Skip to main content
Download PDF

Antiplasmodial, antimalarial activities and toxicity of African medicinal plants: a systematic review of literature

Malaria Journal volume 20, Article number: 349 (2021) Cite this article

Abstract

Background

Malaria still constitutes a major public health menace, especially in tropical and subtropical countries. Close to half a million people mainly children in Africa, die every year from the disease. With the rising resistance to frontline drugs (artemisinin-based combinations), there is a need to accelerate the discovery and development of newer anti-malarial drugs. A systematic review was conducted to identify the African medicinal plants with significant antiplasmodial and/or anti-malarial activity, toxicity, as wells as assessing the variation in their activity between study designs (in vitro and in vivo).

Methods

Key health-related databases including Google Scholar, PubMed, PubMed Central, and Science Direct were searched for relevant literature on the antiplasmodial and anti-malarial activities of African medicinal plants.

Results

In total, 200 research articles were identified, a majority of which were studies conducted in Nigeria. The selected research articles constituted 722 independent experiments evaluating 502 plant species. Of the 722 studies, 81.9%, 12.4%, and 5.5% were in vitro, in vivo, and combined in vitro and in vivo, respectively. The most frequently investigated plant species were Azadirachta indica, Zanthoxylum chalybeum, Picrilima nitida, and Nauclea latifolia meanwhile Fabaceae, Euphorbiaceae, Annonaceae, Rubiaceae, Rutaceae, Meliaceae, and Lamiaceae were the most frequently investigated plant families. Overall, 248 (34.3%), 241 (33.4%), and 233 (32.3%) of the studies reported very good, good, and moderate activity, respectively. Alchornea cordifolia, Flueggea virosa, Cryptolepis sanguinolenta, Zanthoxylum chalybeum, and Maytenus senegalensis gave consistently very good activity across the different studies. In all, only 31 (4.3%) of studies involved pure compounds and these had significantly (p = 0.044) higher antiplasmodial activity relative to crude extracts. Out of the 198 plant species tested for toxicity, 52 (26.3%) demonstrated some degree of toxicity, with toxicity most frequently reported with Azadirachta indica and Vernonia amygdalina. These species were equally the most frequently inactive plants reported. The leaves were the most frequently reported toxic part of plants used. Furthermore, toxicity was observed to decrease with increasing antiplasmodial activity.

Conclusions

Although there are many indigenous plants with considerable antiplasmodial and anti-malarial activity, the progress in the development of new anti-malarial drugs from African medicinal plants is still slothful, with only one clinical trial with Cochlospermum planchonii (Bixaceae) conducted to date. There is, therefore, the need to scale up anti-malarial drug discovery in the African region.

Background

Malaria still constitutes a major public health menace, especially in tropical and subtropical countries. Various species of Plasmodium, transmitted through the bite of an infected female Anopheles mosquito, cause malaria, including Plasmodium falciparum, Plasmodium malariae, Plasmodium ovale, Plasmodium vivax, and Plasmodium knowlesi. Among these species, P. falciparum is the most virulent, responsible for the highest morbidity and mortality. It is also the predominant species in sub-Saharan Africa (SSA), a region with the highest number of malaria cases and deaths in the world. According to the World Health Organization (WHO), there were 228 million cases, and 405,000 malaria attributed deaths in 2018 [1]. In SSA, children and pregnant women are the most at-risk groups [1,2,3].

Malaria can be treated using chemotherapy but there is widespread resistance to many of the drugs. The first case of resistance to artemisinins was reported in Cambodia in 2006 and has then spread to most of South-East Asia [4, 5]. The safety of chemoprophylaxis is also a major concern; for instance, primaquine, atovaquone, and doxycycline are contraindicated in pregnant women and children [6]. All these shortcomings necessitate the discovery and production of new drugs to treat malaria.

In the past 50 years, natural compounds including plant products, have played a major role in drug discovery and have provided value to the pharmaceutical industry [7]. For instance, therapeutics for various infectious diseases, cancer, and other debilitation diseases caused by metabolic disorders have all benefitted from many drug classes that were initially developed based on active compounds from plant sources [8]. Furthermore, quinine and artemisinin, and their synthetic derivatives which are the mainstay of anti-malarial chemotherapy, were also derived from plant sources. In malaria-endemic areas, especially in Africa, many people rely on herbal medicines as the first line of treatment [9]. The common reasons for their preference vary from the cost of standard drugs, availability and accessibility, perceived effectiveness, low side effect, and faith in traditional medicines [10].

Reviews of the antiplasmodial and anti-malarial activities of medicinal plants are needed to drive research into the discovery and production of new anti-malarial drugs. Only a few reviews of the antiplasmodial or anti-malarial activity of medicinal plants have been published in the scientific literature [11,12,13,14,15,16]. These reviews focused only on studies with high antiplasmodial or anti-malarial activity and hardly report on their toxicity. The purpose of this study was to review medicinal plants with moderate to very good antiplasmodial and anti-malarial activities, as well as assess the variation in the activities between different methods. Furthermore, the toxicity of plant species is highlighted.

Methods

The literature was reviewed in search of scientific articles reporting antiplasmodial activities (IC50, ED50, LD50, and parasite suppression rate) of medicinal plants used in Africa to treat malaria. The current study conforms to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines [17].

Search strategy and selection criteria

Relevant articles were searched in health-related electronic databases including PubMed, PubMed Central, Google Scholar, and ScienceDirect using the keywords: Traditional herbs or Medicinal plants or Antiplasmodial activity or Antimalarial activity or Herbal medicine or Plasmodium.

The search was limited to studies published in English or containing at least an abstract written in English until May 2020. The titles and abstracts were subsequently examined by two reviewers, independently (parallel method) to identify articles reporting the antiplasmodial activity of medicinal plants. In the case of any discrepancy in their reports, a third reviewer was brought in to resolve the issue. Relevant papers were equally manually cross-checked to identify further references. The following data were extracted from the selected articles by the reviewers: plant species, plant family, place of collection of plant, parts of the plant used, type of study (whether in vitro, in vivo, or human), the extraction solvent used, IC50 or ED50 values, parasite suppression rate, isolated compounds, interaction with known malarial drugs (whether synergistic or antagonistic), and toxicity. Articles that did not report antiplasmodial or anti-malarial activity of medicinal plants as well as review articles were excluded. The entire selection process is presented in Fig. 1.

Fig. 1
figure 1

Flowchart of the selection process for publications included in this review

Full size image

In this study, antiplasmodial activity pertains to studies performed in vitro using different strains of Plasmodium falciparum, meanwhile, anti-malarial activity is reserved for in vivo studies performed using mice and various parasite models (including Plasmodium berghei, Plasmodium yoelii, and Plasmodium chabaudi) and reporting parasite suppression rate.

Categorization of antiplasmodial and anti-malarial activities

For in vitro studies, the antiplasmodial activity of an extract was considered very good if IC50 < 5 µg/ml, good 5 µg/ml ≤ IC50 < 10 µg/ml, and moderate 10 µg/ml ≤ IC50 < 20 µg/ml [18]. For in vivo studies, the anti-malarial activity of an extract is considered very good if the suppression is ≥ 50% at 100 mg/kg body weight/day, good if the suppression is ≥ 50% at 250 mg/kg body weight/day, and moderate if the suppression is ≥ 50% at 500 mg/kg body weight/day [18]. Antiplasmodial activities of 20 µg/ml and above for in vitro studies and anti-malarial ≥ 50% at > 500 mg/kg body weight/day for in vivo studies, were considered inactive.

Risk of bias in individual studies

The level of risk of bias for the study was likely to be high mainly because of differences in the studies and the methods used to determine the antiplasmodial or anti-malarial activity. The stains of Plasmodium used to assess the antiplasmodial or anti-malarial activity of the medicinal plants equally varied between studies. Furthermore, the extraction solvent, as well as the extraction yield of the plants in the different studies, was not the same, which may have accounted for the variation in the antiplasmodial and anti-malarial activities for the same plants but in the different studies.

Results

The PRISMA flowchart (Fig. 1) presents a four-phase study selection process in the present systematic review study. A total of 25,159 titles were identified in the initial search. After the title and abstract screening, 228 full-text articles were retrieved. Of these, a final 200 articles were identified for the review.

For this review, the evaluation of the individual plant species was considered as an independent study, so it is common for one article to have more than one study depending on the number of plant species evaluated. In all, there were 722 independent studies. Five hundred and ninety-on (81.9%) of the independent studies were in vitro (Table 1), 90 (12.4%) were in vivo (Table 2) and 40 (5.5%) were both in vitro and in vivo (Table 3). There was only one human study (clinical trial) conducted so far (Table 4). The selected research articles were from 31 African countries. Out of the 200 research articles reviewed, most of them were from Nigeria 58 (29.0%), Kenya 24 (12.0%), Ethiopia 13 (6.5%), Cameroon 12 (6.0%), Ivory Coast 11 (5.5%), D.R. Congo 10 (5.0%), and Burkina Faso 7 (3.5%) (Fig. 2). The studies cover the period from 1989 to 2020.

Table 1 In vitro antiplasmodial activity of African medicinal plants
Full size table
Table 2 In vivo antimalarial activity of African medicinal plants
Full size table
Table 3 In vitro and in vivo studies on African medicinal plants
Full size table
Table 4 Clinical trial on African medicinal plants
Full size table
Fig. 2
figure 2

Distribution of the research articles on the antiplasmodial activity of indigenous plants according to African countries

Full size image

Family and species distribution of plants evaluated

From 722 studies, the most frequent plant families studied included Fabaceae 47 (6.5%), Euphorbiaceae 45 (6.2%), Annonaceae 37 (5.1%), Rubiaceae 37 (5.1%), Rutaceae 37 (5.1%), Meliaceae 30 (4.2%), and Lamiaceae 12 (1.7%). Five hundred and two (502) plant species were investigated in this study. Of them, the most investigated were: Azadirachta indica, Zanthoxylum chalybeum, Picrilima nitida, and Nauclea latifolia. The most frequent parts of the plants tested were the leaves, roots, root barkss, stems, and the whole plant. A majority of the studies used the crude extracts of the plants compared to pure compounds (95.7% vs. 4.3%). In descending order, methanol 322 (44.7%), dichloromethane 207 (28.7%), ethanol 103 (14.3%), water 85 (11.7%) and ethyl acetate 62 (8.6%) were the most frequent extraction solvent used.

In vitro and in vivo activities of the plants evaluated

Overall, 248 (34.3%) of the studies reported activity that was very good (IC50 values < 5 µg/ml or suppression rate of ≥ 50% at 100 mg/kg body weight/day), 241 (33.4%) reported good activity and 233 (32.3%) reported moderate activity. For the in vitro studies, a majority 228 (38.6%) reported very good activity; 206 (34.9%) reported good activity and 187 (31.6%) reported moderate activity. Meanwhile for the in vivo studies, a majority 19 (21.1%) reported moderate activity, 16 (17.8%) reported very good activity and 13 (14.4%) reported good activity. For studies reporting both the in vitro and in vivo activity, a majority of 17 (42.5%) reported only moderate activity, 13 (32.5%) studies reported very good activity and 10 (25.0%) reported good activity. Among the plants with very good activity, only one species demonstrated very good activity both in vitro and in vivo (Table 3).

Among the studies, the most frequent plant species demonstrating very good antiplasmodial activity were: Alchornea cordifolia [3/3, 100%], Flueggea virosa [3/3, 100%], Cryptolepis sanguinolenta [¾, 75%], Zanthoxylum chalbeum [4/5, 80%] and Maytenus senegalensis [3/6, 50%]. Plant families with the most active species include Rutaceae [13/25, 52.0%], Apocynaceae [13/26, 50%], Celastraceae [7/15, 46.7%], Annonaceae [17/37, 45.9%], Euphorbiaceae [21/48, 43.8], Combretaceae [7/16, 43.8%], Fabaceae [18/47, 38.3%], Lamiaceae [8/23, 34.8%], Asteraceae [23/69, 33.3%], and Rubiaceae [8/37, 21.6%]. The fractions are derived from the count of studies reporting very good antiplasmodial activity (numerator) divided by the total number of studies that assessed the activity of that plant species (denominator).

