Evidence-Based Complementary and Alternative Medicine

Evidence-Based Complementary and Alternative Medicine / 2019 / Article
Special Issue

Natural Products as Sources of Antimalarial Drugs

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Review Article | Open Access

Volume 2019 |Article ID 3057180 | 27 pages | https://doi.org/10.1155/2019/3057180

Exploring Antimalarial Herbal Plants across Communities in Uganda Based on Electronic Data

Academic Editor: Vivitri D. Prasasty
Received05 Jun 2019
Accepted14 Aug 2019
Published15 Sep 2019

Abstract

Malaria is one of the most rampant diseases today not only in Uganda but also throughout Africa. Hence, it needs very close attention as it can be severe, causing many deaths, especially due to the rising prevalence of pathogenic resistance to current antimalarial drugs. The majority of the Ugandan population relies on traditional herbal medicines for various health issues. Thus, herein, we review various plant resources used to treat malaria across communities in Uganda so as to provide comprehensive and valuable ethnobotanical data about these plants. Approximately 182 plant species from 63 different plant families are used for malaria treatment across several communities in Uganda, of which 112 plant species have been investigated for antimalarial activities and 96% of the plant species showing positive results. Some plants showed very strong antimalarial activities and could be investigated further for the identification and validation of potentially therapeutic antimalarial compounds. There is no record of an investigation of antimalarial activity for approximately 39% of the plant species used for malaria treatment, yet these plants could be potential sources for potent antimalarial remedies. Thus, the review provides guidance for areas of further research on potential plant resources that could be sources of compounds with therapeutic properties for the treatment of malaria. Some of the plants were investigated for antimalarial activities, and their efficacy, toxicity, and safety aspects still need to be studied.

1. Introduction

Malaria, a dangerous and life-threatening disease caused by Plasmodium parasites is spread to humans through bites of infected female Anopheles mosquitoes [1]. It is one of the most widespread diseases today not only in Uganda but also throughout Africa. Hence, careful monitoring of malaria is required as the disease can be severe and can cause many deaths, especially due to the increasing prevalence of resistance to current antimalarial drugs. Among the five parasitic species that cause malaria to humans, Plasmodium falciparum and Plasmodium vivax are the deadliest [2, 3]. P. falciparum and P. vivax being the most prevalent malaria parasites in sub-Saharan Africa and regions of the Americas, respectively, were responsible for about 99.7% and 74.1% of malaria cases in 2017 [4]. In Southeast Asia, Plasmodium knowlesi is the most common cause of malaria, accounting for up to 70% of malaria cases, although it has been known to infect Old-World monkeys more [5]. Two other species of Plasmodium, Plasmodium malariae and Plasmodium ovale, generally cause mild fevers. Approximately 216 million malaria cases were registered in 2016, with a death toll of up to 445,000 [1]. According to the World Health Organization [6], the incidence of malaria in Uganda, at 47.8%, was the highest worldwide in 2005. According to Njoroge and Bussman [7], malaria is responsible for one to two million deaths annually in Africa. Typical symptoms of malaria include high fever, fatigue, headache, muscle ache, nausea, abdominal discomfort, and profuse sweating. However, in extreme cases and cases of prolonged illness without treatment, brain tissue injury, pulmonary edema, kidney failure, severe anemia, yellow discoloration of the skin, and low blood sugar may be noted (Figure 1) [1, 2]. In Uganda, malaria is one of the major causes of illness and death [7]. Statistically, it accounts for 46% of children’s sicknesses, almost 40% of outpatient visits to hospitals and clinics, 25% of hospital admissions, 14% of inpatient deaths, and approximately 23% of infant mortalities [7].

In different parts of the world, the use of herbs and herbal extracts in the management and treatment of malaria is very common since herbs are cheap and readily available besides being effective. In fact, the use of herbal medicine for treatment worldwide is on the rise. Over 80% of the Ugandan population relies directly on herbal plants for their health care primarily [8]. A great majority of the population uses traditional herbal medicines because of their confirmed therapeutic value [8]. The increase in preference for herbal remedies coupled with resistance exhibited by pathogenic strains, including Plasmodium species, to the modern drugs available is the driving force behind researchers’ interest in herbal plants for possible alternatives for more effective antimalarial drugs [9, 10].

This review was aimed at providing comprehensive ethnobotanical information about various plant resources with antimalarial properties that are primarily used to manage and treat malaria across communities in Uganda, based on which further evaluation of these plants such as those of their efficacy and safety for the treatment of malaria may be based.

2. Methods and Materials

In the review, the data search processes employed by Komakech et al. [11] were modified to gather information on herbal plants for malaria treatment in Uganda from peer-reviewed articles in English published in scientific journals and other verifiable databases, with a focus on plant species and families, plant parts used, antimalarial activities of the extracts from herbal plants, and mechanisms of action of novel antimalarial phytochemicals and derivatives. Electronic literature databases such as PubMed, Medline, Scopus, SciFinder, Google Scholar, and Science Direct were carefully searched for suitable information. The following words were used as key search terms: (“Herbal medicine in Uganda” OR “Herbs in Uganda” OR “Traditional remedies in Uganda” OR “Natural remedies in Uganda” OR “Anti-malarial herbs in Uganda” OR “Anti-malarial plants in Uganda” OR “Ugandan herbs” OR “Ugandan ethno-medicine” OR “Ugandan phyto-medicine”), AND (“anti-plasmodial activities” OR “anti-malarial activities” OR “anti-plasmodial effects” OR “anti-malarial effects” OR “malaria treatment” OR “malaria management”) OR (“Malaria in Uganda” AND “prevalence” OR “occurrence” OR “distribution” OR “herbal treatment” OR “herbal remedies” OR “phyto-medicine” OR “phyto remedy” OR “plant parts used for treatment”) OR (Phytochemicals for malaria treatment OR Artemisinins OR Quinine OR Noble anti-malarial compounds OR Plant derived anti-malarial compounds AND mechanisms of action OR modes of action) OR (“Malaria herbal medicine in Uganda” OR “Herbal medicine in Uganda” OR “Herbal malaria remedy in Uganda” OR “Natural malaria medicine in Uganda” OR “Traditional malaria herbal medicine” OR “Malaria herbal recipe” AND “dosage” OR “dose” OR “dose given” OR “mode of administration” OR “means of traditional extraction” OR “traditional extraction” OR “Toxicity” OR “Safety and toxicity” OR “Policy framework” OR “other ethno-pharmacological uses” OR “other ethno-pharmacological utilizations” OR “other ethno-medicinal uses”). The information gathered was verified separately for its reliability; any discrepancies discovered were resolved by discussions between the authors. Thereafter, these data were summarized and analyzed, and comparisons were made to draw conclusions.

