Parasitology International 66 (2017) 713–720

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Parasitology International
journal homepage: www.elsevier.com/locate/parint

Review

Medicinal plants for in vitro antiplasmodial activities: A systematic review of MARK

literature
Martha Tibebu Lemmaa,1, Ali Mahmoud Ahmedb,1, Mohamed Tamer Elhadyc,1, Huyen Thi Ngod,
Tran Le-Huy Vue, To Kim Sangf, Eduardo Campos-Albertoa, Abdelrahman Sayedb,
Shusaku Mizukamia, Kesara Na-Bangchangg, Nguyen Tien Huya,h,⁎, Kenji Hirayamai,
Juntra Karbwanga,⁎⁎
a
Department of Clinical Product Development, Institute of Tropical Medicine (NEKKEN), Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto,
Nagasaki 852-8523, Japan
b
Faculty of Medicine, Al-Azhar University, Cairo 11884, Egypt
c
Faculty of Medicine, Zagazig University, Sharkia, 44511, Egypt
d
Department of Medicine, University of Medicine and Pharmacy, Ho Chi Minh city, Viet Nam
e
Advanced Research Center Inc., 1020 S Anaheim Blvd, Anaheim, CA, United States
f
Ho Chi Minh City Oncology Hospital, Ho Chi Minh City, Viet Nam
g
Graduate Studies, Chulabhorn International College of Medicine, Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma,
Thammasat University, Pathum Thani 12121, Thailand
h
Evidence Based Medicine Research Group, Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City 70000, Viet Nam
i
Department of Immunogenetics, Institute of Tropical Medicine (NEKKEN), Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki
852-8523, Japan

A R T I C L E I N F O A B S T R A C T

Keywords: The increasing resistance of malaria to drugs raise the need to new antimalarial agents. Antiplasmodial herbs and
Traditional herbs their active compounds are the most promising source the new antimalarial agents. This study aimed to identify
Systematic review the medicinal plants with very good in vitro antiplasmodial activities, with half-maximal inhibitory concentra-
Antiplasmodial tion (IC50) ≤ 1 μg/ml, and to determine trends in the process of screening their antiplasmodial activities. A total
In vitro
of 58 reports published in the English language were retrieved from the bibliographical databases. Screening and
IC50
data extraction were performed by two independent reviewers. The herbs were categorized as very good, good,
moderate and inactive if the IC50 values were < 0.1 μg/ml, 0.1–1 μg/ml, > 1–5 μg/ml and > 5 μg/ml respec-
tively. We documented 752 medicinal plants belonging to 254 genera. The majority of the plants were reported
from Africa followed by Asia. The traditional use for malaria treatment was the most common reason for the
selection of the plants for investigation. About 80% of the plants experimented were reported to be inactive.
Among plants identified as having very good to good antiplasmodial crude extracts are Harungana mada-
gascariensis, Quassia africana, and Brucea javanica, while Picrolemma spruce, Aspidosperma vargasi, Aspidosperma
desmanthum, and Artemisia annua were reported to have individual compound isolates with very good anti-
plasmodial activities. In conclusion, the number of plant species assessed so far is still small compared with the
stock in nature's plant library. A mechanism of systematically approaching and exploring the untouched plant
genera needs to be designed.

1. Introduction has been established through the application of traditional medicines

and natural venoms for thousands of years [1–3]. NPs can end up being
The close association between medicine and natural products (NPs) the final drug entity or the source of novel drug structures for malaria

Abbreviations: IC50, Half-maximal inhibitory concentration; NP, Natural products

⁎
Correspondence to: N. T. Huy, Evidence Based Medicine Research Group, Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City, Viet Nam.
⁎⁎
Correspondence to: J. Karbwang, Department of Clinical Product Development, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki 852-8523, Japan.
E-mail addresses: ali.mahmoud@azhar.edu.eg (A.M. Ahmed), mizukami@nagasaki-u.ac.jp (S. Mizukami), tienhuy@nagasaki-u.ac.jp, nguyentienhuy@tdt.edu.vn (N.T. Huy),
hiraken@nagasaki-u.ac.jp (K. Hirayama), karbwangj@nagasaki-u.ac.jp (J. Karbwang).
1
M.T.L., A.M.A., and M.T.E. contributed equally to this work.