Azadirachta indica and Vernonia amygdalina were the most frequently reported inactive species (Additional file 1: Table S1). Furthermore, Fabaceae, Rubiaceae, Euphorbiaceae, and Asteraceae were the plant families containing the most frequently reported inactive plants. A majority of 95.7% (691/722) of the studies used the crude extract of the plants. The antiplasmodial and/or anti-malarial activity was significantly higher (p = 0.044) in studies using pure compounds compared to those using crude preparations.

Toxicity of plants evaluated for their antiplasmodial and anti-malarial activity

Out of the 198 plants evaluated in toxicity assays, 52 (26.3%) were found to demonstrate some degree of toxicity. The most frequently reported plants with toxicity were Azadirachta indica and Vernonia amygdalina. Plant families harboring the most toxic species were Lamiaceae, Anacardiaceae, Moraceae, Meliaceae, Asteraceae, and Fabaceae. Approximately 33% of the plants tested demonstrated some toxicity in vitro and 26.7% had some degree of toxicity in vivo. Among plants with very good, good, and moderate antiplasmodial activity, 17.8%, 28.3%, and 35.4% had some degree of toxicity, respectively. The leaf was the plant part with the most frequently reported toxicity. Albino mice and Vero E6 cells were the most commonly used assays for the assessment of the toxicity of the plants.

Discussion

Resistance to the frontline anti-malarial drugs is increasing and is now a global concern. With this rising rate of resistance, there is a need to accelerate research into the discovery and development of new anti-malarial drugs. Unfortunately, from this study, it is evident that the progress into the discovery of a new anti-malarial drug in Africa is slothful. Despite a considerable number of plant species that have demonstrated significant antiplasmodial activity in vitro, fewer plants have been evaluated in vivo and only one clinical trial with Cochlospermum planchonii (Bixaceae) has been conducted so far. This reinforces the need for basic and clinical research in the region. Van Wyk [213] had also arrived at the same conclusion.

This review revealed research articles from 31 African countries. Most of the articles were from Nigeria. This is suggestive that Nigeria is leading the podium in research on anti-malarial drug discovery and development, deservedly so, because she is probably the most affected country in the world. It is noteworthy that South Africa which is generally more technologically advanced than Nigeria had very few (8) articles. The African region is the most affected in the world recording the greatest number of cases and malaria attributed deaths. However, the distribution of malaria in Africa is not even, with sub-Saharan Africa harboring disproportionately the greatest number of cases. This is suggestive that research to identify new anti-malarial drugs may be related to the burden of the disease, thus the government policy to control the disease. There is, therefore, the need for policy-driven research into new anti-malarial all across the African region. In this review, IC50 values of < 20 µg/ml were considered as the cutoff of significant anti-malarial activity. This cutoff is considered the minimum to qualify as a first-pass “hit” in anti-malarial drugs screening [214]. Five hundred and two (502) plant species from 169 families were observed to have moderate to very good anti-malarial activity. The most investigated plant families were Euphorbiaceae, Fabaceae, Rubiaceae, and Annonaceae. However, the plant families containing the most active plants were Apocynaceae, Celestraceae, and Rutaceae. This finding suggests that more emphasis should be given to plants in these families for anti-malarial drug discovery. Besides, the most investigated plant species were Azadirachta indica, Nauclea latifolia, Picralima nitida, and Zanthoxylum chalybeum. Alchornea cordifolia, Flueggea virosa, Crytolepis sanguinolenta, and Zanthoxylum chalybeum were the only plant species with consistently very good antiplasmodial and anti-malarial activities between studies. This is very surprising that no clinical trial using any of these plants has been conducted. Further studies on these plant species should be performed.

This study revealed that overall, a majority of the plants investigated had very good antiplasmodial activity in vitro. That activity decreases as you move to in vivo in most studies, with a majority of plants demonstrating only moderate activity. For example, Gathirwa et al. [146] showed that the activity of Uvaria acuminate decreased from good activity in vitro to inactive in vivo. However, a few studies show that plant activity could also increase from in vitro to in vivo. For example, Ngbolua et al. [211] showed that the activity of Vernonia ambigua increased from in vitro to in vivo analysis. Other examples include studies by Muthaura et al. [20] using Boscia angustifolia, Kweyamba et al. [162] using Commiphora Africana, and Ajaiyeoba et al. [204] using Annona senegalensis. This suggests that plants could still have significant anti-malarial activity in vivo although they failed to in vitro. Most investigators usually progress to in vivo studies only when they observe significant antiplasmodial activity in vitro. This may explain the findings of a smaller number of in vivo studies in the current study. The investigation of the anti-malarial activities of plants should continue in vivo despite the dismal performance of the plants in vitro.

The current study revealed substantial inter-study variation in the antiplasmodial activity of several plant species. For example, considerable variation in the antiplasmodial activity was observed for Senna occidentalis, Adansonia digitata, Acanthospermum hispidum, Rotheca myricoides, Anogeissus leocarpus, Annona muricata, Ageratum conyzoides, Albizia coriaria, Ekebergia capensis, Flueggea virosa, Lippia javanica, Maytenus senegalensis, Morinda lucida, Picralima nitida, Trichilia emetica, Vernonia amydalina, and Vernonia colorata. The factors that could have accounted for these differences may include differences in the extraction solvent thus the extraction yield and extracted metabolite. With dichloromethane, mainly the apolar metabolites are extracted. In contrast, with methanol, from polar to moderate apolar metabolites are extracted.

Most (95.7%) of the studies used crude extract for their investigation and rarely the pure compounds (Additional file 1: Table S2 presents a summary of active compounds that have been identified from some of the plants). The finding of a majority of studies in Africa using only the crude extract of plants may be attributed to the absence of the necessary infrastructure to process the plant materials to get the pure compounds. Furthermore, there may be geographical differences in the areas where the plants were collected and this may also affect the activity of the same plant species. For example, despite using the same extraction solvent, the antiplasmodial activity of Acacia nilotica was moderate in South Africa and very good in Sudan. There was also variation between the different assay types. For example, the activities of Vernonia ambigua [211] and Annona senegalensis [204] have been reported to increase from inactive in vitro to very good in vivo. However, a few plant species including Alchornea cordifolia, and Zanthoxylum chalybeum, were observed to be consistently very good between studies. These plant species should be exploited further for their antiplasmodial activity. The activities of the plants were equally observed to increase with the isolation of the active compounds thus reinforcing the need for research into identifying the active compounds of African medicinal plants. The marked difference in the antiplasmodial activity of the crude extract of Artemisia annua and the pure compounds points out the issue that even the compounds which show only low potency and may be discarded from the initial screen for further development may still have active components with therapeutic potential [215]. The strain of the Plasmodium used may also be another factor accounting for the inter-study variation observed; studies using chloroquine-sensitive strains of the parasite like P. falciparum 3D7, D6, NF54 tend to report higher antiplasmodial activity compared to studies using chloroquine-resistant strains like P. falciparum W2, Dd5, K1 or D10.

This study revealed that only a few (26.3%) of the plants demonstrated some degree of toxicity. The families hosting the most toxic plant species were Lamiaceae, Anacardiaceae, Moraceae, and Meliaceae. The most toxic plants were Azadirachta indica and Vernonia amygdalina. The former [168] is one of the few plant species that demonstrated very good antiplasmodial activity in some studies. Other plants with high toxicity but very good antiplasmodial/anti-malarial activities include Arenga engleri [25], Celtis integrifolia [52], Ficus platyhylla [50], Gutenbergia cordifolia [21], Helchrysum cymosum [97], Microglossa pyrifolia [92], Opilia celtidifolia [52], Quassia Africana [103], Rumex abyssinicus [92], Clausena anisota [157], Icacina senegalensis [171], Abutilon grandiflorum [200], and Lannea schweinfurthii [205]. The isolation of the active compounds, which has to be done, could eliminate the toxicity, if not all, to a certain degree. For example, Salvia radula crude extract (of aerial parts) has been shown to demonstrate some degree of toxicity, but betulafolientriol oxide isolated from the plant was very active with little or no toxicity against human kidney epithelial cells [120]. There was also considerable variation in the toxicity between the assay types (in vitro or in vivo). As many as 32.8% of the plants demonstrated some level of toxicity in vitro meanwhile 26.7% were toxic in vivo. Since it is customary to evaluate toxicity at the in vitro level and toxic plants are discarded before in vivo evaluation, that may explain while fewer plants were toxic in vivo. Toxicity varied within the same plant species from study to study and could be attributed to differences in the study design as well as differences in the parts of the plants used for testing. From this study, the most toxicity was observed with the leaves. Also, a relationship could be established between toxicity and antiplasmodial activity; as the activity of the plant increases, the toxicity, on the other hand, was observed to decrease. Furthermore, albino mice and Vero E6 cells were the most commonly used assays in the evaluation of toxicity. Unfortunately, the authors could nt make a meaningful relationship between the type of assay and toxicity because of the fewer studies assessing the toxicity of the medicinal plants.

This study, however, is limited in that the analyses may have been compounded by the substantial inter-study variation in the methodologies used by different independent studies for the extraction of plant material, the overall extraction yield, the diversity of extracted metabolites as well as the geographical variations in the different sites used in the plant collection. However, the study has provided important baseline data that may be exploited by researchers in the field for the discovery and development of new anti-malarial drugs.

Conclusion

This study has revealed the slothful progress in the discovery and development of new anti-malarial drugs from African medicinal plants. Despite the encouraging activities demonstrated by the plants in vitro, fewer plants have been evaluated in vivo and just one clinical trial has been conducted so far with Cochlospermum planchonii (Bixaceae). The study also revealed considerable inter-study variation in the antiplasmodial activities of the plants, however, the activity of some plants including Alchornea cordifolia, Azadirachta indica, and Zanthoxylum chalybeum was consistently very good. The study demonstrates a relationship between antiplasmodial activity and toxicity whereby the toxicity of the plants decreases as the antiplasmodial activity increases. Besides, the active compounds were identified in just a handful of the plants. Therefore, there is a need for a policy-driven approach in the discovery and development of new anti-malarial drugs to subvert the rising resistance to the frontline anti-malarial drugs in the world.

Availability of data and materials

Not applicable.

Abbreviations

PRISMA:

Preferred Reporting Items for Systematic Reviews and Meta-analysis

Nd:

Not done

Ns:

Not specified

SI:

Selectivity Index

LD50 :

Median lethal dose

IC50 :

Half-maximal inhibitory concentration

CC50 :

50% Cytotoxic concentration

LC50 :

Lethal concentration

References

  1. WHO. World malaria report 2019. Geneva: World Health Organization; 2019. Accessed on 28/06/2021 at https://www.who.int/publications-detail/world-malaria-report-2019.

  2. Kwenti ET. Malaria and HIV coinfection in sub-Saharan Africa: prevalence, impact, and treatment strategies. Res Rep Trop Med. 2018;9:123–36.

    PubMed  PubMed Central  Google Scholar 

  3. Kwenti ET, Kukwah TA, Kwenti TDB, Nyassa BR, Dilonga MH, Enow-Orock G, et al. Comparative analysis of IgG and IgG subclasses against Plasmodium falciparum MSP-119 in children from five contrasting bioecological zones of Cameroon. Malar J. 2019;18:16.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Dondorp AM, Nosten F, Yi P, Das D, Phyo AP, Tarning J, et al. Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2009;361:455–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Murray CJ, Rosenfeld LC, Lim SS, Andrews KG, Foreman KJ, Haring D, et al. Global malaria mortality between 1980 and 2010: a systematic analysis. Lancet. 2012;379:413–31.

    Article  PubMed  Google Scholar 

  6. Nagendrappa PB, Annamalai P, Naik M, Mahajan V, Mathur A, Susanta G, et al. A prospective comparative field study to evaluate the efficacy of a traditional plant-based malaria prophylaxis. J Intercult Ethnopharmacol. 2017;6:36–41.