3. Prevalence of Malaria

Malaria in Uganda is highly endemic because the climate is favorable for its consistently stable and year-round transmission in about 99% of the country, with the country’s entire population being at risk for contraction [12]. The most vulnerable groups of people at great risk for malaria are expectant mothers and young children under the age of 5 years [12]. The malarial parasite, P. falciparum, is most commonly the cause of malaria throughout Uganda, accounting for over 90% of malaria cases. However, Betson et al. [13] have warned of the potential for the emergence of infections due to P. malariae and P. ovale spp. as well, since there is much focus on countering P. falciparum infections. In 2016, Larocca et al. [14] indicated that Uganda was one of the leading countries in the world with malaria incidence rate as high as 478 cases per 1,000 population per year. Specifically, overall registered death cases caused by malaria in children were between 70,000 and 100,000 annually in Uganda [14]. Tremendous effort has been made to control malaria in Uganda by the government-headed Uganda Malaria Reduction Strategic Plan and Mass Action Against Malaria. These efforts have greatly reduced the malaria burden and incidence from 272 cases per 1000 population in 2016/17 to 191 cases per 1000 population in 2017/18 [12]. Although there has been a general reduction in the incidence of malaria, studies indicate that malaria prevalence along lakes, for example, Lake Victoria, and in remote areas of the country (villages) as well as areas closer to forests are much higher, with over 450 malaria cases per 1000 population (Figure 2) [12, 13, 15]. Communities around lakeshores in Uganda have always had high prevalence of malaria among children and especially the young ones despite routine treatments [12, 16]. Through the government initiative to control malaria, the prevalence in some districts remained as low as 4.3% in 2018 [12]. Malaria control strategies including indoor residual spraying along with house to house distribution of mosquito nets treated with insecticides resulted in a remarkable reduction in malaria burdens in many parts of the country [17]. Raouf et al. [18] observed that significant reductions in the levels of malaria in Uganda cannot be sustained if the current control measures are terminated.

4. Mechanisms of Actions of Novel Phytochemicals in Malaria Treatment

Herbal plants are extremely rich in phytochemicals that are highly efficacious in the treatment of malaria, such as sesquiterpenes and sesquiterpene lactones, fluoroquinolones, chalcones, flavanones, phenolics, quinones, coumarins, and alkaloids (Table 1) [35, 36]. The herbal plants that are used as prophylactic measures to prevent malaria as well contain some of these compounds (Table 2). From these groups of compounds, active metabolites including quinine and artemisinin have been derived and the most successful antimalarial drugs to date have been obtained. Artemisinins from Artemisia annua a plant belonging to the family Asteraceae have actually been an integral part of the fight against malaria, with artemisinin-based combination therapy contributing enormously to modern day treatments [36]. They have been effective against all strains of P. falciparum including multi-drug-resistant ones [36, 37].


Plant familyScientific nameLocal namePart usedGrowth formMode of preparationDose and mode of administration for malariaStatus of antimalarial/antiplasmodial activity investigationOther ailments treatedReference(s)