http://dx.doi.org/10.1016/j.parint.2017.09.002
Received 12 May 2017; Received in revised form 25 July 2017; Accepted 6 September 2017
Available online 07 September 2017
1383-5769/ © 2017 Elsevier B.V. All rights reserved.
M.T. Lemma et al.
treatment, which has been a challenge for treatment and control stra-
tegies throughout the world. NPs have historically been a mainstay of
treatment modality in different parts of the world. Research on anti-
plasmodial herbs or their components, like artemisinin, has been one of
the major interesting herbal topics in recent years. Despite being a
much less expensive approach to antimalarial discovery compared to
the synthesis of brand new chemical antiplasmodial drugs [4], it is not
always clear how scientists select their study plants for this purpose.
A convenient approach has been to explore traditionally used
medicinal plants with the claim of effectiveness by herbalists. In this
instance, it is common to study the in vitro activity of individual plants
[5–10] or to ascertain the potential synergistic effects of herbs used in
combination [11–14]. Another approach has been to study plants re-
lated to an already efficacious plant species. Zhu et al. indicated that
drug-like structures are distributed in related groups of species [15]. A
less commonly employed procedure is the reverse pharmacology ap-
proach for traditional medicine which depends on information from the
traditional practice of plants usage [16]. Classically, the development of
the drug passes from laboratory to clinic, but in reverse pharmacology,
it is reversed to pass from clinic to laboratory, hence the name [16].
Due to the emergence of drug resistance to the current anti-
plasmodial agents [17,18], the discovery of new antimalarial drugs is
most urgent. World Health Organization (WHO) in 2013 estimated that
the majority of healthcare needs in developing countries were met
through traditional health care practices [19]. However, considering
the economic cost of synthesizing new drugs, scientists interested in the
development of antimalarials of plant background are in need for in-
formation about the status of previous in vitro antiplasmodial herbs.
This systematic review will help to summarize the exploration trends of
plants for their medicinal antiplasmodial activity, identify anti-
plasmodial herbs with IC50 values ≤1 μg/ml and provide a baseline for
further research to discover effective anti-malaria natural products.
2. Methods
We registered the study in the PROSPERO international prospective
register of systematic reviews (PROSPERO record: CRD42015015882)
and conducted it in accordance with the PRISMA statement [20]. We
retrieved published papers from the online bibliographical databases:
PubMed, Scopus, WHO Global Library, Virtual Health Library and
Google Scholar. Inside the databases, we used key terms for article
search including “Traditional Herbs AND Malaria” or “Traditional
medicine AND Malaria” or “Traditional medicine AND antiplasmodial”.
Non-English articles, reviews, conference articles, thesis, letters and
any other reports that are not original were excluded from this sys-
tematic review. We imported and saved the data to EndNote X7 soft-
ware (Thompson Reuter, CA, USA), deleted the duplicated references
both manually and using the built-in feature of EndNote library, ex-
ported the data to Excel 2010, screened the titles and abstracts,
screened the full texts, and finally extracted relevant data. Two in-
dependent reviewers performed each of these steps. When in dis-
agreement, a discussion has been conducted until we reached a con-
sensus. A flow chart showing these steps can be seen in Fig. 1.
Variables assessed in this review include part of plant tested, type of
solvent used for extraction, type of extract (crude vs a specific isolated
compound), plant family, region/country of origin, and effect on
parasite growth inhibition.
We used the definition of Rasoanaivo et al. who classified the an-
tiplasmodial extracts into very good, good, good to moderate, weak,
very weak, and inactive when their IC50 were < 0.1, 0.1–1, 1.1–10,
10.1–25, 25.1–100, and > 100 μg/ml respectively, as a source to define
our active antiplasmodial herbs [21,22]. As we intended to highlight
the good and very good antiplasmodial herbs, we carried out some
slight modification on the previous classification to make our results
robust and clear. Therefore, we classified the antiplasmodial activities
of the plant extracts against Plasmodium falciparum species based on
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Parasitology International 66 (2017) 713–720
their IC50 values into very good, good, moderate and inactive if the IC50
values were < 0.1, 0.1–1, > 1–5, and > 5 μg/ml respectively.
We summarized all data in tables and figures and checked all herbs
in the final analysis against the ‘Toxic Plant Database (2015).’
3. Results and discussion
From the literature published over the period from 1986 to mid-
2014, we included 58 primary published papers for the review (Fig. 1).
We determined the number of plants in each study and their efficacy
based on IC50 (Supplementary Table S1). We identified a total of 977
plant species as having been studied for their potential antiplasmodial
activities. Due to the selective reporting bias present in the literature,
herbs with no or minimal antiplasmodial activities are rarely reported
and as a result, it was only possible to collect data about 752 plant
species, that fall into 254 genera. The most frequently studied genera
include genus Artemisia (Family Asteraceae), Vernonia (Family Aster-
aceae) and Piper (Family Piperaceae).
The total number of plant species explored so far for antiplasmodial
effect is equivalent to 0.25% of the plant species on earth that are re-
gistered botanically (Botanic Gardens Conservation International,
2015). This number is still small compared with the stock in nature's
plant library, indicating that research efforts need to be escalated in
search for antimalarials of natural product origin as the majority of the