    Article  PubMed  Google Scholar 

  7. Newman DJ, Cragg GM. Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod. 2012;75:311–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Cragg GM, Grothaus PG, Newman DJ. Impact of natural products on developing new anti-cancer agents. Chem Rev. 2009;109:3012–43.

    Article  CAS  PubMed  Google Scholar 

  9. Willcox ML. A clinical trial of “AM”, a Ugandan herbal remedy for malaria. J Public Health Med. 1999;21:318–24.

    Article  CAS  PubMed  Google Scholar 

  10. Suswardany DL, Sibbritt DW, Supardi S, Pardosi JF, Chang S, Adams J. A cross-sectional analysis of traditional medicine use for malaria alongside free antimalarial drugs treatment amongst adults in high-risk malaria endemic provinces of Indonesia. PLoS One. 2017;12:e0173522.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Ibrahima HA, Imama IA, Bellob AM, Umara U, Muhammada S, Abdullahia SA. The potential of Nigerian medicinal plants as antimalarial agent: a review. Int J Sci Technol. 2012;2:600–5.

    Google Scholar 

  12. Zofou D, Kuete V, Titanji VPK. Antimalarial and other antiprotozoal products from African Medicinal plants. In: Medicinal plant research in Africa: pharmacology and chemistry. Kuete V, Ed. Chapt. 17. Amsterdam, Elsevier, 2013;661–709.

  13. Lawal B, Shittu OK, Kabiru AY, Jigam AA, Umar MB, Berinyuy EB, et al. Potential antimalarials from African natural products: a review. J Intercult Ethnopharmacol. 2015;4:318–43.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Van Wyk BE. A review of commercially important African medicinal plants. J Ethnopharmacol. 2015;176:118–34.

    Article  PubMed  Google Scholar 

  15. Kaur R, Kaur H. Plant derived antimalarial agents. J Med Plants Studies. 2017;5:346–63.

    Google Scholar 

  16. Lemma MT, Ahmed AM, Elhady MT, Ngo HT, Vu TL, Sang TK, et al. Medicinal plants for in vitro antiplasmodial activities: a systematic review of literature. Parasitol Int. 2017;66:713–20.

    Article  PubMed  Google Scholar 

  17. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement. PLoS Med. 2009;6:1000097.

    Article  Google Scholar 

  18. Deharo E, Bourdy G, Quenevo C, Munoz V, Ruiz G, Sauvain M. A search for natural bioactive compounds in Bolivia through multidisciplinary approach. Part V. Evaluation of the antimalarial activity of plants used by the Tacana Indians. J Ethnopharmacol. 2001;77:91–8.

    Article  CAS  PubMed  Google Scholar 

  19. Becker JVW, van der Merwe MM, van Brummelen AC, Pillay P, Crampton BG, Mmutlane EM, et al. In vitro anti-plasmodial activity of Dicoma anomala subsp gerrardii (Asteraceae): identification of its main active constituent, structure-activity relationship studies, and gene expression profiling. Malar J. 2011;10:295.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Gessler MC, Nkunya MH, Mwasumbi LB, Heinrich M, Tanner M. Screening Tanzanian medicinal plants for antimalarial activity. Acta Trop. 1994;56:65–77.

    Article  CAS  PubMed  Google Scholar 

  21. Koch A, Tamez P, Pezzuto J, Soejarto D. Evaluation of plants used for antimalarial treatment by the Maasai of Kenya. J Ethnopharmacol. 2005;101:95–9.

    Article  CAS  PubMed  Google Scholar 

  22. Clarkson C, Maharaj VJ, Crouch NR, Grace OM, Pillay P, Matsabisa MG, et al. In vitro antiplasmodial activity of medicinal plants native to or naturalised in South Africa. J Ethnopharmacol. 2004;92:177–91.

    Article  PubMed  Google Scholar 

  23. El Tahir A, Satti GM, Khalid SA. Antiplasmodial activity of selected Sudanese medicinal plants with emphasis on Maytenus senegalensis (Lam.) Exell. J Ethnopharmacol. 1999;64:227–33.

    Article  PubMed  Google Scholar 

  24. Muthaura CN, Keriko JM, Mutai C, Yenesew A, Gathirwa JW, Irungu BN, et al. Antiplasmodial potential of traditional phytotherapy of some remedies used in treatment of malaria in Meru-Tharaka Nithi County of Kenya. J Ethnopharmacol. 2015;175:315–23.

    Article  CAS  PubMed  Google Scholar 

  25. Prozesky EA, Meyer JJ, Louw AI. In vitro antiplasmodial activity and cytotoxicity of ethnobotanically selected South African plants. J Ethnopharmacol. 2001;76:239–45.

    Article  CAS  PubMed  Google Scholar 

  26. Muthaura CN, Keriko JM, Mutai C, Yenesew A, Gathirwa JW, Irungu BN, et al. Antiplasmodial potential of traditional antimalarial phytotherapy remedies used by the Kwale community of the Kenyan Coast. J Ethnopharmacol. 2015;170:148–57.

    Article  CAS  PubMed  Google Scholar 

  27. Sanon S, Ollivier E, Azas N, Mahiou V, Gasquet M, Ouattara CT, et al. Ethnobotanical survey and in vitro antiplasmodial activity of plants used in traditional medicine in Burkina Faso. J Ethnopharmacol. 2003;86:143–7.

    Article  CAS  PubMed  Google Scholar 

  28. Zirihi-Guédé N, Mambu L, Guédé-Guina F, Bodo B, Grellier P. In vitro antiplasmodial activity and cytotoxicity of 33 West African plants used for treatment of malaria. J Ethnopharmacol. 2005;98:281–5.

    Article  Google Scholar 

  29. Koukouikila-Koussounda F, Abena AA, Nzoungani A, Mombouli JV, Ouamba JM, Kun J, et al. In vitro evaluation of antiplasmodial activity of extracts of Acanthospermum hispidum DC (Asteraceae) and Ficus thonningii Blume (Moraceae), two plants used in traditional medicine in the Republic of Congo. Afr J Tradit Complement Altern Med. 2012;10:270–6.

    PubMed  PubMed Central  Google Scholar 

  30. Owuor BO, Ochanda JO, Kokwaro JO, Cheruiyot AC, Yeda RA, Okudo CA, et al. In vitro antiplasmodial activity of selected Luo and Kuria medicinal plants. J Ethnopharmacol. 2012;144:779–81.

    Article  CAS  PubMed  Google Scholar 

  31. Malebo HM, Tanja W, Cal M, Swaleh SAM, Omolo MO, Hassanali A, et al. Antiplasmodial, anti-trypanosomal, anti-leishmanial and cytotoxicity activity of selected Tanzanian medicinal plants. Tanzan J Health Res. 2009;11:226–34.

    CAS  PubMed  Google Scholar 

  32. Annan K, Sarpong K, Asare C, Dickson R, Amponsah KI, Gyan B, et al. In vitro anti-plasmodial activity of three herbal remedies for malaria in Ghana: Adenia cissampeloides (Planch.) Harms., Termina liaivorensis A. Chev, and Elaeis guineensis Jacq. Pharmacognosy Res. 2012;4:225–9.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Lekana-Douki JB, Liabagui SLO, Bongui JB, Zatra R, Lebibi J, Toure-Ndouo FS. In vitro antiplasmodial activity of crude extracts of Tetrapleura tetraptera and Copaifera religiosa. BMC Res Notes. 2011;4:506.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Ahmed EHM, Nour BYM, Mohammed YG, Khalid HS. Antiplasmodial activity of some medicinal plants used in Sudanese fFolk-medicine. Environ Health Insights. 2010;4:1–6.

    Article  PubMed Central  Google Scholar 

  35. Kuria KA, Chepkwony H, Govaerts C, Roets E, Busson R, De Witte P, et al. The antiplasmodial activity of isolates from Ajuga remota. J Nat Prod. 2002;65:789–93.

    Article  CAS  PubMed  Google Scholar 

  36. Lasisi AA, Olayiwola MA, Balogun SA, Akinloye OA, Ojo DA. Phytochemical composition, cytotoxicity and in vitro antiplasmodial activity of fractions from Alafia barteri olive (Hook F. Icon)-Apocynaceae. J Saudi Chem Soc. 2016;20:2–6.

    Article  CAS  Google Scholar 

  37. Bapela MJ, Meyer JJ, Kaiser M. In vitro antiplasmodial screening of ethnopharmacologically selected South African plant species used for the treatment of malaria. J Ethnopharmacol. 2014;156:370–3.

    Article  PubMed  Google Scholar 

  38. Banzouzi JT, Prado R, Menan H, Valentin A, Roumestan C, Mallie M, et al. In vitro antiplasmodial activity of extracts of Alchornea cordifolia and identification of an active constituent: ellagic acid. J Ethnopharmacol. 2002;81:399–401.

    Article  PubMed  Google Scholar 

  39. Mustofa, Valentin A, Benoit-Vical F, Pélissier Y, Koné-Bamba D, Mallié M. Antiplasmodial activity of plant extracts used in West African traditional medicine. J Ethnopharmacol. 2000;73:145–51.

  40. Musuyu Muganza D, Fruth BI, Nzunzu Lami J, Mesia GK, Kambu OK, Tona GL, et al. In vitro antiprotozoal and cytotoxic activity of 33 ethonopharmacologically selected medicinal plants from Democratic Republic of Congo. J Ethnopharmacol. 2012;141:301–8.

    Article  CAS  PubMed  Google Scholar 

  41. Abdissa D, Geleta G, Bacha K, Abdissa N. Phytochemical investigation of Aloe pulcherrima roots and evaluation for its antibacterial and antiplasmodial activities. PLoS ONE. 2017;12:e0173882.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Iyiola OA, Tijani AY, Lateef KM. Antimalarial activity of ethanolic stem barks extract of Alstonia boonei in mice. Asian J Biol Sci. 2011;4:235–43.

    Article  Google Scholar 

  43. Zirihi-Guédé N, N’guessan K, Etien Dibié T, Grellier P. Ethnopharmacological study of plants used to treat malaria, in traditional medicine, by Bete populations of Issia (Côte d’Ivoire). J Pharm Sci Res. 2010;2:216–27.

    Google Scholar 

  44. Lumpu SL, Kikueta CM, Tshodi ME, Mbenza AP, Kambu OK, Mbamu BM, et al. Antiprotozoal screening and cytotoxicity of extracts and fractions from the leaves, stem barks and root barks of Alstonia congensis. J Ethnopharmacol. 2013;148:724–7.

    Article  CAS  PubMed  Google Scholar 

  45. Hout S, Chea A, Bun SS, Elias R, Gasquet M, Timon-David P, et al. Screening of selected indigenous plants of Cambodia for antiplasmodial activity. J Ethnopharmacol. 2006;107:12–8.

    Article  PubMed  Google Scholar 

  46. Lusakibanza M, Mesia G, Tona G, Karemere S, Lukuka A, Tits M, et al. In vitro and in vivo antimalarial and cytotoxic activity of five plants used in Congolese traditional medicine. J Ethnopharmacol. 2010;129:398–402.

    Article  CAS  PubMed  Google Scholar 

  47. Yamthe LRT, Fokou PVT, Mbouna CDJ, Keumoe R, Ndjakou BL, Djouonzo PT, et al. Extracts from Annona muricata L. and Annona reticulata L. (Annonaceae) potently and selectively inhibit Plasmodium falciparum. Medicines (Basel). 2015;2:55–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Ménan H, Banzouzi J-T, Hocquette A, Pélissier Y, Blache Y, Koné M, et al. Antiplasmodial activity and cytotoxicity of plants used in West African traditional medicine for the treatment of malaria. J Ethnopharmacol. 2006;105:131–6.

    Article  PubMed  Google Scholar 

  49. Boyom FF, Fokou PV, Yamthe LR, Mfopa AN, Kemgne EM, Mbacham WF, et al. Potent antiplasmodial extracts from Cameroonian Annonaceae. J Ethnopharmacol. 2011;134:717–24.