AcanthaceaeJusticia betonica L.Nalongo/quinineLeaves/whole plantHerbDecoctionAbout 120 ml every 8 hours for a weekInvestigatedDiabetes, yellow fever, diarrhea[10, 19]
Justicia anselliana (Nees) T. AndersonKwiniini omugandaLeaves/twigHerbDecoctionOrally taken, dose not specifiedNo record[20]
Monechma subsessile C. B. ClarkeEraziLeavesDecoctionOrally taken, dose not specifiedNo recordAbdominal pain[19]
Thunbergia alata SimsKasaamusaamu/ntudde bulekuLeaves/whole plantClimberDecoctionAbout 120 ml every 8 hours for a weekNo recordFalse teeth[8, 10]
AlliaceaeAllium cepa L.KatunguluBulbHerbNo record[21]
AloeaceaeAloe dawei A. Berger (wild/cultivated)KigagiLeavesHerbDecoctionA glassful once a day for 7 daysInvestigatedCandida[10]
Aloe kedongensis (wild)KigagiLeavesHerbDecoctionOrally taken, dose not specifiedInvestigated[19, 22]
Aloe volkensii (cultivated)KigagiLeavesHerbDecoction/infusionOrally taken, dose not specifiedNo record[19]
Aloe ferox MillKigagiLeavesHerbDecoctionOrally taken, dose not specifiedInvestigatedWounds, digestive disorders, rheumatic arthritis[18, 19]
Aloe lateritia (wild)KigagiLeaves/rootHerbDecoctionOrally taken, dose not specifiedNo record[19]
AmaranthaceaeAmaranthus hybridus L.BbugaLeavesHerbDecoctionHalf a glass every 24 hours for 7 daysNo record[10]
AnacardiaceaeMangifera indica L.Muyembe gwakonaLeaves/barkTreeDecoction4 and 3 teaspoons after every 8 hours for adults and children, respectively, for a weekInvestigatedDiarrhea, dysentery, body pain, venereal diseases, cough, syphilis[10, 23]
Rhus natalensis Bernh. Ex KraussOmeshesheLeavesShrubDecoctionOrally taken, dose not specifiedInvestigated[24]
Rhus vulgaris MeikleKakwasokwaso/tebuddaLeavesShrubDecoctionHalf a glass every 8 hours for 7 daysNo recordSkin rush, erectile dysfunction[10]
ApiaceaeHeteromorpha trifoliata Eckl. & Zeyh.OmumemenaLeaves/rootsHerbDecoctionOrally taken, dose not specifiedNo record[19]
Centella asiatica (L.) Urb.Kabo Kabakyala/mbutamuLeaves/whole plantHerbDecoction4 teaspoons thrice a day for 4 daysInvestigated[10]
ApocynaceaeAlstonia boonei De Wild.MubajangalabiBarkTreeDecoctionOrally taken, dose not specifiedInvestigated[8]
Carissa edulis (Forssk.) VahlMuyunza, ekamurieiRootsHerbDecoctionOrally taken, dose not specifiedInvestigatedEpilepsy, fever, cough, syphilis, measles, dysentery[21, 23]
Carissa spinarum Lodd. ex A. DC.OmuyonzaRootsDecoctionOrally taken, dose not specifiedInvestigated[19]
Catharanthus roseus G. DonSekagyaLeavesHerbDecoctionAbout 120 ml every 8 hours for a weekInvestigated[10]
AraceaeCulcasia faleifolia Engl.Ntangawuzi yomukibiraRootsHerbDecoctionAbout 120 ml once a day for a weekNo record[10]
AristolochiaceaeAristolochia elegans Mast.Musuja welaba/nakaseroSeeds/sapVineSteeped in water and drunkA glassful once a dayInvestigatedAbdominal pain, East coast fever[8, 19]
Aristolochia tomentosa Sims.KankapuStemClimberInfusionOral, dose not specifiedNo recordWounds, skin diseases, snake bites[23]
AsclepiadaceaeGomphocarpus physocarpus E. Mey.KafumboLeavesHerbDecoctionHalf a glass daily for a weekNo record[10]
AsphodelaceaeAloe vera (L.) Burm. f.Kigagi/aloveraLeavesHerbDecoction1 teaspoon and 1 tablespoon 3 times a day for children and adults, respectively, for a weekInvestigatedStomach ache[8, 25]
AsteraceaeAgeratum conyzoides L.NamirembeWhole plant/leavesHerbDecoctionA glassful thrice a day for 7 daysInvestigatedWorms, weakness in pregnancy[8, 10]
Artemisia annua L.Sweet anneLeavesHerbDecoctionOral, dose not specifiedInvestigatedFever[19]
Artemisia afra Jacq. ex WilldPasileLeavesHerbInfusionOral, dose not specifiedInvestigatedFever[10]
Aspilia africana (Pers.) C. D. AdamsMakayi, ekarweWhole plant/leaves/rootsHerbDecoction8 teaspoons 3 times a day for a weekInvestigatedAbdominal aches, measles, diarrhea, wounds, induction of appetite[10, 19]
Baccharoides adoensis (Sch. Bip. ex Walp.) H. Rob.OkellokelloLeavesShrubDecoction1 teaspoon and 1 tablespoon 3 times a day for children and adults, respectively, for a week; bath-leaves squeezed and added to bathing waterInvestigatedFlu, skin rush, ear infections[25, 26]
Bidens grantii SherffEhongwaLeaves, flowerHerbDecoctionOral, dose not specifiedNo recordPregnancy disorders, prehepatic jaundice[19]
Bidens pilosa L.Sere/labikaWhole plant/leavesHerbDecoction/fresh leaf extract4 teaspoons thrice a day for 4 daysInvestigatedDiarrhea, wounds[10, 23]
Bothriocline longipes N. E. Br.EkyogayanjaLeavesDecoctionOral, dose not specifiedInvestigatedFever, ague, paludism[19, 24]
Conyza bonariensis (L.)NdashaLeavesDecoctionOral, dose not specifiedNo recordStomach ache, body pain, anemia, respiratory problems[19]
Conyza floribunda H. B. K.KafumbeLeavesHerbDecoctionAbout 120 ml once a day for a weekNo recordHeadache[10]
Conyza sumatrensis (Retz.) E. H. WalkerKati katiLeavesHerbNo recordWounds, sore throat, ringworms[21, 27]
Crassocephalum vitellinumKitontoLeavesHerbHoney added to decoction2 teaspoons thrice a day for 7 daysInvestigated[10, 19]
Emilia javanica (Burm. F.) C. B. Rob.NakateWhole plantHerbDecoctionHalf a glass once a day for a weekNo record[10]
Guizotia scabra Chiov.EkiterankubaLeavesDecoctionOral, dose not specifiedInvestigatedStomach ache, HIV/AIDS opportunistic infections[19]
Gynura scandens O. Hoffm.Ekizimya-muriroLeavesDecoctionOral, dose not specifiedNo recordFebrile convulsions[19]
Melanthera scandens (Schumach. & Thonn.) RobertyMakaayiLeavesHerbDecoctionOral, dose not specifiedInvestigatedStomach ache, body odour, yellow fever[8]
Pluchea ovalis DC.OmuneeraLeavesDecoctionOral, dose not specifiedNo record[19]
Microglossa pyrifolia (Lam.)O. KtzeKafugankandeWhole plant/leaves/rootsHerbDecoctionHalf a glass thrice a day for a weekInvestigatedCough, abdominal disorders, chest pain[10, 19, 28]
Schkuhria pinnata (Lam.)ApunaitLeavesHerbInfusion1 teaspoon and 1 tablespoon 3 times a day for children and adults, respectively, for a weekInvestigatedWounds, skin diseases, diabetes, ear infections, wounds[23, 25]
Sigesbeckia orientalis L.KyaryahoRootsDecoctionOral, dose not specifiedNo recordWounds, stomach ache[19]
Solanecio mannii (Hook. f.) C. JeffreyOmusununuLeavesDecoctionOral, dose not specifiedInvestigatedFever, indigestion[19]
Sonchus oleraceus L.EntahutaraLeavesDecoctionOral, dose not specifiedNo recordStomach ache, scars, anemia, diarrhea[8, 19]
Tagetes minuta L.KawunyiraWhole plant/leavesHerbDecoctionHalf a glass thrice a day for a weekInvestigatedFlu, headache, convulsions[10]
Tithonia diversifolia A. GrayKimyulaLeavesHerbDecoctionHalf a glass thrice a day for a weekInvestigatedDiabetes, abdominal pain[10, 19, 25]
Vernonia adoensis Sch. Bip. ex Walp.NyakajumaLeaves/flowersDecoctionOral, dose not specifiedInvestigatedDiarrhea, dizziness[19]
Vernonia amygdalina DelileMululuza/labworiWhole plant/rootsShrubDecoctionHalf a glass 2 times a day for 5 daysInvestigatedHeadache, stomach ache, burns, baths[8, 10, 19, 20]
Vernonia cinerea (L.) Less.KayayanaBarkTreeDecoctionHalf a glass thrice a day for a weekInvestigatedFever, vomiting, inflammation[10]
Vernonia lasiopus O. Hoffm.Kaluluza kasajjaRoots/leavesShrubFresh leaf extract/root decoction2 teaspoons thrice a day for 7 daysInvestigatedAbdominal pain, cough, migraine headache, delayed delivery[8, 10, 19, 20]
BignoniaceaeMarkhamia lutea (Benth.) K. Schum.Musambya/muzangandaRootsTreeDecoctionA glassful once a day for 7 daysInvestigatedCough, diarrhea[8, 10, 19]
Spathodea campanulata Buch. -Harm. ex DC.KifabakaziBarkTreeDecoctionHalf a glass 3 times a day for 5 daysInvestigatedIncreased vaginal fluid, skin infection, infertility, hernia[8, 10]
CaesalpiniaceaeCassia didymobotrya Fres.MukyulaLeavesShrubDecoctionAbout 120 ml every 8 hours for a weekInvestigated[10]
Chamaecrista nigricans GreeneEpeduru lo didiLeavesHerbInfusionOral, dose not specifiedNo recordLabour induction, hypertension, retained placenta[23]
Erythrophleum pyrifoliaOmuramaLeaves/rootsInvestigated[24]
Senna spectabilis (DC.) H. S. Irwin & BarnebyGasiyaLeavesTreeDecoctionHalf a glass twice a day for 5 daysInvestigated[10]