currently available antimalarials are of plant background.
Among the reasons for selection of the studied herbs are traditional
use for malaria treatment (73.6%), survey of literature (10.9%), out of
curiosity (by chemical screening or antimicrobial assay) (5.5%), undi-
sclosed reason (5.5%) and traditional use for fever (4.5%). These results
are concomitant with the predetermined four standardized approaches
needed for selection of an anti-infectious NP which are; random se-
lection either by chemical screening or antimicrobial assays, literature
screening, and traditional or ethnomedical usage [23]. The tendency of
researchers to study specific plants with a claim of potential efficiency
from previous use by herbalists reflects the attempt of researchers to be
logical in the selection of their study products, hence increasing the
likelihood of success. In line with the thought of Zhu et al. [15], some
plant species, belonging to 2% of the plant genera tested in the lab, as
well as related species in the same genus were investigated for the
presence of other potentially useful effects. The culture of sticking to
the above justifications for the selection of candidates of experiment
perhaps needs to be modified to approaches that open the horizon for
exploration untouched plant families.
The majority of the herbs (58.3%) were reported from Africa with
South Africa, Ivory Coast and Kenya being the top three countries for
the origin of these herbs. This is followed by herbs of Asian origin
(23.9%) with Indian, Thailand and Vietnamese herbs ranking the top
three. The remaining were of Latin American (13.3%), North American
(2.8%), and European (1.7%) origin. No plants were reported from
Australia or Antarctica.
Based on the definition of antiplasmodial activity classes, 80% of
the investigated herbs turned out to be inactive. The most promising
herbs having IC50 < 0.1 μg/ml are only 0.8% of the total, while the
herbs that show good antiplasmodial activity (0.1 ≤ IC50 ≤ 1 μg/ml)
are only 2.8% of the total (Table 1). On the other hand, the herbs that
show moderate antiplasmodial activity (1 < IC50 ≤ 5 μg/ml) are
16.4% of the total (Fig. 2). Almost all the plants with ‘very good anti-
plasmodial activity’ were reported from studies between 2005 and
2009, as illustrated in Fig. 3. There is a preponderance that these
findings are from a small number of papers with the half reported by
the same group [24–27].
The majority of the herbs that were screened by the in vitro anti-
plasmodial assays were deemed to be ‘inactive’ by the researchers. This
contrasts with the fact that most of the plants were being used tradi-
tionally for generations. Since some societies have been relying on these
for centuries, perhaps some of the final assessment by some in vitro
M.T. Lemma et al.
studies may be an early rejection of potential candidates. Host factors
may play an important role in this discrepancy through level of ac-
quired immunity, host genetic factors unrelated to immunity, and social
behavior of the host (as concomitant self-medication with other po-
tential antimalarial drugs or herbs) [28]. Moreover, the pharmacoki-
netics of the herb, like the difference in distributional barriers and
binding proteins, may be an important host factor that can explain this
discrepancy [29]. Interestingly, one possible reason for this gross dis-
crepancy may be the tendency of researchers to depend on IC50 values.
It is well known that much of what is learned from the in vitro con-
tinuous cultures of P. falciparum, including IC50 measurements, is re-
lated to the erythrocytic stages of the organism only [30]. This means
that it is technically difficult to assess the herbs with mechanisms not
related to the inhibition of growth of the erythrocytic stage of the
parasite. Thus, since the end result from IC50 value based procedures
will be biased-approving herbs with a specific mechanism of action and
excluding others, it would be wise to consider re-evaluating ‘inactive’
herbs by a more holistic approach such as the reverse pharmacology
technique [16].
In addition, an IC50 value from a given plant species depend on
various factors including the variations between species from different
countries and the conditions of cultivation and harvesting. For example,
the IC50 of the herbal tea extracts from the leaves of Artemisia annua,
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Parasitology International 66 (2017) 713–720
Fig. 1. PRISMA flow diagram represent the selection and
the review processes.
was different when used against chloroquine-sensitive D10 P. falci-
parum than when used against chloroquine-resistant W2 P. falciparum
clones [25]. Furthermore, the IC50 values depend on the way of ex-
traction and the type of in vitro assay. Different methods generally yield
different IC50 values [31–34]. For instance, when changing the solvent,
the same herb will give apparent different in the IC50 or even may be
inactive. Mbatchi et al. studied the effect of different solvents (water,
ethanol, and dichloromethane) on 18 antiplasmodial herbs and re-
vealed that the IC50 is different when using the same plant with dif-
ferent solvent [27]. This appeared distinctly with the bark extract of
Uapaca paludosa, which its IC50 was 8 ± 3, 27 ± 6, and > 100 μg/ml
when the solvent was dichloromethane, ethanol, and water respectively
[27]. Similarly, use of non-polar solvents (like ether and chloroform)
will give different results. Tona et al. approved that with Morinda
morindoides since its IC50 was 1.8 ± 0.2 μg/ml with an ether extract
while was > 50 μg/ml with ethanolic extract [35]. Furthermore, the
cultivation methods of Artemisia annua can dramatically affect the yield
of artemisinin [36–39].
Herbs from different countries may have different concentration of
medicinal compounds due to difference in nutrition, soils, weather, Or
other factors. Also, herbs from same countries but harvested in different
seasons may have different concentration of compounds too. For ex-
ample, Nauclea latifolia harvested in September and January had
 Table 1
M.T. Lemma et al.