    Article  PubMed  Google Scholar 

  50. Shuaibu MN, Wuyep PA, Yanagi T, Hirayama K, Tanaka T, Kouno I. The use of microfluorometric method for activity-guided isolation of antiplasmodial compound from plant extracts. Parasitol Res. 2008;102:1119–27.

    Article  CAS  PubMed  Google Scholar 

  51. Vonthron-Sénécheau C, Weniger B, Ouattara M, Bi FT, Kamenan A, Lobstein A, et al. In vitro antiplasmodial activity and cytotoxicity of ethnobotanically selected Ivorian plants. J Ethnopharmacol. 2003;87:221–5.

    Article  PubMed  Google Scholar 

  52. Sanon S, Gansane A, Ouattara LP, Traore A, OueDRaogo IN, Tiono A, et al. In vitro antiplasmodial and cytotoxic properties of some medicinal plants from western Burkina Faso. Afr J Lab Med. 2013;2:81.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Chukwujekwu JC, van Staden J, Smith P, Meyer JJM. Antibacterial, anti-inflammatory, and antimalarial activities of some Nigerian medicinal plants. S Afr J Bot. 2005;71:316–25.

    Article  Google Scholar 

  54. Kraft C, Jenett-Siems K, Siems K, Jakupovic J, Mavi S, Bienzle U, et al. In vitro antiplasmodial evaluation of medicinal plants from Zimbabwe. Phytother Res. 2003;17:123–8.

    Article  CAS  PubMed  Google Scholar 

  55. Boyom FF, Kemgne EM, Tepongning R, Ngouana V, Mbacham WF, Tsamo E, et al. Antiplasmodial activity of extracts from seven medicinal plants used in malaria treatment in Cameroon. J Ethnopharmacol. 2009;123:483–8.

    Article  PubMed  Google Scholar 

  56. Waako PJ, Katuura E, Smith P, Folb P. East African medicinal plants as a source of lead compounds for the development of new antimalarial drugs. Afr J Ecol. 2007;45:102–6.

    Article  Google Scholar 

  57. Benoit F, Valentin A, Pelissier Y, Diafouka F, Marion C, Kone-Bamba D, et al. In vitro antimalarial activity of vegetal extracts used in West African traditional medicine. Am J Trop Med Hyg. 1996;54:67–71.

    Article  CAS  PubMed  Google Scholar 

  58. El-Tahir A, Satti GM, Khalid SA. Antiplasmodial activity of selected Sudanese medicinal plants with emphasis on Acacia nilotica. Phytother Res. 1999;13:474–8.

    Article  CAS  PubMed  Google Scholar 

  59. MacKinnon S1, Durst T, Arnason JT, Angerhofer C, Pezzuto J, SanchezVindas PE, et al. Antimalarial activity of tropical Meliaceae extracts and Gedunin derivatives. J Nat Prod. 1997;60:336–41.

  60. Connelly MP, Fabiano E, Patel IH, Kinyanjui SM, Mberu EK, Watkins WM. Antimalarial activity in crude extracts of Malawian medicinal plants. Ann Trop Med Parasitol. 1996;90:597–602.

    Article  CAS  PubMed  Google Scholar 

  61. Ngwira KJ, Maharaj VJ, Mgani QA. In vitro antiplasmodial and HIV-1 neutralization activities of root and leaf extracts from Berberis holstii. J Herb Med. 2015;5:30–5.

    Article  Google Scholar 

  62. Jansen O, Angenot L, Tits M, Nicolas JP, De Mol P, Nikiéma JB, et al. Evaluation of 13 selected medicinal plants from Burkina Faso for their antiplasmodial properties. J Ethnopharmacol. 2010;130:143–50.

    Article  PubMed  Google Scholar 

  63. Benoit-Vical F, Soh PN, Saléry M, Harguem L, Poupat C, Nongonierma R. Evaluation of Senegalese plants used in malaria treatment: focus on Chrozophora senegalensis. J Ethnopharmacol. 2008;116:43–8.

    Article  CAS  PubMed  Google Scholar 

  64. Ogunlanaa OO, Kimb H-S, Watayab Y, Olagunjuc JO, Akindahunsid AA, Tan NH. Antiplasmodial flavonoid from young twigs and leaves of Caesalpinia bonduc (Linn) Roxb. J Chem Pharm Res. 2015;7:931–7.

    Google Scholar 

  65. Weniger B, Lagnika L, Vonthron-Sénécheau C, Adjobimey T, Gbenou J, Moudachirou M, et al. Evaluation of ethnobotanically selected Benin medicinal plants for their in vitro antiplasmodial activity. J Ethnopharmacol. 2004;90:279–84.

    Article  PubMed  Google Scholar 

  66. Melariri P, Campbell W, Etusim P, Smith P. Antiplasmodial properties and bioassay-guided fractionation of ethyl acetate extracts from Carica papaya leaves. J Parasitol Res. 2011;2011:104954.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Kayembe JS, Taba KM, Ntumba K, Tshiongo MTC, Kazadi TK. In vitro antimalarial activity of 20 quinones isolated from four plants used by traditional healers in the Democratic Republic of Congo. J Med Plant Res. 2010;4:991–4.

    CAS  Google Scholar 

  68. Ramalhete C, Lopes D, Mulhovo S, Rosário VE, Ferreira MJU. Antimalarial activity of some plants traditionally used in Mozambique. Workshop Plantas Medicinais e Fitoterapêuticas nos Trópicos.IICT /CCCM, 29, 30 e 31 de Outubro de 2008.

  69. Tona L, Cimanga RK, Mesia K, Musuamba CT, De Bruyne T, Apers S, et al. In vitro antiplasmodial activity of extracts and fractions from seven medicinal plants used in the Democratic Republic of Congo. J Ethnopharmacol. 2004;93:27–32.

    Article  CAS  PubMed  Google Scholar 

  70. Gbeassor M, Kossou Y, Amegbo K, de Souza C, Koumaglo K, Denke A. Antimalarial effects of eight African medicinal plants. J Ethnopharmacol. 1989;25:115–8.

    Article  CAS  PubMed  Google Scholar 

  71. Afoulous S, Ferhout H, Raoelison EG, Valentin A, Moukarzel B, Couderc F, et al. Chemical composition and anticancer, antiinflammatory, antioxidant and antimalarial activities of leaf essential oil of Cedrelopsis grevei. Food Chem Toxicol. 2013;56:352–62.

    Article  CAS  PubMed  Google Scholar 

  72. Irungu BN, Rukunga GM, Mungai GM, Muthaura CN. In vitro antiplasmodial and cytotoxicity activities of 14 medicinal plants from Kenya. S Afr J Bot. 2007;73:204–7.

    Article  Google Scholar 

  73. do Céu de Madureira M, Paula Martins A, Gomes M, Paiva J, Proença da Cunha A, do Rosário V. Antimalarial activity of medicinal plants used in traditional medicine in S. Tomé and Prı́ncipe islands. J Ethnopharmacol. 2002;81:23–9.

  74. Rukunga GM, Gathirwa JW, Omar SA, Muregi FW, Muthaura CN, Kirira PG, et al. Anti-plasmodial activity of the extracts of some Kenyan medicinal plants. J Ethnopharmacol. 2009;121:282–5.

    Article  CAS  PubMed  Google Scholar 

  75. Lacroix D, Prado S, Kamoga D, Kasenene J, Namukobe J, Krief S, et al. Antiplasmodial and cytotoxic activities of medicinal plants traditionally used in the village of Kiohima Uganda. J Ethnopharmacol. 2011;133:850–5.

    Article  PubMed  Google Scholar 

  76. Muregi FW, Chhabra SC, Njagi EN, Lang’at-Thoruwa CC, Njue WM, Orago AS, et al. Anti-plasmodial activity of some Kenyan medicinal plant extracts singly and in combination with chloroquine. Phytother Res. 2004;18:379–84.

    Article  CAS  PubMed  Google Scholar 

  77. Adia MM, Emami SN, Byamukama R, Faye I, Borg-Karlson AK. Antiplasmodial activity and phytochemical analysis of extracts from selected Ugandan medicinal plants. J Ethnopharmacol. 2016;186:14–9.

    Article  CAS  PubMed  Google Scholar 

  78. Lamien-Meda A, Kiendrebeogo M, Compaoré M, Meda RN, Bacher M, Koenig K, et al. Quality assessment and antiplasmodial activity of West African Cochlospermum species. Phytochemistry. 2015;119:51–61.

    Article  CAS  PubMed  Google Scholar 

  79. Benoit F, Valentin A, Pélissier Y, Marion C, Dakuyo Z, Mallié M, et al. Antimalarial activity in vitro of Cochlospermum tinctorium tubercle extracts. Trans R Soc Trop Med Hyg. 1995;89:217–8.

    Article  CAS  PubMed  Google Scholar 

  80. Zofou D, Kengne ABO, Tene M. Ngemenya MN, Tane P, Titanji VP. In vitro antiplasmodial activity and cytotoxicity of crude extracts and compounds from the stem barks of Kigelia africana (Lam.) Benth (Bignoniaceae). Parasitol Res. 2011;108:1383–90.

  81. Paulo A, Gomes ET, Houghton PJ. New alkaloids from Cryptolepis sanguinolenta. J Nat Prod. 1995;58:1485–91.

    Article  CAS  Google Scholar 

  82. Kirby GC, Paine A, Warhurst DC, Noamese BK, Phillipson JD. In vitro and in vivo antimalarial activity of cryptolepine, a plant-derived indoloquinoline. Phytother Res. 1995;9:359–63.

    Article  CAS  Google Scholar 

  83. Cimanga K, De Bruyne T, Pieters L, Vlietinck AJ, Turger CA. In vitro and in vivo antiplasmodial activity of cryptolepine and related alkaloids from Cryptolepis sanguinea. J Nat Prod. 1997;60:688–91.

    Article  CAS  PubMed  Google Scholar 

  84. Grellier P, Ramiaramanana L, Millerioux V, Deharo E, Schrével J, Frappier F, et al. Antimalarial activity of cryptolepine and isocryptolepine, alkaloids isolated from Cryptolepis sanguinolenta. Phytother Res. 1996;10:317–21.

    Article  CAS  Google Scholar 

  85. Zofou D, Tematio EL, Ntie-Kang F, Tene M, Ngemenya MN, Tane P, et al. New antimalarial hits from Dacryodes edulis (Burseraceae) - Part I: Isolation, in vitro activity, in silico “drug-likeness” and pharmacokinetic profiles. PLoS ONE. 2013;8:e79544.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Nafuka SN, Mumbengegwi DR. Phytochemical analysis and in vitro anti-plasmodial activity of selected ethnomedicinal plants used to treat malaria associated symptoms in Northern Namibia. Int Sci Technol J Namibia. 2013;2:78–93.

    Google Scholar 

  87. Jansen O, Tits M, Nicolas ALJP, De Mol P, Nikiema J-B, Frédérich M. Anti-plasmodial activity of Dicoma tomentosa (Asteraceae) and identification of urospermal A-15-O-acetate as the main active compound. Malar J. 2012;11:289.

    Article  PubMed  PubMed Central  Google Scholar 

  88. Olasehinde GI, Ojurongbe O, Adeyeba AO, Fagade OE, Valecha N, Ayanda IO, et al. In vitro studies on the sensitivity pattern of Plasmodium falciparum to antimalarial drugs and local herbal extracts. Malar J. 2014;13:63.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  89. Bickii J, Tchouya GRF, Tchouankeu JC, Tsamo E. Antimalarial activity in crude extracts of some Cameroonian medicinal plants. Afr J Tradit Complement Altern Med. 2007;4:107–11.

    Article  Google Scholar 

  90. Liu Y, Murakami N, Ji H, Abreu P, Zhang S. Antimalarial flavonol glycosides from Euphorbiahirta. Pharm Biol. 2007;45:278–81.