CaesalpinioideaeCassia hirsutaKasagalansansiRootsHerbInfusionInvestigatedStomach pains[23]
CanelliaceaeWarbugia ugandensis SpragueOmukuzanumeBark/leavesTreeDecoction/powder swallowed with bananaHalf a glass once a day for a weekInvestigatedToothache, flu, skin diseases, asthma, stomach ache, body and muscle pain[10, 20, 27]
CaricaceaeCarica papaya L.Paapali essajjaLeavesTreeDecoctionHalf a glass twice a day for 3 daysInvestigatedSnake bite, sterility, cough, cancer, body pain, induces labour[10, 19, 23, 25]
CelastraceaeMaytenus senegalensisEchomaiRootsTreeDecoctionOral, dose not specifiedInvestigatedToothache, skin diseases, chest pain, wound, fever[23]
ChenopodiaceaeChenopodium ambrosioides L.Kawuna wunaLeavesInvestigatedHeadache, epilepsy[21]
Chenopodium opulifolium Koch & ZizNamuvuLeavesNo recordOral wounds, skin rush, toothache[8, 21]
CombretaceaeCombretum molle G. DonNdagiBarkTreeDecoctionHalf a glass once a day for 3 daysInvestigatedCough,[10, 21]
CrassulaceaeKalanchoë densiflora RolfeKisanasanaLeavesHerbNo record[21]
CucurbitaceaeCucurbita maxima Lam.KasuunsaLeavesHerbDecoctionHalf a glass once a day for 7 daysInvestigatedAbdominal pain[10, 25, 27]
Momordica foetida Schumach.OrwihuraLeavesDecoctionOral, dose not specifiedInvestigatedVomiting, baths, cough, flue, worms[19, 26, 28]
DracaenaceaeDracaena steudneri Engl.KajjolyenjovuLeavesHerbDecoctionHalf a glass thrice a day for a weekNo recordScars, cough, syphilis, kidney stones, snake bites[8, 10]
EbenaceaeEuclea latideus StaffEmusiRootsShrubDecoctionOral, dose not specifiedInvestigatedRingworms, swollen legs[23]
EuphorbiaceaeAlchornea cordifolia (Schumach.) Mull. Arg.LuzibazibaLeavesHerbDecoctionHalf a glass once a day for 7 daysInvestigatedShaking body[8, 10]
Bridelia micrantha Baill.KatazamitiBarkTreeDecoctionHalf a glass thrice a day for a weekInvestigated[10]
Clutia abyssinica Jaub. & SpachOmubaramaLeavesDecoctionOral, dose not specifiedInvestigatedFever, diarrhea[19]
Croton macrostachyus Olive.OokotaRoots/barkTreeDecoctionOral, dose not specifiedInvestigatedTuberculosis, stomach ache, cough, fever, asthma[23]
Fluegea virosa (Roxb. ExWillb.)VoigtLukandwa/mukandulaLeavesShrubDecoctionHalf a glass 3 times a day for a weekInvestigatedMiscarriage, chest pains, infertility in women[8, 10, 21, 23]
Jatropha curcas L.KirowaLeavesShrubInvestigatedTooth decay, headache, weakness in pregnancy[21]
Macaranga schweinfurthii PaxKyeganzaBarkTreeDecoctionHalf a glass 3 times a day for a 5 daysNo record[10]
Phyllanthus (pseudo) niruri Mull. Arg.NakitembeLeavesShrubDecoctionHalf a glass 3 times a day for a 7 daysInvestigated[10]
Shirakiopsis elliptica (Hochst.) H.–J. EsserMusasaBackTreeDecoctionOral, dose not specifiedNo record[20]
Tetrorchidium didymostemon (Baill.) Pax & K. Hoffm.EkiziranfuBarkDecoctionUsed as enemaNo recordJaundice, measles, gastrointestinal disorders, enema[8, 19]
FabaceaeArachis hypogea (NC)EbinyobwaLeavesFresh extractOral, dose not specifiedNo record[19]
Cajanus cajan (L.) DruseEntondaigwaLeavesShrubFresh extract100 ml once a day for a weekInvestigatedDiarrhea, body pain[27]
Crotalaria agatiflora Schweinf.KijjebejebbeWhole shootShrubFresh extractDaily bathNo recordHigh blood pressure[10]
Crotalaria ochroleuca G. DonAlayoLeavesHerbFresh extract1 teaspoon and 1 tablespoon 3 times a day for children and adults, respectively, for a weekNo recordStomach ache[28]
Entada abyssinica Steud. ex A. Rich.MwololaLeavesTreeDecoctionInvestigatedOral wounds, body weakness, wounds, skin infections[8, 20, 26]
Entada africana Guill. & Perr.MwololaBarkTreeDecoction4 and 3 teaspoons after every 8 hours for adults and children, respectively, for a weekInvestigated[10]
Erythrina abyssinica Lam.Girikiti/lacoroBarkTreeDecoctionHalf a glass 3 times a day for a 5 daysInvestigatedFever, leprosy, burns, tuberculosis, toothache, syphilis[10, 23]
Erythrina excelsa Bak.BajjangalaBarkTreeDecoctionHalf a glass 3 times a day for a weekNo recordWounds, candida[10]
Indigofera arrecta Hochst. Ex A. RichOmushorozaRoots/barkNo recordAbdominal pain[19]
Indigofera congesta BakerNamasumiTwigHerbInfusionOral, dose not specifiedNo record[8, 20]
Indigofera emerginella Steud. ex A. RichOmunyazabashumbaLeaves/rootsShrubDecoctionOral, dose not specifiedInvestigatedCough[19]
Macrotyloma axillare Verdc.AkihabukuruLeavesNo recordImpotence, dizziness[19]
Pseudarthria hookeri Wight & ArnOmukongorani/kikakalaLeaves/whole plantHerbDecoctionOne teaspoon thrice a day for 4 daysNo recordFever[19, 20, 25, 29]
Rhynchosia viscosa DCOmutegansiFlowerNo recordLabour induction[19]
Senna absus (L.) Roxb.MucuulaShrubLeavesFresh extractOral, dose not specifiedNo recordProlonged embryo in uterus[8]
Senna didymobotrya (Fresen.) H. S. Irwin & BarnebyOmugabagaba/kivumuziHerbLeaves, twigDecoctionOral, dose not specifiedInvestigatedChange of sex of child[8, 19, 20, 29]
Senna siamea (Lam.) H. S. Irwin & BarnebyGarciaRootsTreeFresh extractA cupful (500 ml) once a day for 3 daysInvestigatedAbdominal pain, sore throat[25, 27]
Tamarindus indica L.Cwaa/nkogeBarkTreeDecoctionOral, dose not specifiedInvestigatedConvulsions, fever[8, 21]
FlacourtiaceaeOcoba spinosa ForsskEkalepulepuRootsHerbDecoctionOral, dose not specifiedNo recordSyphilis, skin problems, wounds, headache, impotence, stomach ache[23]
Trimeria bakeri Gilg.OmwatanshareLeavesShrubDecoctionOral, dose not specifiedInvestigated[24]
HypericaceaeHarungana madagascariensis Lam.Mukaabiransiko/muliriraBarkTreeDecoction2 tablespoons thrice a day for 3 daysInvestigatedYellow fever[8, 10]
LabiataeHyptis pectinata Poir.BongolozaWhole plantHerbDecoctionOral, dose not specifiedNo record[20, 29]
LamiaceaeAeolanthus repens Oliv.NtulagiLeavesHerbDecoctionQuarter a glass thrice a day for 3 daysNo record[10]
Ajuga remota Benth.KitinwaLeavesHerbDecoctionHalf a glass once a day for a weekInvestigatedStomach ache[10]
Clerodendrum myricoides R. Br.KikongeLeavesShrubDecoctionHalf a glass daily for a weekInvestigatedSyphilis, intestinal problems, induction of labour[10, 28]
Clerodendrum rotundifolium Oliv.KisekesekeRoots/leavesShrubFresh leaf extract/root decoctionHalf a glass daily for a 5 daysInvestigatedDiabetes[10]
Hoslundia opposita Vahl.KamunyeLeavesHerbDecoctionHalf a glass 3 times a day for a week; bathInvestigatedUlcers[8, 10, 25]
Leonotis nepetifolia Schimp. exBenthKifumufumuWhole plantHerbDecoctionA glassful thrice a day for 3 daysInvestigatedHeadache[10, 21]
Ocimum basilicumEmopimLeavesHerbInfusionHalf a glass 3 times a day for a weekInvestigatedFever, eye cataract[23, 27]
Ocimum gratissimum Willd.MujaajaLeavesHerbDecoctionHalf a glass 3 times a day for 5 daysInvestigatedWounds, ear infections, chest pain[10, 21]
Ocimum lamiifolium Hochst.OmwenyiLeavesDecoctionHalf a glass 3 times a day for a weekInvestigatedAbdominal pain[19]
Plectranthus barbatusEbiriri omutanoWhole plant/leaves, roots/stemHerbInfusionOral, dose not specifiedInvestigatedFever, heart disease, snake bite[10, 23]
Plectranthus caninus RothKibwankulataLeavesHerbDecoction4 and 2 teaspoons thrice a day for adults and children, respectively, for a weekNo record[10]
Plectranthus cf. forskohliiEkizeraLeavesDecoctionOral, dose not specifiedNo record[19]
Rosmarinus officinalis L.RosemaryLeavesHerbDecoctionHalf a glass twice a day for 5 daysInvestigatedChest pain[10]
Tetradenia riparia (Hochst.) CoddKyewamalaLeavesHerbDecoctionOne teaspoon twice a day for a weekInvestigated[10]
LauranceaePersea americana Mill.OvakedoLeavesTreeDecoctionOral, dose not specifiedInvestigatedFungal and bacterial infection, high blood pressure, intestinal worms and parasites[23]
LoranthaceaeTapinanthus constrictiflorus (Engl.) DanserEnzirugazeLeavesHerbDecoctionA glass daily for 7 daysNo record[10]
MalvaceaeHibiscus surattensis L.Nantayitwako musotaLeavesShrubDecoctionHalf a glass thrice a day for 7 daysNo recordHigh blood pressure[10]