List of plants (herbs with crude extracts) with very good to good antiplasmodial activities based on IC50 values.

Name of herb Region/country Harvesting Bioassay model IC50 (μg/ml) ± SD Assessment of IC50
season valuesa

Harungana madagascariensis[26] Nigeria ND Ethanolic extraction from (stem bark) tested against Plasmodium falciparum. 0.052–0.517® Very good - good
activity
Quassia Africana[27] South of Congo ND Dichloromethane extract from (root) tested against FcM29 strain of Plasmodium 0.1 ± 0.07 Very good - good
Brazzaville falciparum. activity
Brucea javanica (L.) Merr[56] South Vietnam November Methylene chloride extract from (root) tested against the chloroquine resistant 0.1 Good activity
FcB1/Colombia strain of Plasmodium falciparum.
Enantia polycarpa[57] Ivory Coast ND Extract from (stem bark) tested against chloroquine and pyrimethamine resistant 0.126 Good activity
K1 strain of Plasmodium falciparum.
Cinchona calisaya[58] French Guiana ND Decoction from (stem bark) tested against the chloroquine resistant W2 strain of 0.21 Good activity
Plasmodium falciparum.
Meconopsis simplicifolia[9] Trongsa/Bhutan ND Chloroform crude extract from (aerial part of the plant) tested against the wild type 0.4 Good activity
chloroquine and antifolate sensitive TM4/8.2 (TM4) strain of Plasmodium
falciparum.
Arcangelisia flava (L.) Merr.[56]. South Vietnam November Methylene chloride extract from (stem bark) tested against the chloroquine 0.4 Good activity
resistant FcB1/Colombia strain of Plasmodium falciparum.
Artemisia roxburghiana[59] North-West ND Chloroform extract from (leaves) tested against the chloroquine and 0.42 Good activity
Himalaya pyrimethamine-resistant K1 strain of Plasmodium falciparum.
Strychnos icaja[60] D.R. Congo ND Methanolic extract from (Root bark) tested in vitro against 3D7 and W2 strains of 0.69 ± 0.25 (vs 3D7) and 0.42 ± 0.22 (vs W2). Good activity
Plasmodium falciparum.
Fibraurea tinctoria Lour[56] South Vietnam November Methylene chloride extract from (stem bark) tested against the chloroquine 0.5 ± 0.1 Good activity