    Article  CAS  Google Scholar 

  91. Kaou AM, Mahiou-Leddet V, Hutter S, Aïnouddine S, Hassani S, Yahaya I, et al. Antimalarial activity of crude extracts from nine African medicinal plants. J Ethnopharmacol. 2008;116:74–83.

    Article  PubMed  Google Scholar 

  92. Muganga R, Angenot L, Tits M, Frédérich M. Antiplasmodial and cytotoxic activities of Rwandan medicinal plants used in the treatment of malaria. J Ethnopharmacol. 2010;128:52–7.

    Article  PubMed  Google Scholar 

  93. Traore-Keita F, Gasquet M, Di Giorgio C, Ollivier E, Delmas F, Keita A, et al. Antimalarial activity of four plants used in traditional medicine in Mali. Phytother Res. 2000;14:45–7.

    Article  CAS  PubMed  Google Scholar 

  94. Ancolio C, Azas N, Mahiou V, Ollivier E, Di Giorgio C, Keita A, et al. Antimalarial activity of extracts and alkaloids isolated from six plants used in traditional medicine in Mali and Sao Tome. Phytother Res. 2002;16:646–9.

    Article  CAS  PubMed  Google Scholar 

  95. Nyambati GK, Lagat ZO, Maranga RO, Samuel M, Ozwara H. In vitro anti-plasmodial activity of Rubia cordifolia, Harrizonia abyssinica, Leucas calostachys Olive and Sanchus schweinfurthii medicinal plants. J Appl Pharm Sci. 2013;3:57–62.

    Google Scholar 

  96. Afoulous S, Ferhout H, Raoelison EG, Valentin A, Moukarzel B, Couderc F, et al. Helichrysum gymnocephalum essential oil: chemical composition and cytotoxic, antimalarial and antioxidant activities, attribution of the activity origin by correlations. Molecules. 2011;16:8273–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Van Vuuren SF, Viljoen AM, Van Zyl RL, Van Heerden FR, Baser KHC. The antimicrobial, antimalarial and toxicity profiles of helihumulone, Leaf essential oil and extracts of Helichrysum cymosum (L.) D. Don subsp. cymosum. S Afr J Bot. 2006;72:287–90.

    Article  CAS  Google Scholar 

  98. Boyom FF. Composition and anti-plasmodial activities of essential oils from some Cameroonian medicinal plants. Phytochemistry. 2003;64:1269–75.

    Article  CAS  PubMed  Google Scholar 

  99. Fotie J, Bohle DS, Leimanis ML, Georges E, Rukunga G, Nkengfack AE. Lupeol long-chain fatty acid esters with antimalarial activity from Holarrhena floribunda. J Nat Prod. 2006;69:62–7.

    Article  CAS  PubMed  Google Scholar 

  100. Sarr SO, Perrotey S, Fall I, Ennahar S, Zhao M, Diop YM, et al. Icacina senegalensis (Icacinaceae), traditionally used for the treatment of malaria, inhibits in vitro Plasmodium falciparum growth without host cell toxicity. Malar J. 2011;10:85.

    Article  PubMed  PubMed Central  Google Scholar 

  101. Bickii J, Njifutie N, Foyere JA, Basco LK, Ringwald P. In vitro antimalarial activity of limonoids from Khaya grandifoliola C.D.C. (Meliaceae). J Ethnopharmacol. 2000;69:27–33.

    Article  CAS  PubMed  Google Scholar 

  102. Wube AA, Bucar F, Asres K, Gibbons S, Rattray L, Croft SL. Antimalarial compounds from Kniphofia foliosa roots. Phytother Res. 2005;19:472–6.

    Article  CAS  PubMed  Google Scholar 

  103. Mbatchi SF, Mbatchi B, Banzouzi JT, Bansimba T, Nsonde Ntandou GF, Ouamba JM, et al. In vitro antiplasmodial activity of 18 plants used in Congo Brazzaville traditional medicine. J Ethnopharmacol. 2006;104:168–74.

    Article  CAS  PubMed  Google Scholar 

  104. Oketch-Rabah HA, Dossaji SF, Mberu EK. Antimalarial activity of some Kenyan medicinal plants. Pharm Biol. 1999;37:329–34.

    Article  Google Scholar 

  105. Ramalhete C, da Cruz FP, Mulhovo S, Sousa IJ, Fernandes MX, Prudêncio M, et al. Dual-stage triterpenoids from an African medicinal plant targeting the malaria parasite. Bioorg Med Chem. 2014;22:3887–90.

    Article  CAS  PubMed  Google Scholar 

  106. BenoitVical F, Valentin A, Cournac V, Pélissier Y, Mallié M, Bastide JM. In vitro antiplasmodial activity of stem and root extracts of Nauclea latifolia S.M. (Rubiaceae). J Ethnopharmacol. 1998;61:173–8.

    Article  CAS  Google Scholar 

  107. Mesia K, Cimanga RK, Dhooghe L, Cos P, Apers S, Totté J, et al. Antimalarial activity and toxicity evaluation of a quantified Nauclea pobeguinii extract. J Ethnopharmacol. 2010;131:6.

    Article  Google Scholar 

  108. Gbeassor M, Kedjagni AY, Koumaglo K, de Soma C, Agbo K, Aklikokou K, et al. In vitro antimalarial activity of six medicinal plants. Phytother Res. 1990;4:115–7.

    Article  Google Scholar 

  109. Karim T, Béourou S, Touré AO, Ouattara K, Meité S, Ako A, et al. Antioxidant activities and estimation of the phenols and flavonoids content in the extracts of medicinal plants used to treat malaria in Ivory Coast. Int J Curr Microbiol App Sci. 2015;4:862–74.

    Google Scholar 

  110. Koudouvo K, Karou SD, Ilboudo DP, Kokou K, Essien K, Aklikokou K, et al. In vitro antiplasmodial activity of crude extracts from Togolese medicinal plants. Asian Pac J Trop Med. 2011;4:129–32.

    Article  PubMed  Google Scholar 

  111. Appiah-Opong R, Nyarko AK, Dodoo D, Gyang FN, Koram KA, Ayisi NK. Antiplasmodial activity of extracts of Tridax procumbens and Phyllanthus amarus in in vitro Plasmodium falciparum culture systems. Ghana Med J. 2011;45:143–50.

    CAS  PubMed  PubMed Central  Google Scholar 

  112. Komlaga G, Cojean S, Dickson RA, Mehdi A, Beniddir MA, SuyyaghAlbouz S, et al. Antiplasmodial activity of selected medicinal plants used to treat malaria in Ghana. Parasitol Res. 2016;115:3185–95.

    Article  PubMed  Google Scholar 

  113. Falodun A, Imieje V, Erharuyi O, Ahomafor J, Jacob MR, Khan SI, et al. Evaluation of three medicinal plant extracts against Plasmodium falciparum and selected microganisms. Afr J Tradit Complement Altern Med. 2014;11:142–6.

    Article  PubMed  PubMed Central  Google Scholar 

  114. François G, Aké Assi L, Holenz J, Bringmann G. Constituents of Picralima nitida display pronounced inhibitory activities against asexual erythrocytic forms of Plasmodium falciparum in vitro. J Ethnopharmacol. 1996;54:113–7.

    Article  PubMed  Google Scholar 

  115. Gbedema SY, Bayor MT, Annan K, Wright CW. Clerodane diterpenes from Polyalthia longifolia (sonn.) Thw. Var. Pendula: potential antimalarial agents for drug resistant Plasmodium falciparum infection. J Ethnopharmacol. 2015;169:176–82.

    Article  CAS  PubMed  Google Scholar 

  116. Annan K, Ekuadzi E, Asare C, Sarpong K, Pistorius D, Oberer L, et al. Antiplasmodial constituents from the stem barks of Polyalthia longifolia var pendula. Phytochem Lett. 2015;11:28–31.

    Article  CAS  Google Scholar 

  117. Orwa JA, Ngeny L, Mwikwabe NM, Ondicho J, Jondiko IJ. Antimalarial and safety evaluation of extracts from Toddalia asiatica (L) Lam. (Rutaceae). J Ethnopharmacol. 2013;145:587–90.

    Article  CAS  PubMed  Google Scholar 

  118. Karou D, Dicko MH, Sanon S, Simpore J, Traore AS. Antimalarial activity of Sida acuta Burm. F. (Malvaceae) and Pterocarpus erinaceus Poir. (Fabaceae). J Ethnopharmacol. 2003;89:291–4.

    Article  PubMed  Google Scholar 

  119. Muregi FW, Chhabra SC, Njagi EN, Lang’at-Thoruwa CC, Njue WM, Orago AS, et al. In vitro antiplasmodial activity of some plants used in Kisii, Kenya against malaria and their chloroquine potentiation effects. J Ethnopharmacol. 2003;84:235–9.

    Article  CAS  PubMed  Google Scholar 

  120. Kamatou GPP, Van Zyl RL, Davids H, Van Heerden FR, Lourens ACU, Viljoen AM. Antimalarial and anticancer activities of selected South African Salvia species and isolated compounds from S. radula. S Afr J Bot. 2008;74:238–43.

    Article  CAS  Google Scholar 

  121. Bah S, Jäger AK, Adsersen A, Diallo D, Paulsen BS. Antiplasmodial and GABA(A)-benzodiazepine receptor binding activities of five plants used in traditional medicine in Mali. West Africa J Ethnopharmacol. 2007;110:451–7.

    Article  PubMed  Google Scholar 

  122. Carraz M, Jossang A, Franetich J-F, Siau A, Ciceron L, Hannoun L, et al. A plant-derived morphinan as a novel lead compound active against malaria liver stages. PLoS Med. 2006;3:e513.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  123. Niass O, Sarr SO, Dieye B, Diop A, Diop YM. In vitro assessment of the antiplasmodial activity of three extracts used in local traditional medicine in Saloum (Senegal). Eur Sci J. 2016;12:157–65.

    Google Scholar 

  124. Kigondu EV, Rukunga GM, Keriko JM, Tonui WK, Gathirwa JW, Kirira PG, et al. Anti-parasitic activity and cytotoxicity of selected medicinal plants from Kenya. J Ethnopharmacol. 2009;123:504–9.

    Article  PubMed  Google Scholar 

  125. Gakunju DM, Mberu EK, Dossaji SF, Gray AI, Waigh RD, Waterman PG, et al. Potent antimalarial activity of the alkaloid nitidine, isolated from a Kenyan herbal remedy. Antimicrob Agents Chemother. 1995;39:2606–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Omoregie ES, Pal A, Sisodia B. In vitro antimalarial and cytotoxic activities of leaf extracts of Vernonia amygdalina (Del.). Niger J Basic Appl Sci. 2011;19:121–6.

    Google Scholar 

  127. Shaa KK, Oguche S, Watila IM, Ikpa TF. In vitro antimalarial activity of the extracts of Vernonia amygdalina commonly used in traditional medicine in Nigeria. Sci World J. 2011;6:5–9.

    Google Scholar 

  128. Toyang NJ, Krause MA, Fairhurst RM, Tane P, Bryant J, Verpoorte R. Antiplasmodial activity of sesquiterpene lactones and a sucrose ester from Vernonia guineensis Benth (Asteraceae). J Ethnopharmacol. 2013;147:618–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Goodman CD, Austarheim I, Mollard V, Mikolo B, Malterud KE, McFadden GI, et al. Natural products from Zanthoxylum heitzii with potent activity against the malaria parasite. Malar J. 2016;15:481.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  130. Randrianarivelojosia M, Rasidimanana VT, Rabarison H, Cheplogoi PK, Ratsimbason M, Mulholland DA, et al. Plants traditionally prescribed to treat tazo (malaria) in the eastern region of Madagascar. Malar J. 2003;2:25.

    Article  PubMed  PubMed Central  Google Scholar 

  131. Okokon JE, Augustine NB, Mohanakrishnan D. Antimalarial, antiplasmodial and analgesic activities of root extract of Alchornea laxiflora. Pharm Biol. 2017;55:1022–31.