MeliaceaeAzadirachta indica A. Juss.NeemLeavesTreeDecoctionAbout 120 ml once a day for 7 daysInvestigatedDental decay/ache, yellow fever, cough, skin diseases, diabetes, nausea[10, 19, 23, 25]
Carapa grandiflora SpragueOmukeeteLeaves/barkTreeDecoctionHalf a glass twice a day for 7 daysNo record[10]
Melia azedarachEliraLeavesTreeDecoctionOral, dose not specifiedInvestigatedFever, skin disease, itching wounds, parasitic worms[23]
MenispermaceaeCissampelos mucronata A. Rich.KavawalaLeaves/whole plantHerbDecoctionHalf a glass twice a day for 5 daysInvestigated[10]
MimosaceaeAcacia hockii De willdEkisimRootsTreeDecoctionOral, dose not specifiedNo recordDiarrhea, syphilis, dysentery[23, 30]
Acacia niloticaInvestigated[31]
Acacia sieberianaEtiririRootsTreeDecoctionOral, dose not specifiedNo recordDysentery, epilepsy, cough[21, 23]
Albizia coriaria Welw.LugavuBarkTreeDecoction1 and 3 teaspoons thrice a day for children and adults, respectively, for a week.InvestigatedSkin diseases, diarrhea[10]
Albizia grandibracteata TaubeNongoBarkTreeDecoctionHalf a glass once a day for a weekInvestigatedYellow fever, anemia, fungal infections of scalp[8, 10, 32]
Albizia zygia (DC.) Macbr.MulongoBarkTreeInvestigated[21]
Newtonia buchananii (Baker) Gilb. & Perr.MpewereBarkTreeDried, powdered, added to boiling waterHalf a glass once a day for a weekNo record[10]
MoraceaeAntiaris toxicaria Lesch.KirunduBarkTreeDecoctionHalf a glass once a day for a weekInvestigatedWeakness in pregnancy, headache[8, 10]
Ficus natalensis HochstTreeInvestigatedGonorrhea[8, 33]
Ficus saussureana DC.MuwoBarkTreeDecoctionHalf a glass thrice a day for 7 daysNo record[10]
Milicia excels (Welw.) C. C. Berg.MivuleBarkTreeDecoctionHalf a glass thrice a day for 7 daysInvestigatedBurns, fresh cuts, skin rush[8, 10]
MoringaceaeMoringa oleifera LamMoringaLeaves/rootsTreeDecoction/chewed rawA glassful thrice a day for 7 days; a handful of fresh leaves chewed 3 times for 4 daysInvestigatedJoint pains[21, 25]
MusaceaeMusa paradisiaca (NC)KabalagalaLeavesHerbDecoctionOral, dose not specifiedInvestigatedJaundice, prolonged embryo in uterus[19]
MyricaceaeMyrica kandtiana Engl. (NC)OmujeejeLeavesDecoctionOral, dose not specifiedNo recordVomiting, diarrhea[19]
MyristicaceaePycnanthus angolensis (Welw.)Warb.LunabaLeavesTreeDecoctionHalf a glass a dayInvestigated[10]
MyrsinaceaeMaesa lanceolata Forssk.KiwondowondoLeavesShrubDecoctionHalf a glass thrice a day for 7 daysInvestigatedFebrile convulsions[10, 19, 24]
MyrtaceaeEucalyptus grandis Maiden.KalitunsiLeavesTreeDecoctionHalf a glass a dayNo recordCough[8, 10]
Psidium guajava L.MupeeraLeavesTreeDecoctionHalf a glass thrice a day for a weekInvestigatedBloody diarrhea, typhoid, wounds, cough[10, 23]
Syzygium cordatum Hochst.MugeegeBarkTreeDecoctionOral, dose not specifiedInvestigatedDry cough, skin rush, wounds[8, 10, 20, 29]
Syzygium cumini (L.) SkeelsJambulaLeavesTreeDecoctionHalf a glass thrice a day for a weekInvestigatedCough[32]
Syzygium guineense (Willd.) DC.KalunginsanvuBarkTreeDecoctionOral, dose not specifiedInvestigated[20]
PapillionaceaeButyrospermuum paradoxumEkunguriRootsTreeDecoctionOral, dose not specifiedNo recordLabour pains, headaches[23]
Ormocarpum trachycarpumEderutRootsShrubDecoctionOral, dose not specifiedNo recordPneumonia, snake bite[23]
PassifloraceaePassiflora edulis SimsAkatundaLeavesHerbFresh extractOral, dose not specifiedNo recordDiarrhea, cough[19]
PittosporaceaePittosporum brachcalyaNot definedNot definedShrubNo record[34]
Pittosporum mannii Hook. f. Subsp. ripicola (J. Leon)Cuf.MubajjankonLeavesShrubInfusion/decoctionHalf a glass a day for a weekNo record[10]
PoaceaeCymbopogon citratus Stapf.KisubiLeavesGrassDecoction120 ml every after 8 hours for a weekInvestigatedDental caries, influenza, cough, cancer, indigestion, fever[10, 19, 23]
Digitaria scalarum Chiov.LumbuguLeavesGrassDecoction120 ml every after 8 hours for a weekNo record[10]
Imperata cylindrical (L.) Beauv. var. africana (Anderss.) C. E. HubbardLusenkeRootsGrassDried, powdered, added boiling water/decoction120 ml once a day for a weekNo recordAbdominal pain[10]
Zea mays L.Luyange lwakasoliFlowers/husksCereal grassDecoction120 ml every after 8 hours for a weekInvestigatedBoosts immunity[10]
PolygalaceaeSecuridaca longipedunculata Fresen.EliloiRootsShrubDecoctionOral, dose not specifiedInvestigatedSkin diseases, measles, cough, hernia, diarrhea[23]
Maesopsis eminii Engl.MusiziBarkTreeDecoctionHalf a glass thrice a day for a weekNo record[10]
PortulacaceaeTalinum portulacifolium (Forssk.) Asch. ex Schweinf.MpoziaLeavesHerbOral, dose not specifiedNo record[21]
RosaceaePrunus africana (Hook. f.) KalkmanNtaseesa or NgwabuzitoBarkTreeDecoction2 and 3 teaspoons thrice a day for children and adults, respectively, for a weekInvestigatedFainting, cancer[8, 10]
Rubus steudneri schweinf.NkeneneLeavesHerbDecoctionHalf a glass once a day for a weekNo record[10]
RubiaceaeCoffea canephora FroehnerMwanyiLeavesShrubDecoctionOral, dose not specifiedNo record[21]
Hallea rubrostipulata (K. Schum.) J.-F. LeroyMuzikuBarkTreeDecoctionOral, dose not specifiedInvestigated[20]
Pentas longiflora Oliv.IshagaraLeavesDecoctionOral, dose not specifiedInvestigatedFever[19]
Vangueria apiculata K. Schum.MatugundaBarkShrubDecoction2 and 3 teaspoons thrice a day for children and adults, respectively, for a weekNo record[10]
RutaceaeCitrus reticulataOmuqugwaRootsTreeDecoctionOral, dose not specifiedInvestigatedWeight loss induction, cancer, skin diseases[23]
Citrus sinensisOmucungwa/cungwaRootsTreeDecoctionOral, dose not specifiedInvestigatedVomiting, cough, diabetes[21, 23, 25]
Teclea nobilis DelileOmuzoAerial partsDecoctionOral, dose not specifiedInvestigatedBody cleanser[32]
Toddalia asiatica Baill.KawuleRootsClimberDecoctionHalf a glass thrice a day for a weekInvestigatedCough, abdominal pain[10, 19, 24]
Zanthoxylum chalybeum Engl.Ntale ya ddunguRootsTreeDecoctionOral, dose not specifiedInvestigatedBody swellings, stomach ache, cough, fever, chest pain[10, 23, 28]
Zanthoxyllum leprieurii Guill. & Perr.Mutatembwa/munyenyeBarkTreeDecoction drunkHalf a glass thrice a day for a weekNo record[10]
SalicaceaeTrimeria grandifolia ssp. tropica (Hochst.) Warb.OmwatanshareLeavesDecoctionOral, dose not specifiedInvestigated[19]
SapindaceaeBlighia unijugata BakerNkuzanyanaBarkTreeDecoction drunkHalf a glass twice a day for a weekInvestigatedWounds, vomiting, skin diseases, fibroids, cervical cancer[8, 10]
SapotaceaeManilkara obovata (Sabine & G. Don)NkunyaBarkTreeDecoctionOral, dose not specifiedNo record[20]
ScrophulariaceaeSopubia ramosa (Hochst.) Hochst.KakulunkanyiWhole plantHerbDecoctionOral, dose not specifiedNo record[20]
SimaroubaceaeHarrisonia abyssinica Olive.EkeroiRoots/leavesShrubDecoctionOral, dose not specifiedInvestigatedFever, wounds, syphilis, snake bite, abdominal pain[23]
SolanaceaeDatura stramonium Thunb.AmaduduLeavesHerbDecoction drunkHalf a glass thrice a day for a weekNo recordUlcers, stomach ache, chest pain[10]
Physalis peruviana L.NtuntunuLeavesHerbDecoction drunkHalf a glass 3 times a day for a weekNo recordVomiting, febrile convulsions, fainting[8, 10, 19]
Solanum nigrum L.NsuggaLeavesHerbDecoction drunkHalf a glass 3 times a day for a weekInvestigatedEar infection, headache, epilepsy, STI, diarrhea[8, 10]
TiliaceaeTrumfetta rhomboidea Jacq.MusombankokoRootsShrubDecoction drunkHalf a glass once a day for a weekNo record[10]
UlmaceaeCeltis africana L.AkasisaLeavesTreeDecoction drunkHalf a glass a day for a weekInvestigated[10]
UmbelliferaeSteganotania araliacea HoeshstEmatuleRoots/leavesTreeDecoctionOral, dose not specifiedNo recordMeasles, body swelling[23]
VerbenaceaeLantana camaraKanpangaLeavesShrubDecoctionOral, dose not specifiedInvestigatedWounds, measles, tuberculosis, pneumonia, snake bite, chest pain[23]
Lantana trifolia L.OmuhukyeLeavesDecoctionOrally taken, dose not specifiedInvestigatedYellow fever, ringworms, muscle pain, prolapsed rectum[8, 19]
ZingiberaceaeCurcuma longa L.BinjaliRhizomeHerbFresh extract30 ml thrice a day for 3 daysInvestigated[28]


