., 2012; Mesfin et
Solanaceae Shrub Leaf 4
Kumo (Or) al., 2012; Abera, 2014
Zaleya pentandra (L.) C.Jeffrey Whole
Aizoaceae Abuuri (Af) Herb 1 Seifu et al., 2006
plant
Zehneria scabra Sond. Cucurbitaceae Areg-resa (Am) Climber Root 2 Giday et al., 2007; Getaneh et al., 2014

Local name: Af - Afar; Am - Amharic, Be - Berta; G - Gumz; Ka - Kara; Ko - Koorete; Kon - Konso; Kw - Kwego; Ma - Maalee, Me - Me’en; Or - Afan Oromo; Sh - Shinasha, Sd - Sidama;
Sk - Skeko; So - Somali; T - Tigray.

19
3.3 Comparative analysis of the survey with the literature search

The uses of medicinal plants documented in the ethnomedicinal survey of plants used for

the treatment of malaria and related symptoms were compared with the previous

ethnomedicinal studies from different parts of Ethiopia. The comparison showed that 54% of

medicinal plant documented in the survey has been reported previously as an antimalarial plant

in literature search. A high degree of similarity was found with the studies conducted in the

Goma district of the Jimma zone (6 plants overlap), Hawassa city, Southern Ethiopia (6 plants

overlap) and Gimbi district, Southwest Ethiopia (5 plants overlap).

The similarities between the survey and literature search with respect to the most

frequently cited families, species and parts of the plants used showed that Asteraceae and

Fabaceae are the dominantly represented families. Allium sativum L., Carica papaya L.,

Vernonia amygdalina Del., and Lepidium sativum L. are the top four frequently reported plant

species in both survey and literature search.

In the ethnomedicinal field survey, 13 plant species that were not reported as anti-malarial

plants in literature search were identified. These included Ekebergia capensis Sparrm,

Capsicum frutescens L., Solanum incanum L., Ximenia americana L., Rubus steudneri

Shweinf., Zingiber officinale Roscoe., Citrus limon L., Ziziphus mauritiana Lam., Senna

didymebotrya Fresen, Trigonella foenum-graceum L., Linum usitatissimum L., Vernonia spp

and Cucumis prophetarum L.

3.4 Anti-plasmodial Activities Reports of the Plants Identified/Documented in This Study

The literature search of anti-malarial activity reports of plant species documented from

ethnomedicinal surveys and literature search were performed. According to this review, of the

137-plant species identified/documented in this study, the in-vitro and in-vivo anti-plasmodial

activity were reported for 40 and 27 plant species, respectively. Most of the bioactivity studies

20
focused on crude extracts and fractions. The anti-plasmodial activity reports of the plant species

are summarized in Table 3 and 4, and discussed below.

3.4.1 In-vitro anti-plasmodial activity reports

Most of in-vitro anti-plasmodial testing was based on the [³H]-hypoxanthine

incorporation, and few of the studies used pLDH (Plasmodium lactate dehydrogenase) method

and microscopic method to measure the level of inhibition (Table 3). The anti-plasmodial

activity was assessed on different P. falciparum laboratory strains such as, the chloroquine-

sensitive (D6, D10, 3D7, NF54, FCA-20/Eth) and chloroquine-resistant (W2 and K1 strains).

The in-vitro anti-malarial activity ranges from 0.38 to 100 μg/ml. Among the plants which the

in-vitro activities were reported, 11 and 12 of them have shown the pronounced (IC50 ≤ 5μg/ml)

and promising (5 μg/ml < IC50 ≤ 15 μg/ml) anti-malarial activities respectively (Table 3).

3.4.2 In-vivo anti-plasmodial activity reports

Some crude extracts and fractions from Ethiopian medicinal plants have been evaluated

for in-vivo activity against Plasmodium berghei, ANKA (Table 4). The high activities

demonstrated by these plants render them good candidates for the identification and isolation of

anti-malarial compounds that could serve as a backbone for new drug development.

21
Table 3. In-vitro anti-plasmodial activity reports (n = 21) of medicinal plants used in the treatment of malaria and related symptoms in Ethiopia
Family Species Parts used Solvent Anti-malarial activity IC50 in Method References
µg/ml(a) or µM(b) and strain
Anacardiaceae Rhus natalensis Bernh Leaf H2O 23.8a (D6), 48.3a(W2) [3H]-Hypoxanthine Muthaura et al., 2015
a 3
Asteraceae Artemisia afra Jacq. ex Willd. Aerial part EtOH 7.0 (FCA-2/Eth) [ H]-Hypoxanthine Kassa et al., 1998
Leaf DCM 5.0 a(D10) pLDH Clarkison et al., 2004
Artemisia rehan Choiv. Aerial part EtOH 14.0 a(FCA-2/Eth) [3H]-Hypoxanthine Kassa et al., 1998
Vernonia amygdalina Delile Leaf EtOH 9.7a Microscopy Tona et al., 2004
Leaf PET 2.5a Microscopy Tona et al., 2004
Leaf IOH 2.7a Microscopy Tona et al., 2004
Boraginaceae Cordia africana Lam. Stem bark MeOH 25a(W2) [3H]-Hypoxanthine Muthaura et al., 2015
Brassicaceae Lepidium sativum L. Seed EtOH No effect(FCA-2/Eth) [3H]-Hypoxanthine Kassa et al., 1998
Burseraceae Commiphora africana (A.Rich.) Endl. Stem bark MeOH 10.2a(D6), 9.6 a (W2) [3H]-Hypoxanthine Muthaura et al., 2015
Capparaceae Capparis tomentosa Lam. Leaf DCM 65a(D10) pLDH Clarkson et al., 2004
Root DCM 38 a(D10) pLDH Clarkson et al., 2004
Caricaceae Carica papaya L. Leaf EtOH 18a(D6), 23a(W2) Microscopy Kovendan et al., 2012
Combretaceae Combretum molle R.Br Stem bark Acetone 38.17b(3D7) [3H]-Hypoxanthine Asres et al., 2001
Cucurbitaceae Zehneria scabra (L.f.) Sond. Whole plant DCM:MeOH 5.6a(D10) pLDH Clarkson et al., 2004
Euphorbiaceae Clutia abyssinica Jaub. & Spach Leaf MeOH 7.8a(D6), 11.3a(W2) [3H]-Hypoxanthine Muthaura et al., 2015
H2O 65.2a(D6), 100 a(W2) [3H]-Hypoxanthine Muthaura et al., 2015
Croton macrostachyus Del. Fruit MeOH 0.94a(FAC-2/Eth) [3H]-Hypoxanthine Sorsa et al., 1992
Jatropha curcas L. Leaf EA 2.39a(K1) 5.06a(NF54) [3H]-Hypoxanthine Abiodun et al., 2011
MeOH 11.53a(K1) 31.09a(NF54) [3H]-Hypoxanthine Abiodun et al., 2011