    Article  PubMed  PubMed Central  Google Scholar 

  132. Alli LA, Adesokan AA, Salawu OA, Akanji MA, Tijani AY. Anti-plasmodial activity of aqueous root extract of Acacia nilotica. Afr J Biochem Res. 2011;5:214–9.

    CAS  Google Scholar 

  133. Jigam AA, Akanya HO, Dauda BEN, Okogun JO. Polygalloyltannin isolated from the roots of Acacia nilotica Del. (Leguminoseae) is effective against Plasmodium berghei in mice. J Med Plant Res. 2010;4:1169–75.

    CAS  Google Scholar 

  134. Adeoye AO, Bewaji CO. Chemopreventive, and remediation effect of Adansonia digitata L Baobab (Bombacaceae) stem barks extracts in mouse model malaria. J Ethnopharmacol. 2018;210:31–8.

    Article  CAS  PubMed  Google Scholar 

  135. Musila MF, Dossaji SF, Nguta JM, Lukhoba CW, Munyao JM. In vivo antimalarial activity, toxicity and phytochemical screening of selected antimalarial plants. J Ethnopharmacol. 2013;146:557–61.

    Article  CAS  PubMed  Google Scholar 

  136. Ukwe VC, Epueke EA, Ekwunife OI, Okoye TC, Akudor GC, Ubaka CM. Antimalarial activity of aqueous extract and fractions of leaves of Ageratum conyzoides in mice infected with Plasmodium berghei. Int J Pharm Sci. 2010;2:33–8.

    Google Scholar 

  137. Rukunga GM, Muregi FW, Tolo FM, Omar SA, Mwitari P, Muthaura CN, et al. The antiplasmodial activity of spermine alkaloids isolated from Albizia gummifera. Fitoterapia. 2007;78:455–9.

    Article  CAS  PubMed  Google Scholar 

  138. Oladosu IA, Balogun SO, Ademowo GO. Phytochemical screening, antimalarial and histopathological studies of Allophylus africanus and Tragia benthamii. Chin J Nat Med. 2013;11:371–6.

    Article  CAS  PubMed  Google Scholar 

  139. Teka T, Bisrat D, Yeshak MY, Asres K. Antimalarial activity of the chemical constituents of the leaves latex of Aloe pulcherrima Gilbert and Sebsebe. Molecules. 2016;21:1415.

    Article  PubMed Central  CAS  Google Scholar 

  140. Akpan EJ, Okokon JE, Etuk IC. Antiplasmodial and antipyretic studies on root extracts of Anthocleista djalonensis against Plasmodium berghei. Asian Pac J Trop Dis. 2012;2:36–42.

    Article  Google Scholar 

  141. Ene AC, Ameh DA, Kwanashie HO, Agomo PU, Atawodi SE. Preliminary in vivo antimalarial screening of petroleum ether, chloroform, and methanol extracts of fifteen plants grown in Nigeria. J Pharmacol Toxicol. 2008;3:254–60.

    Article  Google Scholar 

  142. Christian AG, Mfon AG, Dick EA, David-Oku E, Akpan JL, Chukwuma EB. Antimalarial potency of the leaf extract of Aspilia africana (Pers.) C.D. Adams. Asian Pac J Trop Med. 2012;2:126–9.

    Article  Google Scholar 

  143. Gathirwa JW, Rukunga GM, Mwitari PG, Mwikwabe NM, Kimani CW, Muthaura CN, et al. Traditional herbal antimalarial therapy in Kilifi district. Kenya J Ethnopharmacol. 2011;134:434–42.

    Article  CAS  PubMed  Google Scholar 

  144. Tepongning RN, Mbah JN, Avoulou FL, Jerme MM, Ndanga EKK, Fekam FB. Hydroethanolic extracts of Erigeron floribundus and Azadirachta indica reduced Plasmodium berghei parasitemia in Balb/c mice. Evid Based Complement Alternat Med. 2018;2018:5156710.

    Article  PubMed  PubMed Central  Google Scholar 

  145. Akin-Osanaiye BC, Nok AJ, Ibrahim S, Inuwa HM, Onyike E, Amlabu E, et al. Antimalarial effect of neem leaves and neem stem barks extracts on Plasmodium berghei infected in the pathology and treatment of malaria. Int J Res Biochem Biophy. 2013;3:7–14.

    Google Scholar 

  146. Asrade S, Mengesha Y, Moges G, Gelayee DA. In vivo antiplasmodial activity evaluation of the leaves of Balanites rotundifolia (Van Tiegh) Blatter (Balanitaceae) against Plasmodium berghei. J Exp Pharmacol. 2017;9:59–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Otegbade OO, Ojo JA, Adefokun DI, Abiodun OO, Thomas BN, Ojurongbe O. Ethanol extract of Blighia sapida stem barks show remarkable prophylactic activity in experimental Plasmodium berghei–infected mice. Drug Target Insights. 2017;11:1177392817728725.

    Article  PubMed  PubMed Central  Google Scholar 

  148. Christian AG, Thecla EC, Dick EA, Chile AE, Chimsorom CK, Ckukwu ND, et al. In vivo antiplasmodial activity of Bombax buonopozense root barks aqueous extract in mice infected by Plasmodium berghei. J Tradit Chin Med. 2017;37:431–5.

    Article  Google Scholar 

  149. Muluye AB, Melese E, Adinew GM. Antimalarial activity of 80 % methanolic extract of Brassica nigra (L.) Koch. (Brassicaceae) seeds against Plasmodium berghei infection in mice. BMC Compl Alternative Med. 2015;15:367.

    Article  CAS  Google Scholar 

  150. Eyasu M, Shibeshi W, Gida M. In vivo antimalarial activity of hydromethanolic leaf extract of Calpurnia aurea (Fabaceae) in mice infected with chloroquine-sensitive Plasmodium berghei. Int J Pharmacol. 2013;2:131–42.

    Google Scholar 

  151. Onaku LO, Attama AA, Okore VC, Tijani AY, Ngene AA, Esimone CO. Antagonistic antimalarial properties of pawpaw leaf aqueous extract in combination with artesunic acid in Plasmodium berghei-infected mice. J Vector Borne Dis. 2011;48:96–100.

    CAS  PubMed  Google Scholar 

  152. Tona L, Mesia K, Ngimbi NP, Chrimwami B, Okondahoka, Cimanga K, et al. In vivo antimalarial activity of Cassia Occidentalism, Morinda morindoides and Phyllanthus niruri. Ann Trop Med Parasit. 2001;95:47–57.

  153. Abdulrazak N, Asiya UI, Usman NS, Unata IM, Farida A. Anti-plasmodial activity of ethanolic extract of root and stem bark of Cassia sieberiana DC on mice. J Intercult Ethnopharmacol. 2015;4:96–101.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Adzu B, Abbah J, Vongtau H, Gamaniel K. Studies on the use of Cassia singueana in malaria ethnopharmacy. J Ethnopharmacol. 2003;88:261–7.

    Article  PubMed  Google Scholar 

  155. Jigam AA, Razaq UTA, Egbuta MN. In vivo antimalarial and toxicological evaluation of Chrozophora senegalensis A. Juss (Euphorbiaceae) extracts. J Appl Pharm Sci. 2011;1:90–4.

    Google Scholar 

  156. Ihekwereme CP, Okoye FK, Agu SC, Oli AN. Traditional consumption of the fruit pulp of Chrysophyllum albidum (Sapotaceae) in pregnancy may be serving as an intermittent preventive therapy against malaria infection. Anc Sci Life. 2017;36:191–5.

    Article  PubMed  PubMed Central  Google Scholar 

  157. Okokon JE, Etebong EO, Udobang JA, Essien GE. Antiplasmodial and analgesic activities of Clausena anisate. Asian Pac J Trop Med. 2012;5:214–9.

    Article  PubMed  Google Scholar 

  158. Anato M, Ketema T. Anti-plasmodial activities of Combretum molle (Combretaceae) [Zwoo] seed extract in Swiss albino mice. BMC Res Notes. 2018;11:312.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  159. Kweyamba PA, Zofou D, Efange N, Assob JN, Kitau J, Nyindo M. In vitro and in vivo studies on antimalarial activity of Commiphora africana and Dichrostachys cinerea used by the Maasai in Arusha region. Tanzania Malar J. 2019;18:119.

    Article  PubMed  Google Scholar 

  160. Elufioye TO, Agbedahunsi JM. Antimalarial activities of Tithonia diversifolia (Asteraceae) and Crossopteryx febrifuga (Rubiaceae) on mice in vivo. J Ethnopharmacol. 2004;93:167–71.

    Article  CAS  PubMed  Google Scholar 

  161. Obey JK, Ngeiywa MM, Kiprono P, Omar S, vonWright A, Kauhanen J, et al. Antimalarial activity of Croton macrostachyus stem barks extracts against Plasmodium berghei in vivo. J Pathog. 2018;2018:393854.

    Article  CAS  Google Scholar 

  162. Tona Ngimbi NP, Tsakala M, Mesia K, Cimanga K, Apers S, De Bruyne T, et al. Antimalarial activity of 20 crude extracts from nine African medicinal plants used in Kinshasa Congo. J Ethnopharmacol. 1999;68:193–203.

    Article  PubMed  Google Scholar 

  163. Mzena T, Swai H, Chacha M. Antimalarial activity of Cucumis metuliferus and Lippia kituiensis against Plasmodium berghei infection in mice. Res Rep Trop Med. 2018;9:81–8.

    PubMed  PubMed Central  Google Scholar 

  164. Amelo W, Nagpal P, Makonnen E. Antiplasmodial activity of solvent fractions of methanolic root extract of Dodonaea angustifolia in Plasmodium berghei infected mice. BMC Complement Altern Med. 2014;14:462.

    Article  PubMed  PubMed Central  Google Scholar 

  165. Ogbonna DN, Sokari TG, Agomuoh AA. Antimalarial activities of some selected traditional herbs from South Eastern Nigeria against Plasmodium species. Res J Parasit. 2008;3:25–31.

    Article  Google Scholar 

  166. Gounoue Kamkumo R, Tsakem Nangap JM, Tchokouaha Yamthe LR, Ngueguim Tsofack F, Tsouh Fokou PV, Tchatat Tali MB, et al. Antimalarial activity of the aqueous extract of Euphorbia cordifolia Elliot in Plasmodium berghei-infected mice. Asian Pac J Trop Med. 2020;13:176–84.

    Article  CAS  Google Scholar 

  167. Oluwakanyinsola AS, Adeniyi YT, Babayi H, Angela CN, Anagbogu RA, Agbakwuru VA. Antimalarial activity of ethanolic stem barks extract of Faidherbia albida (Del) a Chev (Mimosoidae) in mice. Arch Appl Sci Res. 2010;2:261–8.

    Google Scholar 

  168. Nguta JM, Mbaria JM. Brine shrimp toxicity and antimalarial activity of some plants traditionally used in treatment of malaria in Msambweni district of Kenya. J Ethnopharmacol. 2013;148:988–92.

    Article  CAS  PubMed  Google Scholar 

  169. Oluwatosin A, Tolulope A, Ayokulehin K, Okorie P, Aderemi K, Falade C, et al. Antimalarial potential of kolaviron, a biflavonoid from Garcinia kola seeds, against Plasmodium berghei infection in Swiss albino mice. Asian Pac J Trop Med. 2014;7:97–104.

    Article  CAS  PubMed  Google Scholar 

  170. Okokon JE, Ita BN, Udokpoh AE. The in vivo antimalarial activities of Uvariae chamae and Hippocratea africana. Ann Trop Med Parasitol. 2006;100:585–90.

    Article  CAS  PubMed  Google Scholar 

  171. David-Oku E, Ifeoma OO, Christian AG, Dick EA. Evaluation of the antimalarial potential of Icacina senegalensis Juss (Icacinaceae). Asian Pac J Trop Med. 2014;7:S469–72.