Plant familyPlant speciesLocal namePlant formMode of use to prevent malariaReference(s)

CleomaceaeCleome gynandra L.AkeyoHerbLeaves are cooked and eaten as a prophylactic measure[25]
CucurbitaceaeCucurbita maxima DuchesneAcugaScramblerLeaves cooked and pasted with groundnut then eaten[25]
EuphorbiaceaeManihot esculenta CrantzGwanaHerbTuber peelings are dried then burnt in house so that smoke repels mosquitoes[25]
FabaceaeCrotalaria ochroleuca G. DonAlayoHerbLeaves are cooked and eaten as a prophylactic measure[25]
LamiaceaeOcimum forsskaolii Benth.Yat colaHerbLeaves dried and burnt so that smoke chases away mosquitoes; bath infusion to repel mosquito[25]
Rosmarinus officinalis L.RosemaryHerbLeaves are cooked and eaten as a prophylactic measure; planted around the house to repel mosquitoes[10]
MalvaceaeGossypium hirsutum L.PamaShrubCotton lint is dried and burnt so that smoke keeps away mosquitoes[25]
MusaceaeMusa sp.Labolo kwonShrubFruit peeling are dried and burnt in the house to produce smoke that keeps away mosquitoes[25]
MyrtaceaeEucalptus grandis Maiden.KalitunsiTreeLeave and branches are burnt to repel mosquitoes[25]
PoaceaeCymbopogon citratus Stapf.KisubiGrassPlanted around the house to repel mosquitoes; taken in tea as a prophylactic measure[19, 23]
SolanaceaeSolanum americanum Mill.OcugaHerbLeaves are cooked and eaten as a prophylactic measure[25]