716
resistant FcB1/Colombia strain of Plasmodium falciparum.
Catha edulis[61] South Africa ND Cold dichloromethane extract from (roots and leaves) tested against the 0.63 (roots) and 0.77 (leaves) Good activity
chloroquine-sensitive strain (D10) of Plasmodium falciparum.
Nauclea latifolia[40] Ivory Coast September Infusion from (root) tested against the chloroquine sensitive Nigerian strain and the 24 h: 0.9 (vs Nigerian) and 0.6 (vs FcB1)∞ Good activity
chloroquine-resistant FcB1-Colombia strain of P. falciparum.
Casearia sylvestris var. lingua[62] Brazil ND Hexane extract from (stem bark) tested against the chloroquine-resistant FcB1/ 0.9 ± 0.2© Good activity
Colombia strain of Plasmodium falciparum.
Cupania vernalis[62] Brazil ND Hexane extract from (leaves) tested against the chloroquine-resistant 0.9 ± 0.3© Good activity
FcB1/Colombia strain of Plasmodium falciparum.
Abuta grandifolia (Mart.) Bogot'a/Colombia ND Alkaloid crude extract from (leaves) tested against FcB2 strain of Plasmodium <1 Good activity
Sandwith[5] falciparum.
Piper holtonii C. DC[5] Bogot'a/Colombia ND Ethanolic extract from (aerial part of the plant) tested against FcB2 strain of <1 Good activity
Plasmodium falciparum.
Xylopia aromatica (Lam.) Mart[5] Bogot'a/Colombia ND Ethanolic extract from (aerial part of the plant) tested against FcB2 strain of <1 Good activity
Plasmodium falciparum.
Piper cumanense H.B. & K. Bogot'a/Colombia ND Ethanolic extract from (leaves) tested against FcB2 strain of Plasmodium falciparum. <1 Good activity
(Piperaceae)[5]
Simarouba glauca[63] Guatemala ND Dichloromethane plant extracts from (cortex) tested against NF54 and K1 strain of 0.195 ± 0.04 (vs NF54), 0.184 ± 0.024 (vs K1) Good activity
P. falciparum.
Artemisia annua[25] Italy September Herbal tea extracts from (leaves) tested against chloroquine (CQ)-sensitive D10 and 1.11 ± 0.21© (vs D10) and 0.88 ± 0.35© (vs W2) Good activity
CQ-resistant W2 strains of P. falciparum.