    Article  Google Scholar 

  172. Birru EM, Geta M, Gurmu AE. Antiplasmodial activity of Indigofera spicata root extract against Plasmodium berghei infection in mice. Malar J. 2017;16:198.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  173. Onyeto CA, Akah PA, Nworu CS, Okoye TC, Okorie NA, Mbaoji FN, et al. Anti-plasmodial and antioxidant activities of methanol extract of the fresh leaves of Lophira lanceolata (Ochnaceae). Afr J Biotechnol. 2014;13:1731–8.

    Article  Google Scholar 

  174. Christian AG, Akanimo EG, Ahunna AG, Nwakaego EM, Chimsorom CK. Antimalarial potency of the methanol leaf extract of Maerua crassifolia Forssk (Capparaceae). Asian Pac J Trop Dis. 2014;4:35–9.

    Article  PubMed Central  Google Scholar 

  175. Malebo HM, Tanja W, Cal M, Swaleh SAM, Omolo MO, Hassanali A, et al. Antiplasmodial, anti-trypanosomal, anti-leishmanial and cytotoxicity activity of selected Tanzanian medicinal plants. Tanzan J Health Res. 2015;4:226–34.

    Google Scholar 

  176. Okafor AI, Nok AJ, Inuwa HM. Antiplasmodial activity of aqueous leaf extract of Mucuna Pruriens Linn in mice infected with Plasmodium berghei (NK-65 Strain). J Appl Pharm Sci. 2013;3(4 Suppl 1):S52–5.

    Google Scholar 

  177. Edagha IA, Peter AI, Aquaisua AN. Histopathological effect of Nauclea latifolia ethanolic leaf extract and artemether/lumefantrine on the hippocampus of P berghei-infected mice. Int J Brain Cognitive Sci. 2017;6:9–16.

    Google Scholar 

  178. Nworu CS, Ejikeme TI, Ezike AC, Ndu O, Akunne TC, Onyeto CA, et al. Anti-plasmodial and anti-inflammatory activities of cyclotide-rich extract and fraction of Oldenlandia affinis (R.& S.) D.C. (Rubiaceae). Afri Health Sci. 2017;17:827–43.

    Article  Google Scholar 

  179. Ramanitrahasimbola D, Rasoanaivo P, Ratsimamanga-Urverg S, Federici E, Palazzino G, Galeffi C, et al. Biological activities of the plant-derived bisindole voacamine with reference to malaria. Phytother Res. 2001;15:30–3.

    Article  CAS  PubMed  Google Scholar 

  180. Ajala TO1, Igwilo CI, Oreagba IA, Odeku OA. The antiplasmodial effect of the extracts and formulated capsules of Phyllanthus amarus on Plasmodium yoelii infection in mice. Asian Pac J Trop Med. 2011;4:283–7.

  181. Ifeoma O, Samuel O, Itohan AM, Adeola SO. Isolation, fractionation and evaluation of the antiplasmodial properties of Phyllanthus niruri resident in its chloroform fraction. Asian Pac J Trop Med. 2013;6:169–75.

    Article  PubMed  Google Scholar 

  182. Adinew GM. Antimalarial activity of methanolic extract of Phytolacca dodecandra leaves against Plasmodium berghei infected Swiss albino mice. Int J Pharmacol Clin Sci. 2014;3:39–45.

    Google Scholar 

  183. Okokon JE, Antia BS, Igboasoiyi AC, Essien EE, Mbagwu HO. Evaluation of antiplasmodial activity of ethanolic seed extract of Picralima nitida. J Ethnopharmacol. 2007;111:464–7.

    Article  PubMed  Google Scholar 

  184. Madara AA, Ajayi JA, Salawu OA, Tijani AY. Antimalarial activity of ethanolic leaf extract of Piliostigma thonningii Schum (Caesalpiniacea) in mice infected with Plasmodium berghei berghei. Afr J Biotechnol. 2010;9:3475–80.

    Google Scholar 

  185. Christian AG, Ahunna AG, Nwakaego EM, Chimsorom CK, Chile AE. Antimalarial potential of the ethanolic leaf extract of Pseudocedrala kotschyi. J Acute Dis. 2015;4:23–7.

    Article  Google Scholar 

  186. Okokon JE, Ettebong E, Antia BS. In vivo antimalarial activity of ethanolic leaf extract of Stachytarpheta cayennensis. Indian J Pharmacol. 2008;40:111–3.

    Article  PubMed  PubMed Central  Google Scholar 

  187. Adegbolagun OM, Emikpe BO, Woranola IO, Ogunremi Y. Synergistic effect of aqueous extract of Telfaria occidentalis on the biological activities of artesunate in Plasmodium berghei infected mice. Afr Health Sci. 2013;13:970–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  188. Muregi FW, Ishih A, Miyase T, Suzuki T, Kino H, Amano T, et al. Antimalarial activity of methanolic extracts from plants used in Kenyan ethnomedicine and their interactions with chloroquine (CQ) against a CQ-tolerant rodent parasite, in mice. J Ethnopharmacol. 2007;111:190–5.

    Article  PubMed  Google Scholar 

  189. Olanlokun JO, Oluwole MD, Afolayan AJ. In vitro antiplasmodial activity and prophylactic potentials of extract and fractions of Trema orientalis (Linn.) stem barks. BMC Complement Altern Med. 2017;17:407.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  190. Fadare DA, Abiodun OO, Ajaiyeoba EO. In vivo antimalarial activity of Trichilia megalantha harms extracts and fractions in animal models. Parasitol Res. 2013;112:2991–5.

    Article  PubMed  Google Scholar 

  191. François G, Steenackers T, Timperman G, Aké Assi L, Haller RD, Bär S, et al. Retarded development of exoerythrocytic stages of the rodent malaria parasite Plasmodium berghei in human hepatoma cells by extracts from dioncophyllaceae and ancistrocladaceae species. Int J Parasitol. 1997;27:29–32.

    Article  PubMed  Google Scholar 

  192. Akuodor GC, Idris-Usman M, Anyalewechi N, Odo E, Ugwu CT, Akpan JL, et al. In vivo antimalarial activity of ethanolic leaf extract of Verbena hastata against Plasmodium berghei in mice. J Herb Med Toxicol. 2010;4:17–23.

    CAS  Google Scholar 

  193. Njan AA, Adzu B, Agaba AG, Byarugaba D, Díaz-Llera S, Bangsberg DR. The analgesic and antiplasmodial activities and toxicology of Vernonia amygdalina. J Med Food. 2008;11:574–81.

    Article  CAS  PubMed  Google Scholar 

  194. Iwalokun BA. Enhanced antimalarial effects of chloroquine by aqueous Vernonia amygdalina leaf extract in mice infected with chloroquine resistant and sensitive Plasmodium berghei strains. Afr Health Sci. 2008;8:25–35.

    CAS  PubMed  PubMed Central  Google Scholar 

  195. Abosi AO, Raseroka BH. In vivo antimalarial activity of Vernonia amygdalina. Br J Biomed Sci. 2003;60:89–91.

    Article  PubMed  Google Scholar 

  196. Dame ZT, Petros B, Mekonnen Y. Evaluation of anti-Plasmodium berghei activity of crude and column fractions of extracts from Withania somnifera. Turk J Biol. 2013;37:147–50.

    Google Scholar 

  197. Adugna M, Feyera T, Taddese W, Admasu P. In vivo antimalarial activity of crude extract of aerial part of Artemisia abyssinica against Plasmodium berghei in mice. Glob J Pharmacol. 2014;8:460–8.

    Google Scholar 

  198. Deressa T, Mekonnen Y, Animut A. In vivo antimalarial activities of Clerodendrum myricoides, Dodonea angustifolia, and Aloe debrana against Plasmodium berghei. Ethiop J Health Dev. 2010;24:25–9.

    Article  Google Scholar 

  199. Muthaura CN, Rukunga GM, Chhabra SC, Omar SA, Guantai AN, Gathirwa JW, et al. Antimalarial activity of some plants traditionally used in treatment of malaria in Kwale district of Kenya. J Ethnopharmacol. 2007;112:545–51.

    Article  CAS  PubMed  Google Scholar 

  200. Beha E, Jung A, Wiesner J, Rimpler H, Lanzer M, Heinrich M. Antimalarial activity of extracts of Abutilon grandiflorum G Don - a traditional Tanzanian medicinal plant. Phytother Res. 2004;18:236–40.

    Article  CAS  PubMed  Google Scholar 

  201. Ajaiyeoba EO, Abiodun OO, Falade MO, Ogbole NO, Ashidi JS, Happi CT, et al. In vitro cytotoxicity studies of 20 plants used in Nigerian antimalarial ethnomedicine. Phytomedicine. 2006;13:295–8.

    Article  CAS  PubMed  Google Scholar 

  202. Adebayo JO, Balogun EA, Malomo SO, Soladoye AO, Olatunji LA, Kolawole OM, et al. Antimalarial activity of Cocos nucifera Husk fibre: further studes. Evid Based Complement Altern Med. 2013;2013:742476.

    Article  CAS  Google Scholar 

  203. Falade MO, Akinboye DO, Gbotosho GO, Ajaiyeoba EO, Happi TC, Abiodun OO, et al. In vitro and in vivo antimalarial activity of Ficus thonningii Blume (Moraceae) and Lophira alata Banks (Ochnaceae), identified from the ethnomedicine of the Nigerian middle belt. J Parasit Res. 2014;2014:972853.

    Article  CAS  Google Scholar 

  204. Iwalewa EO, Omisore NO, Adewunmi CO, Gbolade AA, Ademowo OG, Nneji C, et al. Anti-protozoan activities of Harungana madagascariensis stem barks extract on trichomonads and malaria. J Ethnopharmacol. 2008;117:507–11.

    Article  CAS  PubMed  Google Scholar 

  205. Gathirwa JW, Rukunga GM, Njagi EN, Omar SA, Mwitari PG, Guantai AN, et al. The in vitro anti-plasmodial and in vivo antimalarial efficacy of combinations of some medicinal plants used traditionally for treatment of malaria by the Meru community in Kenya. J Ethnopharmacol. 2008;115:223–31.

    Article  CAS  PubMed  Google Scholar 

  206. Simelane MBC, Shonhai A, Shode FO, Smith P, Singh M, Opoku AR. Anti-plasmodial activity of some Zulu medicinal plants and of some triterpenes isolated from them. Molecules. 2013;18:12313.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  207. Steele JC, Warhurst DC, Kirby GC, Simmonds MSJ. In vitro and in vivo evaluation of betulinic acid as an antimalarial. Phytother Res. 1999;13:115–9.

    Article  CAS  PubMed  Google Scholar 

  208. Builders MI, Wannang NN, Ajoku GA, Builders PF, Orisadipe A, Aguiyi JC. Evaluation of the antimalarial potential of Vernonia ambigua Kotschy and Peyr (Asteraceae). Int J Pharmacol. 2011;7:238–47.

    Article  Google Scholar 

  209. Ngbolua KN, Rakotoarimanana H, Rafatro H, Ratsimamanga US, Mudogo V, Mpiana PT, et al. Comparative antimalarial and cytotoxic activities of two Vernonia species: Vernonia amygdalina from the Democratic Republic of Congo and Vernonia cinerea subsp vialis endemic to Madagascar. Int J Biol Chem Sci. 2011;5:345–53.

    Google Scholar 

  210. Benoit-Vical F, Imbert C, Bonfils JP, Sauvaire Y. Antiplasmodial and antifungal activities of iridal, a plant triterpenoid. Phytochemistry. 2003;62:747–51.

    Article  CAS  PubMed  Google Scholar 

  211. Applequist WL, Ratsimbason M, Kuhlman A, Ratonandrasana S, Rasamison V, Kingston DG. Antimalarial use of Malagasy plants is poorly correlated with performance in antimalarial bioassays. Econ Bot. 2017;71:75–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  212. Thiengsusuk A, Chaijaroenkul W, NaBangchang K. Antimalarial activities of medicinal plants and herbal formulations used in Thai traditional medicine. Parasitol Res. 2013;112:1475.