The mechanism of action of artemisinin is widely debated but the most accepted theory is that of activation of the molecule by heme, which enables it to produce free radicals that then destroy the proteins needed for parasite survival [36]. The presence of an uncommon chemical peroxide linkage bridge in artemisinin, a sesquiterpene lactone, is the most probable reason for its antimalarial effects. Cleavage of the peroxide linkage bridge in the presence of iron (II) ions (from heme) forms very reactive free radicals that undergo rapid rearrangement to form more stable carbon-centered radicals, which chemically modify the parasite and inhibit various processes within the parasite molecules, resulting in its death [36]. Artemisinin acts on primarily the trophozoite parasitic phase and prevents disease progression. It kills circulating ring-stage parasites, thus increasing the therapeutic response [37]. Mok et al. [38] suggested that artemisinin is linked to the upregulation of unfolded protein response pathways, which leads to decreased parasitic growth and development. Shandilya et al. [39] suggested that artemisinin is activated by iron, which then functionally inhibits PfATP6, a calcium pump, by terminating phosphorylation, nucleotide binding, and actuator domains, eventually leading to a functional loss of PfATP6 of the Plasmodium parasite and its death. A study by Mbengue et al. [40] indicated that artemisinin strongly inhibits phosphoinositide-3-kinase (PfPI3K), an enzyme important in cellular activities including growth, multiplication, differentiation, and survival in P. falciparum.