Lamiaceae Ajuga remota Benth. Whole plant MeOH 45.9a(D6), 77.8a(W2) [3H]-Hypoxanthine Muthaura et al., 2015
a a
Ocimum gratissimum L. Leaf EA 1.8 (K1), 3.6 (NF54) [3H]-Hypoxanthine Abiodun et al., 2011
MeOH 22.52a(K1) 29.61a(NF54) [3H]-Hypoxanthine Abiodun et al., 2011
Amaryllidaceae Allium sativum L. Rhizome H2O 48.0a(3D7) Microscopy Manu et al., 2013
Lythraceae Lawsonia inermis L. Leaf PET 27.0b(FcB1-Columbia) [3H]-Hypoxanthine El Babili et al., 2013
Meliaceae Azadirachta indica A. Juss. Leaf EtOH 2.4a(D6) [3H]-Hypoxanthine Benoit et al., 1996
Melia azedarach L. Stem bark MeOH 100a(W2) [3H]-Hypoxanthine Muthaura et al., 2015
Meliaceae Ekebergia capensis Sparrm Stem bark MeOH 10.5a(D6) [3H]-Hypoxanthine Muthaura et al., 2015
Melianthaceae Bersama abyssinica Fresen. Leaf EtOH 4a(FAC-2/Eth) [3H]-Hypoxanthine Kassa et al., 1998

Table 3 (continued)

22
Family Species Parts use Solvent Anti-malarial activity IC50 in Method References
µg/ml(a) or µM(b) or nM(c) or
ng/ml(d) and strain

Menispermaceae Cissampelos mucronata A. Rich Root EtOH 1.3a(KI) [3H]-Hypoxanthine Gessler et al., 1994
EA 0.38a(KI) [3H]-Hypoxanthine Gessler et al., 1994
H2O 1.2 a(KI) [3H]-Hypoxanthine Gessler et al., 1994
Cissampelos pareira L. Root bark MeOH 5.2a(D6), 6.5a(W2) [3H]-Hypoxanthine Muthaura et al., 2015

H2O 6.8a(D6), 9.3a(W2) [3H]-Hypoxanthine Muthaura et al., 2015


a
Moringaceae Moringa oleifera Lam. Leaf EtOH 15.18 (3D7) Donkor et al., 2015
Moraceae Ficus sur Forssk. Leaf MeOH 7.9a(D6) [3H]-Hypoxanthine Muthaura et al., 2015
Stem bark MeOH 8.5a(D6), 15.9a(W2) [3H]-Hypoxanthine Muthaura et al., 2015

Root bark MeOH 16.5a(D6), 17.3a(W2) [3H]-Hypoxanthine Muthaura et al., 2015


a a
Myrtaceae Eucalyptus globulus Labill. Leaf DCM:MeOH 16.8 (3D7) 26.45 DD2) pLDH Zofou et al., 2011
Olacaceae Ximenia americana L. Stem bark H2O >100a(D6) >100a(W2) [3H]-Hypoxanthine Muthaura et al., 2015
Oleaceae Olea europaea L. Leaf MeOH:H2O 15a(D10) pLDH Clarkison et al., 2004
Rubiaceae Gardenia ternifolia Schumach. & Whole part Acetone 0.94a (D6), 1.06a(W2) [3H]-Hypoxanthine Ochieng et al., 2010
Thonn.
Rutaceae Citrus limon L. Osbeck Leaf DCM 5a(D10), 5.99a(DD2) pLDH Melariri et al., 2012
Sapindaceae Dodonaea angustifolia L.f. Leaf MeOH 32.1a(W2) [3H]-Hypoxanthine Muthaura et al., 2015
H2O >100a (W2) [3H]-Hypoxanthine Muthaura et al., 2015
Dodonaea viscosa (L.) Jacq. Leaf MeOH:H2O 15.5a(D10) pLDH Clarkison et al., 2004
Buddlejaceae Buddleja polystachya Fresen. Whole plant MeOH 1.35a Microscopy Barzinji et al., 2014
Solanaceae Lycium shawii Roem. & Schult. Aerial part H2O 1.36a Microscopy Barzinji et al., 2014
MeOH 7.75a(KI) pLDH Abdel-Sattar et al., 2009
Withania somnifera L. Root bark MeOH >100 a(D6 & W2) [3H]-Hypoxanthine Muthaura et al., 2015
H2O >100a(D6 & W2) [3H]-Hypoxanthine Muthaura et al., 2015
Vitaceae Cissus rotundifolia Vahl Leaf MeOH 58a Microscopy Alshawsh et al., 2009
H2O 34.7a Microscopy Alshawsh et al., 2009
Zygophyllaceae Balanites aegyptiaca (L.) Del. Root bark MeOH 8.9a(W2) [3H]-Hypoxanthine Muthaura et al., 2015
Seed H2O 68.26a (NF54) Microscopy Kusch et al., 2011
Zingiberaceae Zingiber officinale Roscoe Rhizome MeOH 38a (D6) Not mentioned Lawal et al., 2015