Moderate activity: IC50 > 1–5 μg/ml; and inactive: IC50 > 5 μg/ml. ®; data represented as range, ©; the activity is good to moderate, α; 72 h: 0.7 (vs Nigerian) and 0.6 (vs FcB1), ∞; 72 h: 0.8 (vs Nigerian) and 0.7 ± 0.1 (vs FcB1).
ND; no data, SD; standard deviation.
a
Very good activity: IC50 < 0.1 μg/ml; good activity: IC50 = 0.1–1 μg/ml.
Parasitology International 66 (2017) 713–720
M.T. Lemma et al.
Fig. 2. Classification of herbs according to IC50. This classification is based on our defi-
nition which state that the herb, regarding its antiplasmodium activity, is either very
good, good, moderate, or inactive when the IC50 is < 0.1, 0.1–1, > 1–5, or > 5 μg/ml
respectively.
different levels of activity [40]. Therefore, using IC50 value for the as-
sessment of the antiplasmodial activity of medicinal herbs may not be
the best procedure.
Among plants identified as having very good to good (IC50 ≤ 1 μg/
ml) antiplasmodial crude extracts are Harungana madagascariensis,
Quassia africana and Brucea javanica (Table 1). Similarly, individual
pure compounds isolated from Picrolemma spruce, Aspidosperma vargasi,
Artemisia annua and Aspidosperma desmanthum showed very good anti-
plasmodial activity with IC50 < 0.1 μg/ml (Table 2).
Some of herbs with potential in vitro antiplasmodial activity were
not used in traditional medicine for relieving malarial symptoms (like;
Harungana madagascariensis and Picrolemma spruce). On the other hand,
most of the traditionally used herbs for relieving malarial symptoms
were proved to be inactive as mentioned above. The additional file 2
(Supplementary Table S2) shows the reported traditional use of anti-
plasmodial herbs for management of malaria symptoms.
It was not possible to add additional published in vivo studies or
other forms of pre-clinical information for many of the herbs in the list
we developed in this systematic review, though some studies had been
conducted on some of those herbs. Most of these studies reported dif-
ferent results than in vitro assay. To test the discrepancy between in vivo
Fig. 3. The strength of antiplasmodial activity of herbs certified by year range. The years were categorized by intervals of five years per each to help in distribution of reported
antiplasmodial activity over time.
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Parasitology International 66 (2017) 713–720
and in vitro activity, Sumsakul et al. tested the antimalarial activity of
plumbagin by both models and found that in vitro assay produced
moderate to good antimalarial activity, while in vivo assay produced
weak antimalarial activity [41]. This discrepancy is mainly due to the
lipophilicity and hydrophobicity of the drug that decreased its ab-
sorption and subsequently its bioavailability [42]. Most of studies re-
porting in vivo antiplasmodial activities did not focus on bringing pre-
vious findings to the next level of antimalarial drug development. These
next levels like adverse events, other actions, and synergistic effect with
other compounds. In some cases, the experiments focused on pharma-
cologic effects that are not related to the antiplasmodial effects. For
example, the aqueous stem bark extract of Harungana madagascariensis
had been tested for its antibacterial effect [43,44], antiparasitic effects
on Entamoeba histolytica[45], and antioxidant properties [46,47]. In vivo
studies were also conducted testing different extracts of Harungana
madagascariensis for their hepatotoxic and nephrotoxic effects [48–50].
In other instances, the studies focused on testing the in vitro anti-
plasmodial activity for a different strain of P. falciparum. For example,
extracts from Abuta grandifolia were tested against both K1 and T9-96
strains [51] as well as the FcB2 strain of Plasmodium falciparum[5].
Another study checked the antiplasmodial effect of a herb in question as
part of a combination with other herbs [52].
These plants/isolated compounds need to be experimented further.
Table 3 represents the list of herbs, with good to very good activity, for
further research as they showed promising potential antiplasmodial
effect need to be further investigated. However, the outcomes of future
experiments might be affected by events observed in the reverse
pharmacology as the case of A. mexicana[16,53–55]. In this case, al-
though the crude extract was proven effective in the clinical trial using
the medicinal herb, the substances claimed to have had in vitro anti-
plasmodial activity could not show the expected antiplasmodial effect.
Thus, it is possible that these selected herbs may not show any desired
antiplasmodial effect during in vivo experiments, with the chance that
they may be deemed useless herbs.
This work is subjected at least to the following limitations. We only
reviewed articles that are accessible online making reporting bias a
possibility as a result of the potential incomplete retrieval and assess-
ment of identified research. Selection bias is also another limitation as
herbs that have traditionally used against malaria and/or its symptoms
have been selected in this systematic review. Publication bias is also a
limiting factor related to researchers on antimalarials because the au-
thors usually prefer to patent their finding before publishing their work
making it possible for some effective medicinal plants to be identified as
effective but the work is still not published yet. Articles that are not in
M.T. Lemma et al. Parasitology International 66 (2017) 713–720

Table 3
Assessment of IC50 Final list of herbs for further research as potential antiplasmodials.

Very good activity

Very good activity

Very good activity

Very good activity

Good activity

Good activity

Good activity

Good activity

Good activity
Name of herb Family name Country of availability
valuesa

Piper holtonii C. DC. Moraceae S. America

Brucea javanica (L.) Merr. Simaroubaceae Thailand
Brucea javanica (L.) Merr. Brucea javanica (L.) Merr. Brucea javanica (L.)
Merr.

0.007 ± 0.001 (vs D10) and 0.006 ± 0.002 (vs W2)

Casearia sylvestris var. Flacourtiaceae Central and South
lingua America
Fibraurea tinctoria Lour. Menispermaceae E. Asia
Hyptis suaveolens Lamiaceae Thailand
Nauclea latifolia Rubiaceae Ghana, Gabon, DR
Congo
Quassia africana Simaroubaceae Cameroon, Zaire,
Angola
Strychnos icaja Loganiaceae West tropical Africa
Zanthoxylum rhoifolium Rutaceae S. America
Aspidosperma desmanthum Apocynaceae S. America
0.25 ± 0.07
IC50 (μg/ml)

English have not been included for this systematic review due to the
96 h: 0.3

96 h: 0.3

language barrier. Entirely, we documented 977 plant species studied for

48 h: 1

48 h: 1
0.001

0.018

0.007

their effectiveness for malaria. However, no details are reported for

0.21

0.1

those herbs with no or minimal antiplasmodial activities. Hence, it was

possible to characterize only those plants for which information was
4-Nerolidylcatechol of class Phenylpropanoid/terpenoid from (roots) tested against the
Neosergeolide of class Quassinoid/terpenoid from (roots and stem bark) tested against

Artemisinin extract from herbal tea (leaves) tested against chloroquine (CQ)-sensitive
the Chloroquine, pyrimethamine, and cycloguanil resistant K1 strain of P. falciparum.

available, i.e., 752 species.