    Article  PubMed  Google Scholar 

  213. Udobang JA, Nwafor PA, Okokon JE. Analgesic and antimalarial activities of crude leaf extract and fractions of Acalypha wilkensiana. J Ethnopharmacol. 2010;127:373–8.

    Article  PubMed  Google Scholar 

  214. Mohammed T, Erko B, Giday M. Evaluation of antimalarial activity of leaves of Acokanthera schimperi and Croton macrostachyus against Plasmodium berghei in Swiss albino mice. Compl Altern Med. 2014;14:314.

    Article  Google Scholar 

  215. Kuria KA, De Coster S, Muriuki G, Masengo W, Kibwage I, Hoogmartens J, et al. Antimalarial activity of Ajuga remota Benth (Labiatae) and Caesalpinia Volkensii Harms (Caesalpiniaceae): in vitro confirmation of ethnopharmacological use. J Ethnopharmacol. 2001;74:141–8.

    Article  CAS  PubMed  Google Scholar 

  216. Mesfin A, Giday M, Animut A, Teklehaymanot T. Ethnobotanical study of antimalarial plants in Shineile District, Somali Region, Ethiopia, and in vivo evaluation of selected ones against Plasmodium berghei. J Ethnopharmacol. 2012;139:221–7.

    Article  PubMed  Google Scholar 

  217. Hilou A, Nacoulma OG, Guiguemde TR. In vivo antimalarial activities of extracts from Amaranthus spinosus L. and Boerhaavia erecta L. in mice. J Ethnopharmacol. 2006;103:236–40.

    Article  CAS  PubMed  Google Scholar 

  218. Adebajo AC, Odediran SA, Aliyu FA, Nwafor PA, Nwoko NT, Umana US. In vivo antiplasmodial potentials of the combinations of four Nigerian antimalarial plants. Molecules. 2014;19:13136–46.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  219. Dikasso D, Mekonnen E, Debella A, Abebe D, Urga K, Menonnen W, et al. In vivo antimalarial activity of hydroalcoholic extracts from Asparagus africanus Lam in mice infected with Plasmodium berghei. Ethiop J Health Dev. 2006;20:112–8.

    Google Scholar 

  220. Yerbanga RS, Lucantoni L, Lupidi G, Dori GU, Tepongning NR, Nikiéma JB, et al. Antimalarial plant remedies from Burkina Faso: their potential for prophylactic use. J Ethnopharmacol. 2012;140:255–60.

    Article  PubMed  Google Scholar 

  221. Karou SD, Tchacondo T, Ouattara L, Anani K, Savadogo A, Agbonon A, et al. Antimicrobial, antiplasmodial, haemolytic and antioxidant activities of crude extracts from three selected Togolese medicinal plants. Asian Pac J Trop Med. 2011;4:808–13.

    Article  PubMed  Google Scholar 

  222. Bonkian LN, Yerbanga RS, Koama B, Soma A, Cisse M, Valea I, et al. In vivo antiplasmodial activity of two Sahelian plant extracts on Plasmodium berghei ANKA infected NMRI mice. Evid Based Complement Alternat Med. 2018;24:6859632.

    Google Scholar 

  223. Ajaiyeoba E, Ashidi J, Abiodun O, Okpako L, Ogbole O, Akinboye D, et al. Antimalarial ethnobotany: in vitro antiplasmodial activity of seven plants indentified in the Nigerian middle belt. Pharm Biol. 2005;42:588–91.

    Article  Google Scholar 

  224. Kefe A, Giday M, Mamo H, Erko B. Antimalarial properties of crude extracts of seeds of Brucea antidysenterica and leaves of Ocimum lamiifolium. BMC Complement Altern Med. 2016;16:118.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  225. Innocent E, Moshi MJ, Masimba PJ, Mbwambo ZH, Kapingu MC, Kamuhabwa A. Screening of traditionally used plants for in vivo antimalarial activity in mice. Afr J Tradit Complement Altern Med. 2009;6:163–7.

    PubMed  PubMed Central  Google Scholar 

  226. Mengiste B, Mekonnen E, Urga K. In vivo animalarial activity of Dodonaea angustifolia seed extracts against Plasmodium berghei in mice model. MEJS. 2012;4:147–63.

    Article  Google Scholar 

  227. Biruksew A, Zeynudin A, Alemu Y, Golassa L, Yohannes M, Debella A, et al. Zingiber officinale Roscoe and Echinops kebericho Mesfin showed antiplasmodial activities against Plasmodium berghei in a dose-dependent manner in Ethiopia. Ethiop J Health Sci. 2018;28:655.

    PubMed  PubMed Central  Google Scholar 

  228. Agbaje EO, Onabanjo AO. The effects of extracts of Enantia chlorantha in malaria. Ann Trop Med Parasitol. 1991;85:585–90.

    Article  CAS  PubMed  Google Scholar 

  229. Ajayi EIO, Adelekeb MA, Adewumia TY, Adeyemia AA. Antiplasmodial activities of ethanol extracts of Euphorbia hirta whole plant and Vernonia amygdalina leaves in Plasmodium berghei-infected mice. J Taibah Univ Sci. 2017;11:831–5.

    Article  Google Scholar 

  230. Omole AR, Malebo MH, Nondo SOR, Katani S, Mbugi H, Midiwo J, et al. In vivo anti-plasmodial activity of crude extracts of three medicinal plants used traditionally for malaria treatment in Kenya. Eur J Med Plants. 2018;24:1–7.

    Article  Google Scholar 

  231. Nureye D, Assefa S, Nedi T, Engidawork E. In vivo antimalarial activity of the 80% methanolic root barks extract and solvent fractions of Gardenia ternifolia Schumach & Thonn (Rubiaceae) against Plasmodium berghei. Evid Based Complement Alternat Med. 2018;2018:9217835.

    Article  PubMed  PubMed Central  Google Scholar 

  232. Beaufay C, Hérent MF, Quetin-Leclercq J, Bero J. In vivo antimalarial activity and toxicity studies of triterpenic esters isolated from Keetia leucantha and crude extracts. Malar J. 2017;16:406.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  233. Bankole AE, Adekunle AA, Sowemimo AA, Umebese CE, Abiodun O, Gbotosho GO. Phytochemical screening and in vivo antimalarial activity of extracts from three medicinal plants used in malaria treatment in Nigeria. Parasitol Res. 2016;115:299–305.

    Article  CAS  PubMed  Google Scholar 

  234. Jansen O, Tchinda AT, Loua J, Esters V, Cieckiewicz E, Ledoux A. Antiplasmodial activity of Mezoneuron benthamianum leaves and identification of its active constituents. J Ethnopharmacol. 2017;203:20–6.

    Article  CAS  PubMed  Google Scholar 

  235. Udobre AS, Udobang JA, Udoh AE, Anah VU, Akpan AE, Charles GE. Effect of methanol leaf extract of Nauclea latifolia on albino mice infected with Plasmodium berghei berghei. Afr J Pharmacol Ther. 2013;2:83–7.

    Google Scholar 

  236. Mesia K, Tona L, Mampunza MM, Ntamabyaliro N, Muanda T, Muyembe T, et al. Antimalarial efficacy of a quantified extract of Nauclea pobeguinii stem barks in human adult volunteers with diagnosed uncomplicated falciparum malaria .Part 2: a clinical phase IIB trial. Planta Med. 2012;78:853–60.

    Article  CAS  PubMed  Google Scholar 

  237. Okeola VO, Adaramoye OA, Nneji CM, Falade CO, Farombi EO, Ademowo OG. Antimalarial and antioxidant activities of methanolic extract of Nigella sativa seeds (black cumin) in mice infected with Plasmodium yoelii nigeriensis. Parasitol Res. 2011;108:1507–12.

    Article  PubMed  Google Scholar 

  238. Girma S, Giday M, Erko B, Mamo H. Effect of crude leaf extract of Osyris quadripartita on Plasmodium berghei in Swiss albino mice. BMC Complement Alternative Med. 2015;15:184.

    Article  Google Scholar 

  239. Kabiru AY, Ibikunle GF, Innalegwu DA, Bola BM, Madaki FM. In vivo antiplasmodial and analgesic effect of crude ethanol extract of Piper guineense leaf extract in Albino Mice. Scientifica (Cairo). 2016: 8687313.

  240. Hiben MG, Sibhat GG, Fanta BS, Gebrezgi HD, Tesema SB. Evaluation of Senna singueana leaf extract as an alternative or adjuvant therapy for malaria. J Tradit Complement Med. 2015;6:112–7.

    Article  PubMed  PubMed Central  Google Scholar 

  241. Tadesse SA, Wubneh ZB. Antimalarial activity of Syzygium guineense during early and established Plasmodium infection in rodent models. BMC Complement Alternative Med. 2017;17:21.

    Article  CAS  Google Scholar 

  242. Adepiti AO, Iwalewa EO. Evaluation of the combination of Uvaria chamae (P Beauv) and amodiaquine in murine malaria. J Ethnopharmacol. 2016;193:30–5.

    Article  CAS  PubMed  Google Scholar 

  243. Masaba SC. The antimalarial activity of Vernonia amygdalina Del (Compositae). Trans R Soc Trop Med Hyg. 2000;94:694–5.

    Article  CAS  PubMed  Google Scholar 

  244. Omoregie ES, Pal A. Antiplasmodial, antioxidant and immunomodulatory activities of ethanol extract of Vernonia amygdalina del. leaves in Swiss mice. Avicenna J Phytomed. 2016;6:236–7.

    CAS  PubMed  PubMed Central  Google Scholar 

  245. Challand S, Willcox M. A Clinical trial of the traditional medicine Vernonia amygdalina in the treatment of uncomplicated Malaria. J Altern Complement Med. 2009;15:1231–7.

    Article  PubMed  Google Scholar 

  246. Ajayi BB, Ogunsola JO, Olatoye OI, Antia RE, Agbedea S. Effects of pituitary extract, ovaprim, and bitter leaves (Vernonia amygdalina) on the histopathology of African catfish (Clarias gariepinus) Aquacult. Fish. 2018;3:232–7.

    Google Scholar 

Download references

Acknowledgements

I would like to express my special appreciation and thanks to Professor Dr. Wanderley de Souza for his helpful comments.

Funding

N/A.

Author information

Authors and Affiliations

  1. Department of Microbiology, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran

    Elahe Tajbakhsh

  2. Department of Biomedical Science, Faculty of Health Sciences, Regional Hospital Buea, Buea, Cameroon

    Tebit Emmanuel Kwenti

  3. Department of Public Health and Hygiene, Faculty of Health Sciences, University of Buea, Yaoundé, Cameroon

    Tebit Emmanuel Kwenti

  4. Department of Medical Laboratory Sciences, Faculty of Health Sciences, University of Buea, Yaoundé, Cameroon

    Tebit Emmanuel Kwenti

  5. Young Researchers and Elite Club, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran

    Parya Kheyri & Saeed Nezaratizade

  6. Department of Biomedical Sciences and Pathobiology, Center for One Health Research, Virginia Maryland College of Veterinary Medicine, Virginia Tech, 1410 Prices Fork Road, Blacksburg, VA, 24061-0342, USA

    David S. Lindsay

  7. Shahrekord Branch, Islamic Azad University, Shahrekord, Iran

    Faham Khamesipour

  8. Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Faham Khamesipour

Authors
  1. Elahe Tajbakhsh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tebit Emmanuel Kwenti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Parya Kheyri
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Saeed Nezaratizade
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. David S. Lindsay
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Faham Khamesipour
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed equally to the study. All authors read and approved the manuscript.

Corresponding author

Correspondence to Faham Khamesipour.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1: Table S1.

In vitro and in vivo studies reporting inactive antiplasmodial or antimalarial activity. Table S2. List of active compounds identified from plants.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tajbakhsh, E., Kwenti, T.E., Kheyri, P. et al. Antiplasmodial, antimalarial activities and toxicity of African medicinal plants: a systematic review of literature. Malar J 20, 349 (2021). https://doi.org/10.1186/s12936-021-03866-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12936-021-03866-0

Keywords

Malaria Journal

ISSN: 1475-2875

Contact us