n = number of consulted studies


Solvents: DCM, Dichloromethane; EtOH, EA, Ethyl acetate; EtOH, ethanol; IOH, Isoamyl alcohol; MeOH, methanol; H2O, water; PET, petroleum ether.

23
Table 4. In-vivo anti-plasmodial activities of medicinal plants used for the treatement of malaria
and related symptoms in Ethiopia

Family Plant species Part Solvent % of inhibition/Dos# Reference


Acanthaceae Adhatoda schimperiana Leaf EtOH 84.7% / 600mg/kg/d Peteros and Melaku, 2012
(Hochst.)
Asphodelaceae Aloe sp. Leaf EtOH 73.09% / 650mg/kg/d Mesfin et al., 2012
Leaf Water 58.1% / 650mg/kg/d Mesfin et al., 2012
Apocynaceae Acokanthera schimperi (A. DC.) Leaf MeOH 34.8% / 600mg/kg/d Mohammed et al., 2014
Schweinf.
Asparagaceae Asparagus africanus Lam. Root EtOH 46.1% / 600mg/kg/d Dikasso et al., 2006a
Aerialpart EtOH 40% / 600mg/kg/d Dikasso et al., 2006a
Asteraceae Artemisia afra Jacq Leaf EtOH 77.45%/100mg/kg/d Gathirwa et al., 2007
Leaf Water 70.25%/100mg/kg/d Gathirwa et al., 2007
Artemisia annua L.* Aerial part Dichlorom 83.28%, 200mg/kg Ramazan et al., 2010
ethane
Brassicaceae Brassica nigra (L.) K.Koch Seed MeOH 53.13% / 400mg/kg/d Muluye et al., 2015
Croton macrostachyus Del. Leaf Water 50%/600mg/kg/d Mohammed et al., 2014
Compositae Echinops kebericho Mesfin Root EtOH 57.29%, 500mg/kg/d Toma et al., 2015
Fabaceae Calpurnia aurea (Ait.) Benth Leaf MeOH 36.6% / 60mg/kg/d Eyasu et al., 2013
Tamarindus indica L. Fruit Water 81.09% / 600mg/kg/d Mesfin et al., 2012
Clerodendrum myricoides Leaf MeOH 82.5% / 600 mg/kg/d Deressa et al., 2010
(Hochst.) R.Br. ex Vatke
Ocimum gratissimum L. Leaf Water 88% / 2000 mg/kg/d Murithi et al., 2014
Ocimum lamiifolium Hochst. ex Leaf Water 35.53 % / 600 Kefe et al., 2016
Benth mg/kg/d.
Lamiaceae Ajuga remota Leaf MeOH 66.7%/ 100mg/kg/day Nardos and Makonnen,
2017
Meliaceae Azadirachta indica A. Juss. Root Water 48%/200mg/kg/day Priyanka et al., 2013
Melia azedarach L. Root EtOH 31.45% / 800mg/kg/d Priyanka et al., 2013
Menispermacea Cissampelos mucronata A. Rich Stem bark EtOH 47.5%/400mg/kg/d Assefa et al., 2007
e Cissampelos pareira L. Stem bark MeOH Significant inhibition Singh and Banyal, 2011
Moraceae Ficus platyphylla Del. Root bark MeOH ** Shittu et al., 2011
Myrtaceae Syzygium guineense (Willd.) Leaf MeOH 45.05% / 400mg/kg Zeleke, 2015
DC.
Olacaceae Ximenia americana L. Seed EtOH 36.49%/100mg/kg Gathirwa et al., 2007
Phytolaccaceae Phytolacca dodecandra L'Hér. Fruit EtOH 55.24% /400mg/kg Adinew, 2014
Ranunculaceae Nigella sativa L. Leaf CHCl3 70.59%/100mg/kg Abdulelah et al., 2007
Rhamnaceae Ziziphus mauritiana Lam Root n-butanol 63.6%/400mg/kg Mishra and Bhatia, 2014
Santalaceae Osyris quadripartita Salzm. ex Root EtOH 41.3% / 600mg/kg Girma et al., 2015
Decne
Sapindaceae Dodonaea angustifolia L.f. Seed MeOH 67.51% / 600 mg/kg. Amelo et al., 2014
Sapindaceae Dodonaea angustifolia L.f. Leaf MeOH 84.52% / 600mg/kg Deressa et al., 2010
Simaroubaceae Brucea antidysentrica J.F. Mill. Root bark CHCl3 47.7%/ 600mg/kg Kefe et al., 2016
Solanaceae Withania somnifera L. Root *** 50.43% /600 mg/kg Dikasso et al., 2006b
Root bark *** 29.13% / 600 mg/kg Dikasso et al., 2006b
*used as a reference for comparison
**at 300 mg/kg showed markedly reduced parasitaemia about 43.50% and a mean survival time of 28 days postinfection
***the solvent used was not mentioned
#
All the study used a mice model- infected with quloroquinine sensitive P. berghei (ANKA strain)

3.5 Anti-plasmodial Compounds Isolated from the Plants

24
The active anti-plasmodial metabolites from some of the plant species used in the

traditional treatment of malaria and related symptoms in Ethiopia have been isolated. Among

the identified compounds, the majorities were alkaloids and terpenoids chemical classes (Table

5 and Figure 3).