Aspidocarpine of class Indole alkaloid from (bark) tested against the Chloroquine,

Chloroquine, pyrimethamine, and cycloguanil resistant K1 strain of P. falciparum.

Abietane-type diterpenoid endoperoxide, 13α-epi-dioxiabiet-8(14)-en-18-ol from
Ellipticine of class Indole alkaloid from (bark) tested against the Chloroquine,

4. Conclusion
(leaves) tested against chloroquine-sensitive D10 strain of P. falciparum.
pyrimethamine, and cycloguanil resistant K1 strain of P. falciparum.

pyrimethamine, and cycloguanil resistant K1 strain of P. falciparum.

The information presented in this systematic review provides evi-

dence for the existence of the traditionally used potentially anti-
plasmodial medicinal plants. The in vitro studies suggest that these
Artemisinin extracts from (leaves) tested against monitored
Gedunin extracts from (bark) tested against P. falciparum.

Gedunin extracts from (bark) tested against P. falciparum.

traditional uses are linked to the presence of good IC50 values. Different
plants such as Harungana madagascariensis, Quassia africana and Brucea
D10 and CQ-resistant W2 strains of P. falciparum.

javanica have been found to have promising crude extracts. Pure com-
Good activity: IC50 = 0.1–1 μg/ml; moderate activity: IC50 > 1–5 μg/ml; and inactive: IC50 > 5 μg/ml. ND; no data.

pounds with very good antiplasmodial effect have also been isolated
chloroquine-sensitive strain of P. falciparum.
List of plants (herbs with pure compounds) with very good to good antiplasmodial activities based on IC50 values.

from Picrolemma spruce, Aspidosperma vargasi, Artemisia annua, and

Aspidosperma desmanthum. Still very limited number of ethnomedicinal
plants have been assessed compared with the vast number of naturally
existing plants. Evidently, it is the time to increase laboratory-based
studies. In addition, alternative methods such as the reverse pharma-
cology technique need to be implemented in order to ascertain the ef-
fectiveness of traditionally used antiplasmodial plants and their ex-
tracts.
Bioassay model

Supplementary data to this article can be found online at http://dx.

doi.org/10.1016/j.parint.2017.09.002.

Author contributions
May and June

M.T.L., A.M.A., and M.T.E. conceived and designed the study beside
Harvesting

September

participation in all steps. H.T.N., T.L.H., and E.C.A. participated in

season

screening, data extraction, and data presentation. T.K.S., A.S., and S.M.
ND

ND

ND

ND

ND

ND

ND

participated in screening and data extraction. K.N. and K.H. partici-

pated in data presentation and writing. N.T.H. and J.K. participated in
planning, data presentation, writing, and review the manuscript.
Amazonas/Brazil

Amazonas/Brazil

Amazonas/Brazil

Amazonas/Brazil
Region/country

Very good activity: IC50 < 0.1 μg/ml.

Southeastern

South Korea

Disclosure statement
Nigeria
Sudan

Sudan

Italy

The authors state that no competing financial interests exist in this

systematic review.
Pothomorphe peltata[24]
Picrolemma sprucei[24]

Azadirabta indica[65]
Hyptis suaveolens[64]
Aspidosperma vargasii

desmanthum[24]

Mefia azedaracb[65]

Artemisia annua[25]
tricuspidata[61]

Acknowledgements
Name of Herb

Parthenocissus
Aspidosperma

This work was supported in part by a Nagasaki University Institute

[24]

of Tropical Medicine–Kenya Medical Research Institute

Table 2

(NUTIM–KEMRI) Project, Nairobi, Kenya for Kenji Hirayama and a

a

“Grant-in-Aid for Scientific Research (B)” (16H05844, 2016–2019 for

718
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