Table 5. Anti-plasmodial activity of isolated compounds from plants documented in this study.

Anti-malarial activity IC50


in µg/ml(a) or µM(b) or
Constituents Chemical class Plant species Reference
nM(c) or ng/ml(d) and
strain
Ergosterol-5,8- 8.2a
Steroid Ajuga remota Benth Ntie-kang et al., 2014
endoperoxide(1) (FCA 20/GHA)
Allicin(2) Allium sativum L. * Coppi et al., 2006
Ajoene(3) Allium sativum L. ** Perez et al., 1994
5.5a (pow)
Acacetin(4) Flavanoids Artemisia afra Jacq Pillay et al., 2008
8.1(Dd2)
Oketch-Rabah and
Nyasol(5) Lignanes Asparagus africanus Lam. 12a(Dd2)
Dossaji, 1997
Oketch-Rabah and
Muzanzagenin(6) Sapogenin Asparagus africanus Lam. 16a(Dd2)
Dossaji, 1997
Meldenin(7) Triterpenoids Azadirachta indica A. Juss 5.23a(K1) Joshi et al., 1998
0.72a(K1)
Gedunin(8) Triterpenoids Ekebergia capensis Sparrm
Bray et al., 1990
Punicalagin(9) Tannins Combretum molle R.Br 27.73a(3D7) Asres et al., 2001
(1S-11R-13S-14S-24R-26S)-
13,26-Dimethyl-2,15-dioxa-
12,25-dia- zatricyclo Piperidinealkaloids Carica papaya L. 0.2b(K1) Julianti et al., 2014
[22.2.2.211,14]triacontane-
3,16-dione((þ)-carpaine(10)
6-(8-Methoxy-8-oxooctyl)-2-
methylpiperidin-3-yl8-(5-
Piperidinealkaloids Carica papaya L. 1.8b(K1) Julianti et al., 2014
hydroxy-6-methylpiperidin
-2-yl)octanoate (11)
13,26-Dimethyl-2,15-dioxa-
12,25-
Piperidinealkaloids Carica papaya L. 1.0 b(K1) Julianti et al., 2014
diazatricyclo[22.2.2.211,14]
triacontane-3,16-dione(12)
Bisbenzylisoquinoli Cissampelos mucronata A.
Curine(13) 101c Tshibangu et al., 2003
ne alkaloids Rich
Cissampelos mucronata A.
R,S-tubocurine(14) 168 c Tshibangu et al., 2003
Rich
Cissampelos mucronata A.
Compound (15) 101 c Tshibangu et al., 2003
Rich
7-deacetoxy-7-oxogedunin b
Limonoids Ekebergia capensis Sparrm 6 (FCR-3) Onguéné et al., 2013
(16)
2,3,22,23-Tetrahydroxy-
2,6,10,15,19,23-hexamethyl- Triterpenoid 18b(FCR-3)
Ekebergia capensis Sparrm Murata et al., 2008
6,10,14,18- derivative 7(K1)
tetracosatetraene(17)
Naphthalene
2-methylnapthazarin (18) Euclea divinorum Hiern 0.5(W2) Ng'ang'a, 2013
derivatives
Otostegindiol(19) Labdane diterpenoid Otostegia integrifolia Benth *** Endale et al., 2013
178.12d(D6)
Plumbagin(20) Napthoquinone Plumbago zeylanica L. Dharani et al., 2008
188.8d(W2)
Sesquiterpene Chukwujekwu et al.,
Vernolide(21) Vernonia amygdalina Del. 1.87a(D10)
lactones 2009
Sesquiterpene Chukwujekwu et al.,
Vernodalin(22) Vernonia amygdalina Del. 0.52 a(D10)
lactones 2009
Cyclopeptide
Mauritine M(23) Ziziphus mauritiana Lam. 3.7b(K1) Panseeta et al., 2011
alkaloids

25
Cyclopeptide
Nummularine H (24) Ziziphus mauritiana Lam. 4.2b(K1) Panseeta et al., 2011
alkaloids
Cyclopeptide
Hemsine A (25) Ziziphus mauritiana Lam. 7.3b(K1) Panseeta et al., 2011
alkaloids
*The 50 µM dose of allicin, the allicin-treated mice had a 94% decrease in parasitemia compared to controls.
**29% inhibition at the dose of 12.5mg/kg.
*** 73.16% of inhibition in a dose of 100mg/kg/d.
O-

S S
S+ S
S 3
O
O 2
OH

1
OCH3 O CH3
H
O
H OH
HO O
H
O
H CH3

H
OH

OH O 4
O 6
OH 5
O OH

O
OH
CHOH NH

OH O
O
O
O O
O OH
O
O
O
OH
O OCOMe
O O
H
OAc OH NH
O OH O
7 8 OH CO O
O H

OC
H O 10
OH CO
H OH

OH OH OH

OH
OH OH OH 9
OCH3
O

N 1
NH O NH
OH
H3C H CH3
H O
O O N
OH 1'
O O
O O
O

NH OH
NH

OCH3
12 13=H1’=
11
14= H1’=
OCH3 OH
O

OH
N
O
H3C H H
H OH
OH
N
O 17
O

OH O
O OH O O

O
OCH3 O
HO
15 16 O
O
H

H
HO O OCH3 O
O
Me OH O
O O
H
O 21
O
20
N HN
N OH OCH3
HO O
18 HN H
19
C6H5H2C O
O O
O
H
NH O
O
OH
O N HN
N
O
C6H5H2C NH(CH3) HN

24 O
O

O
H NH O
O N
H
O
26
O
22
H
H
O
HN
N H
H
HN
O
O

N N(CH2)2
H
25
Figure 3. The chemical structures of anti-malarial compounds isolated from the plant species.

DISCUSSION

Malaria, is a devastating disease in Sub-Saharan Africa, including Ethiopia (Murray et al.,

2012). The current malaria control measures targeting the mosquito vector with insecticides

have helped to alleviate the malaria burden in many endemic areas (Greenwood et al., 2008).

However, due to the overwhelming nature of the disease, wide ranges of differences in the

coverage of services and distribution of health facilities that persists among regions as well as

between urban and rural areas, and the failure of most affordable drugs to treat malaria due to

resistance by the parasite, there is still an urgent need to search for new and more effective

antimalarial drugs.

Traditional medicines have been used to treat malaria for thousands of years and are the

source of the two main groups (artemisinin and quinine derivatives) of modern anti-malarial

drugs (Willcox and Bodeker, 2004). In Ethiopia, different sociocultural groups possess detailed

knowledge on the use of antimalarial plants that has been transferred from one generation to

another usually through the word of mouth without proper documentation (Asnake et al., 2016).

It is also believed that this knowledge, belonging to traditional healers is becoming transmitted

less and tends to disappear (Desissa and Binggeli, 2000). Additionally, there is a danger of

losing the knowledge due to the rapid degradation of natural habitats and ecosystems and thus

there is a need for its documentation (Asnake et al., 2016).

In this study, the traditional healers reported that they conventionally define malaria and

related illnesses in terms of fever, chilling, and/or headache. The sociodemographic

characteristics of the respondents revealed men have more involvement in traditional medical

27
practice than women, which could be due to the fact that parents usually prefer boys in the

transfer of the indigenous knowledge. Similar results were observed from other studies in

Ethiopia (Giday et al., 2009; Yirga and Zeraburk, 2011; Suleman and Alemu, 2012). Most of

the traditional medical practitioners (83%) were ≥ 40 years old, indicating indigenous

knowledge of traditional herbal medicine is predominantly handled by older people and there is

a less tendency of transfer to the new generation. This could be attributed to the ever-increasing

influence of modernization, leading to loss of interest among the younger generation to learn

and practice it (Giday et al., 2009). Consequently, there is an urgent need for the documentation

of this knowledge. Most of the healers (63.7%) reported that they acquired the knowledge from

their family; while the remaining proportion gained the knowledge through other means such as

from friends, local elders, Quran and neighbour. Similar findings have also been reported in

other studies, where the most frequently cited sources of the indigenous knowledge were family

members (Gedif and Hahn, 2002; Weldegerima et al., 2007).

In this study a wide variety of medicinal plant species (n = 28) belonging to 24 families

were reported by the traditional healers as being used for the treatment of malaria and related

symptoms in Jimma zone. The majority of the medicinal plants used were trees, followed by

shrubs, which is in fact in agreement with studies conducted in Ethiopia (Suleman et al., 2009),

Kenya (Muthaura et al., 2007a, b) and Namibia (Cheikhyoussef et al., 2011), where most of the

anti-malarial herbal remedies were obtained from trees and shrubs. The current study has also

revealed that the leaves part of the medicinal plants was most frequently used for the treatment

of malaria and related symptoms in the study area. Oral based herbal medicines were

commonly prepared using water and honey as excipients. This is in line with studies conducted

elsewhere in Ethiopia where water, honey and milk were the predominant vehicle in the

preparation of traditional herbal remedies (Gedif and Hahn, 2002; Seifu et al., 2006; Guji et al.,

2011).

28
The study results revealed that Allium sativum L. and Carica papaya L. showed the

highest incidence of use, claimed by traditional healers. A number of studies elsewhere in

Ethiopia have also revealed that these species are most commonly used by traditional healers

and communities in the treatment of malaria and related symptoms (Abera, 2003; Berhanu et

al., 2006; Etana, 2010; Parvez and Yadav, 2010; Karunamoorthi et al., 2013; Getaneh and

Girma, 2014). Furthermore, Vernonia amygdalina Del., Allium sativum L. and Carica papaya

L. were used to manage malaria and related symptoms in different parts of African countries

(Karunamoorthi et al., 2013; Toyang and Verpoorte, 2013). The fact that the same plants are

used by different communities for a similar indication could possibly show their effectiveness

and need to be subjected to further scientific investigations. The aforementioned species have a

great role in the traditional treatment of different illnesses in addition to malaria and related

symptoms in Ethiopia. For instance, Vernonia amygdalina Del. for tapeworm, ascaris and

stomach ache (Teklehaymanot et al., 2007), Allium sativum L. for wound/sore, cough,

toothache and itching/ scabies (Teklay et al., 2013), Lepidium sativum L. for intestinal

parasites, 'Mich', and headache, and Carica papaya L. for amoebiasis and intestinal parasites

(Mesfin et al., 2009).

The systematic review of this study showed that a large numbers of medicinal plant

species (n=124) were reported to be used in the treatment of malaria and related symptoms in

Ethiopia. Among the plant species commonly claimed to be used in the treatment of malaria

and related symptoms, the most frequently cited by the studies were Allium sativum L., Carica

papaya L., Vernonia amygdalina Del., Lepidium sativum L., and Croton macrostachyus Del.

and Adhatoda schimperiana Hochst. Species of plants that were most frequently cited may be

more effective and need to be subjected to further scientific investigations. There are some

species of plants which were commonly cited in this review and that are also known to be used

as sources of anti-malarial remedies in other parts of the world. For instance, Azadirachta

29
indica A. Juss. is used in Nigeria (Olorunnisola et al., 2013), India, Malaysia and Burkina Faso

(Karunamoorthi et al., 2013). The use of Vernonia amygdalina Del. in the treatment of malaria

was reported from Cameroon (Teklehaymanot and Giday, 2010), Nigeria (Olorunnisola et al.,

2013) and Uganda (Karunamoorthi et al., 2013). Furthermore, Carica papaya L. was used in

Cameroon (Titanji et al., 2008), D.R. Congo (Kalonda et al., 2014), Uganda (Katuura et al.,

2007), and Togo (Karunamoorthi et al., 2013) for the same purpose. The literature review has

also revealed that Leucas stachydiformis Hochst. ex Benth. and Aloe pirottae A. Berger are the

two species of plants endemic to Ethiopia claimed to be used in the treatment of malaria (Etana,

2010; Belayneh and Bussa, 2014). However, there are many more species of plants that are

endemic to Ethiopia within the same genera to be claimed for anti-malarial activity. For

instance, more than 12 endemic Vernonia species were claimed to be having anti-malarial

activity exist in the country. This could be because plants of the same genus produce related

compounds. They could lead to a large natural diversity of derivatives of compound of interest

(Mambu and Grellier, 2008).

This literature search from different studies revealed that a variety of methods are

employed to prepare remedies, including crushing, boiling and squeezing. Certain additives, it

could be water, honey, sugar, milk, local alcohol and butter, are frequently used to improve the

acceptability of some remedies that are taken orally. A combination of two or more herbal

medicines was also reported in some studies, for example Allium sativum L. with Capsicum

annuum L. (Megersa et al., 2013), Lepidium sativum L. with Allium sativum L. (Mesfin et al.,

2009), and Cordia africana Lam. with Zingiber officinale Roscoe (Mesfin et al., 2014).

Combining some plants could have a synergistic or antagonistic effect.

The comparative analysis of the survey with the literature search showed that nearly more

than half of (54%) of medicinal plants documented in the survey has been reported previously

as an anti-malarial plant in literature search. Moreover, a high degree of similarity was

30
observed with the studies conducted in the different areas of Ethiopia. Though the highest

similarity was observed with the study conducted in the nearest area to Jimma (Etana, 2010), a

significant similarity was also demonstrated by the study conducted in area which are far from

Jimma (Regassa, 2013; Abera, 2014). According to Houghton and Manby (1985) this similarity

could reflect environmental factors or study methodologies among communities under study.

Furthermore, 13 plant species that were not reported as anti-malarial plants in literature search

were identified in the ethnomedicinal field survey. This could be due to the fact that Jimma is

in the rich natural flora of the southwest of the country. Moreover, this could depict the

importance of focused ethnomedicinal surveys of plants about enriching information related to

medicinal plants; in addition to the literature search.

The antimalarial activity reports from literature shows that the in-vitro anti-malarial

activity ranges from 0.38 to 100 μg/ml. Among the plants which the in-vitro activities were

reported, Piperidinealkaloids (6-(8-Methoxy-8-oxooctyl)-2-methylpiperidin-3-yl8-(5-hydroxy-

6-methyl piperidin-2-yl)octanoate and 13,26-Dimethyl-2,15-dioxa-12,25-diazatricyclo

[22.2.2.211,14] tri acontane-3,16-dione) (11 and 12, Table 5) of them have shown pronounced

(IC50 ≤ 5μg/ml) and promising (5 μg/ml < IC50 ≤ 15 μg/ml) anti-malarial activities respectively.

For instance, methanolic extract of the fruit of Croton macrostachyus Del., ethyl acetate extract

of the root of Cissampelos mucronata A. Rich. and acetone extract of the whole part of

Gardenia ternifolia Schumach. & Thonn. demonstrated strong anti-malarial activity with IC50

of less than 1 μg/ml which could provide the evidence to support their traditional claim (Sorsa

et al., 1992; Gessler et al., 1994; Ochieng et al., 2010). Furthermore, the dichloromethane

extract of leave part Artemisia afra Jacq. ex Willd., petroleum ether and isoamyl alcohol

extracts of leave of Vernonia amygdalina Del., ethylacetate extract of Ocimum gratissimum L.,

ethanol extract of Azadirachta indica A. Juss. and Bersama abyssinica Fresen. leaves, aqueous

and ethanolic extract of leave and root of Cissampelos mucronata A. Rich and leaves of

31
Buddleja polystachya Fresen have been reported to have promising anti-plasmodial activity

(IC50 ≤ 5 μg/ml) (Gessler et al., 1994; Benoit et al., 1996; Kassa et al., 1998; Tona et al., 2004;

Abiodun et al., 2011; Barzinji et al., 2014).

In-vivo antiplasmodial activity evaluation of crude extracts and fractions from Ethiopian

medicinal plants showed good activity against Plasmodium berghei, ANKA (Table 4). The

high activities demonstrated by these plants render them good candidates for the identification

and isolation of anti-malarial compounds that could serve as a backbone for new drug

development.

The literature search also found that active anti-plasmodial metabolites were also isolated

from some of the plant species used in the traditional treatment of malaria and related

symptoms in Ethiopia. Alkaloids and terpenoids were the major chemical classes identified. For

instances, Julianti et al. (2014) isolated the piperidine alkaloids such as compound 10, 11 and

12 (Table 5, Figure 3) from the leave of Carica papaya L., which demonstrated the anti-

malarial activity with IC50 of 0.2 µM, 1.8 µM and 1.0 µM against P. falciparum (K1 strain),

respectively. Another study conducted by Angerhofer et al. (1999) found that among 16

compounds, curine (13) and compound (15) (Figure 3) (IC50 values around 101 nM) and R,S-

tubocurine (14) (IC50 values around 168 nM) (Table 5), are the most promising

bisbenzylisoquinoline alkaloids majorly isolated from the root of Cissampelos mucronata A.

Rich.. Panseeta et al. (2011) also isolated anti-plasmodial cyclopeptide alkaloids, Mauritine

M(23), Nummularine H(24) and Hemsine A(25) from the root of Ziziphus mauritiana Lam..

The isolated alkaloids exhibited potent anti-plasmodial activity against the parasite P.

falciparum with the IC50 ranging from 3.7 to 10.3 µM. The bioactive triterpenoids, Meldenin

(7), Gedunin (8), and 2,3,22,23-Tetrahydroxy-2,6,10,15,19,23-hexamethyl-6,10,14,18-

tetracosatetraene (17) were obtained from Azadirachta indica A. Juss. and Ekebergia capensis

Sparrm. Gedunin (8) is the most active against P. falciparum (K1 strain) with IC50 of 0.72

32
µg/ml (Bray et al., 1990; Joshi et al., 1998; Murata et al., 2008). Moreover, many active

metabolites have been also isolated and characterized from Vernonia amygdalina Del. leaves,

such as sesquiterpene lactones, steroidal saponins (vernoniosides), and flavonoids (luteolin and

its glycosides). The class of sesquiterpene lactones is probably the most peculiar of this plant

and it includes the highly oxygenated derivatives vernolide (21), vernodalol, vernodalinol,

epivernodalol, vernodalin (22), vernomygdalin and vernolepin. Vernolide (21) and vernodalin

(22) (Table 5, Figure 3) exhibited IC50 of 1.87 and 0.52 μg/mL, respectively; against P.

falciparum blood stages in-vitro (Abay et al., 2015). Furthermore, Endale et al. (2013) isolated

labdane diterpenoid, Otostegindiol (19) from Otostegia integrifolia Benth. and it was found to

have anti-malarial activity against P. berghie in-vivo with 73.16% of suppression in a dose of

100 mg/kg/d.

In general, traditionally used medicinal plants to treat malaria possess a range of

prospective pharmacologically active compounds. However, the application of plants used in

the therapy of malaria and its associated symptoms have clear limitations. Firstly, there are few

clinical data on safety and efficacy. Secondly, there is no consensus, even among traditional

healers, on which plants, preparations, and dosages are the most effective. Thirdly, the

concentration of active ingredients in a plant species varies considerably, depending on several

factors. Hence, a successful way to conserve and use these antimalarial plants knowledge to

integrate traditional medicine into modern science, is necessary.

CONCLUSION

The result of the current study showed that traditional knowledge is still playing an

important role in the management of malaria and related symptoms in Ethiopia. Allium sativum

L., Carica papaya L., Vernonia amygdalina Del., and Lepidium sativum L. are the most

commonly reported species as anti-malarial plants. Furthermore, the anti-plasmodial activity

33
literature search showed that a traditional claim of some species was supported by bioactivity

reports. Moreover, some species of plants have shown to contain the compounds with known

anti-plasmodial activity. Finally, the finding from this study is potentially useful in the rational

prioritization of plant species for further investigation to determine their efficacy and safety,

which could contribute to the development of new and efficacious malaria treatment options.

ACKNOWLEDGMENTS

This study was supported by VLIR-IUC-JU. The authors express their gratitude to local

administrators and traditional healers of Jimma zone for their valuable assistance during data

collection. The authors also acknowledge Mr. Zewude Achiso, Department of Biology, Jimma

University for his assistance in plant species identification.

Authors’ contributions

SS and BDS conceived the idea and designed the study. DK, SB, SM, FG and YM conducted

field survey. TBT, SB and DK performed the literature search. EW and LD analyzed the data.

SS, TBT and DK drafted the manuscript. SS, TBT, MD, EW, LD and BDS critically reviewed

the manuscript. All authors have read and approved the final version.

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Activity and Cytotoxicity of Extracts of Selected Medicinal Plants Used by Traditional Healers
of Western Cameroon. Malar. Res. Treat. doi:10.4061/2011/561342.
Appendex

Appendex 1. Main characteristics of studies (n = 52) included in this literature search

46
Study # of medicinal
Author, Year Place of study Year of Sample Type of
S.No plant reported
study size respondents
for malaria
1 Megersa et al., 2013 West Wollega (Wayu), West 2010 63 TH 4
Ethiopia
2 Abera, 2014 Gimbi, Southwest Ethiopia 2010 195 GI, KI & TH 6
3 Teklay et al., 2013 Kilte, Tigray, Northern Ethiopia 2011 72 TH & KI 5

4 Teklehaymanot and Zegie, Peninsula, Northwestern 2006 200 GI & TH 1


Giday, 2007 Ethiopia
5 Mesfin et al., 2009 WonagoWoreda, Southern 2006 30 TH 6
Ethiopia
6 Kidane et al., 2014 Maale and Ari ethnic, Southern 2012 92 KI 4
Ethiopia
7 Belayneh and Dengego, Eastern Ethiopia 2013 50 GI &TH 4
Bussa, 2014
8 Giday et al., 2010 Sheko ethnic group Bench-Maji 2004 100 KI 2
Zone, Southwest Ethiopia
9 Belayneh et al., Babile Wereda, Eastern Ethiopia 2009 54 GI & KI 7
2012
10 Tolossa et al., 2013 South Omo, Southern NA 50 TH 3
11 Flatie et al., 2009 Benishangul-Gumuz west NA 1240 GI & TH 3
Ethiopia
12 Gedif and Hahn, Butajira & Addis ababa, Central NA 44 TH 8
2002 Ethiopia
13 Yineger et al., 2008 Oromo ethnic group, Southwest 2006 45 TH 1
Ethiopia
14 Lulekal et al., 2008 Manaangatu (Bale), Southeastern 2004 70 TH 1
Ethiopia
15 Abbink, 2002 Suri (Surma), people of Southern 1999 NA NA 1
Ethiopia
16 Abera, 2003 Jimma zone, Southwest Ethiopia 2000 NA TH 2
17 Bekalo et al., 2009 Konta, Southern Ethiopia 2007 70 KI 4
18 Bekele and Reddy, Guji, Borena, Oromia, Ethiopia 2013 48 TH 4
2015
19 Dori et al., 2012 Konso, South Ethiopia 2009 209 GI 10
20 Gashe and Worku, Eastern Wollega, Western 2006 344 GI 1
2007 Ethiopia
21 Gabriel and Guji, Agaro district, Jimma Zone, 2013 440 GI 3
2014 Southwest Ethiopia
22 Giday et al., 2009b Bench, South Ethiopia 2006 10 KI 1
23 Giday et al., 2010 Sheko ethnic group, Southwest 2004 100 KI 2
Ethiopia
24 Guji et al., 2011 Metekel Zone, Benishangul- NA 600 GI 5
Gumuz Mid-West Ethiopia
25 Hunde et al., 2006 East Shewa Zone, Central eastern 2001 80 GI & KI 4
Ethiopia
26 Abbink, 1993 Kafa, Southwestern Ethiopia 1991 NA NA 3
27 Lulekal et al., 2013 Ankober District, North Shewa 2011 352 TH 1
Zone, Amhara Region, Ethiopia
28 Mesfin et al., 2014 Amero district, Southern Ethiopia 2012 17 TH 13

29 Ragunathan and Bahr Dar, Northwest Ethiopia 2005 NA NA 1


Abay, 2009

47
30 Regassa, 2013 Hawassa, Southern Ethiopia 2012 140 TH & KI 11
31 Seid and Tsegay, Tehuledere district, South Wollo, 2009 67 GI & KI 5
2011 North Ethiopia
32 Suleman et al., 2009 Assendabo (South-West) Ethiopia 2007 NA GI 13

33 Suleman and Nekemte Town, East Wollega 2006 376 GI 4


Alemu, 2012 (Oromia), Ethiopia
34 Tadesse et al., 2005 Seka Chekorsa, Jimma zone, 2003 62 KI 3
Ethiopia
35 Zerabruk and Yirga, Gindeberet District, Western 2010 120 GI 2
2012 Ethiopia
36 Yirga, 2010b Endrta District, South-eastern 2009 35 KI 1
Tigray, Northern Ethiopia
37 Yirga, 2010a Central Zone of Tigray, Northern 2008 12 TH 1
Ethiopia
38 Zenebe et al., 2012 Asgede Tsimbila District, North 2010 20 KI 1
westernTigray,
39 Seifu et al., 2006 Chifra district, Afar region, North 2003 29 TH 6
eastern Ethiopia
40 Wondimu et al., Dheeraa town, Arsi Zone, 2002 75 GI 1
2007 Ethiopia
41 Giday et al., 2007 Benishangule and Amhara, North 2004 NA GI 16
Ethiopia
42 Teklehaymanot and Debub Omo Zone, Ethiopia 2006 206 GI 7
Giday, 2010
43 Teklehaymanot et Debrelibanos, Northern central 2006 250 GI 3
al., 2007 Ethiopia
44 Getaneh et al., 2014 Debrelibanos, Northern central 2009 60 KI 1
Ethiopia
45 Gebeyehu, 2011 West Gojam, Northwest Ethiopia 2013 80 GI & KI 8

46 Mesfin et al., 2012 Shinile District, Somali Region, 2007 15 TH 27


Ethiopia
47 Yirga, 2010 Endrta District, South-eastern 2009 35 KI 1
Tigray, Northern Ethiopia
48 Etana, 2010 Goma Wereda, Jima Zone, 2010 100 GI & KI 8
Southwest Ethiopia
49 Amenu, 2007 West Shoa, Central eth 2006 72 GI & KI 6
50 Beyene, 2011 Wondo Genet Sidama zone, 2011 80 GI & KI 7
south, Ethiopia
51 Gebrehiwot, 2010 Seru Wereda, Arsi zone of 2010 80 GI 6
Oromia region, Ethiopia
52 Chekole et al., 2015 Tara-gedam and Amba remnant 2010 105 GI & TH 5
forests
KI = Key Informant, GI = General Informant, TH = Traditional healer, NA= not available

48
High contribution to
global death § Poor access and affordability Anti-malarial drugs
§ Drug resistance

Alternative treatment
Loss of indigenous strategies
knowledge

Ethno-medicinal study

§ Lack of documentation
§ Acculturation
§ Documentation § Deforestation
§ Validation § Urbanization
§ New anti-malarial drug § Drought
§ Lead compound
§ Integration in to health
care system