Cinchona tree bark, from which quinine was isolated, has been used to treat malaria since 1632 [41]. The World Health Organization listed quinine as one of the important medicines needed in a health system [42]. It is however only used to treat malaria caused by chloroquine-resistant strain of P. falciparum in the absence of artemisinins [43]. A popular hypothesis about the mechanism of action of quinine is based on chloroquine, another quinoline drug which is closely linked to quinine and has been comprehensively studied. Quinine inhibits the pathway of biocrystallization of hemozoin, resulting in the accumulation of the free cytotoxic heme which eventually kills the parasite [44].

Most of the plants used in the treatment of malaria in Uganda contain alkaloids greatly implicated in antiplasmodial activity (Table 3). A number of alkaloids target apicoplast, an organelle in the Plasmodium parasite, while others such as benzylisoquinoline alkaloids in Cissampelos mucronata, a plant belonging to the family Menispermaceae inhibits protein synthesis in the parasite [99].


Plant familyScientific namePart usedExtracting solventMeans of traditional extractionReport on antiplasmodial, IC50 (μg/ml)/antimalarial activity (Plasmodium strain)Active chemical constituentsReference(s)

AcanthaceaeJusticia betonica L.ShootMethanolHot water69.6 (chloroquine sensitive, K39)Justetonin (indole(3,2-b) quinoline alkaloid glycoside)[20]
Water>100 (chloroquine sensitive, K39)
AloeaceaeAloe dawei A. Berger (wild/cultivated)LeavesEtherCold water; mashing; hot waterExtract had anti-P. falciparum activity value of 7.97 (95% CI: 3.56 to 17.85) μg/ml with 50% schizonts suppression per 200 WBC (EC50)Anthraquinones, aloin, lectins,[19, 45]
Aloe kedongensis (wild)LeavesMethanolHot water87.7 (chloroquine sensitive, D6); 67.8 (chloroquine resistant, W2)Anthrone, C-glucoside homonataloin, anthraquinones, aloin, lectins[19, 46]
Aloe ferox MillLeavesDichloromethaneWater21 (chloroquine sensitive, D10)Mannans, polymannans, anthraquinones, aloin, lectins, anthrones[19, 31, 47]
Water>100 (chloroquine sensitive, D10)
AnacardiaceaeMangifera indica L.LeavesChloroform:Methanol (1 : 1)Hot waterInhibited growth of P. falciparum by 50.4% at 20 μg/mlPhenolics[48, 49]
Stem barkEthanol>50 (chloroquine resistant, FcB1)
Rhus natalensis Bernh. Ex KraussLeavesEthanolHot water6.6 (P. falciparum)Triterpenoids[24]
ApiaceaeCentella asiatica (L.) Urb.Whole plantWaterWater58.6 (chloroquine sensitive, D6); not detected (chloroquine resistant, W2)Phenolics and flavonoids[50]
ApocynaceaeAlstonia boonei De Wild.Stem barkWaterHot water80.97% suppressive activity at 200 mg/kg (P. berghei) in combination with other two local herbs.Alkaloids, triterpenoids[51]
Carissa edulis (Forssk.) VahlStem barkDichloromethaneMashing; hot water33 (chloroquine sensitive, D10)Lignan, nortrachelogenin[52]
Carissa spinarum Lodd. ex A. DC.Root barkMethanolHot water14.5 (chloroquine sensitive, D6)Saponins, sesquiterpenes[53]
Catharanthus roseus G. DonLeavesMethanolHot water4.6 (chloroquine sensitive, D6); 5.3 (chloroquine resistant, W2)Alkaloids, terpenoids, flavonoids, esquiterpenes[54]
AristolochiaceaeAristolochia elegans Mast.SeedsMethanolWater>50 (chloroquine sensitive, 3D7); undetectable (chloroquine resistant, W2)Sesquiterpenoids, diterpenoids, monoterpenoids, alkaloids[19, 55]
AsphodelaceaeAloe vera (L.) Burm. f.LeavesWaterCold water; mashing; hot waterAntiplasmodial activity in terms of EC50 values 0.289 to 1.056 μg/ml (chloroquine sensitive)Aloin, anthraquinones, aloe-emodin[56]
AsteraceaeAgeratum conyzoides L.Whole plantMethanolHot water11.5 (chloroquine sensitive, D6); 12.1 (chloroquine resistant, W2)Flavonoids[54]
Artemisia annua L.LeavesWaterHot water1.1 (chloroquine sensitive, D10); 0.9 (chloroquine resistant, W2)Sesquiterpenes and sesquiterpene lactones including artemisinin, flavonoids such as chrysoplenol-D, eupatorin, chyrsoplenetin[19, 57]
Artemisia afra Jacq. Ex WilldLeavesMethanolHot water9.1 (chloroquine sensitive, D6); 3.9 (chloroquine resistant, W2)Acacetin, genkwanin, 7-methoxyacacetin[54]
Aspilia africana (Pers.) C. D. AdamsLeavesEthanolHot waterSignificant chemo suppressive effect of 92.23% (400 mg/kg) on P. bergheiSaponins, terpenoids, alkaloids, resins, tannins, flavonoids, sterols[19, 58]
Baccharoides adoensis (Sch. Bip. ex Walp.) H. Rob.LeavesPetroleum etherHot water4.6 (chloroquine resistant, K1)Flavonoids[26]
Aspilia africana L.LeavesDichloromethaneHot water; mashing8.5 (chloroquine sensitive, D10)Flavonoids including quercetin 3,3′-dimethyl ether 7-0-α-L-rhamnopyranosyl-(1 ⟶ 6)-β-D-glucopyranose and quercetin 3,3′-dimethyl ether 7-0-β-D-glucopyranose[52]
Bothriocline longipes N. E. Br.LeavesChloroformHot water3.7 (P. falciparum)5-alkylcoumarins,[19, 24]
Ethanol50 (P. falciparum)
Crassocephalum vitellinumLeavesEthyl acetateHot water40.6% inhibition of P. falciparum at 10 μg/mlFlavonoids[32]
Guizotia scabra Chiov.Whole plantCrude ethanolHot water49.09% growth inhibition at 100 μg/ml (chloroquine resistant, Dd2)Lactones, eudesmanoline[59]
Melanthera scandens (Schumach. & Thonn.) RobertyLeavesChloroformHot water68.83% chemo suppression activity (P. berghei)Triterpenoid saponins[60]
Microglossa pyrifolia (Lam.)O. KtzeLeavesHot water<5 (both chloroquine sensitive, NF54 and resistant, FCR3)E-phytol; 6e-geranylgeraniol-19-oic acid[2, 28]
Schkuhria pinnata (lam.)Whole plantWaterHot water22.5 (chloroquine sensitive, D6); 51.8 (chloroquine resistant, W2)Schkuhrin I and schkuhrin II[54]
Methanol1.3 (chloroquine sensitive, D6); 6.8 (chloroquine resistant, W2)
Solanecio mannii (Hook. f.) C. JeffreyLeavesMethanolWater21.6 (chloroquine sensitive, 3D7); 26.2 (chloroquine resistant, W2)Phytosterols, n-alkanes and N-hexacosanol,[19, 55]
Tagetes minuta L.LeavesEthyl acetateWater61.0% inhibition of P. falciparum at 10 μg/ml[32]
Tithonia diversifolia A. GrayLeavesMethanolWater1.2 (chloroquine sensitive, 3D7); 1.5 (chloroquine resistant, W2)Tagitinin C, sesquiterpene lactones[55]
Vernonia adoensis Sch. Bip. ex Walp.LeavesMethanolHot water83.4% inhibition of parasitaemia, at 600 mg/kg (P. berghei)Glycocides, glaucolides[19, 61]
Vernonia amygdalina DelileLeavesMethanol/dichloromethaneHot water; cold water2.7 (chloroquine resistant, K1)Coumarin, sesquiterpene lactones including vernolepin, vernolin, vernolide, vernodalin and hydroxyvernodalin, steroid glucosides[19, 26]
Vernonia cinerea (L.) Less.Whole plantWaterHot water>50 (chloroquine sensitive, 3D7); 37.2 (chloroquine resistant, K1)Sesquiterpene lactone[62]
Vernonia lasiopus O. Hoffm.LeavesMethanolMashing; hot water44.3 (chloroquine sensitive, D6); 52.4 (chloroquine resistant, W2)Sesquiterpene lactones, polysaccarides[19, 54]
BignoniaceaeMarkhamia lutea (Benth.) K. Schum.LeavesEthyl acetateHot water71% inhibition of P. falciparum at 10 μg/mlPhenylpropanoid glycosides, cycloartane triterpenoids[32]
Spathodea campanulata Buch.-Harm. ex DC.Stem barkEthyl acetateWater28.9% inhibition of P. falciparum at 10 μg/mlQuinone (lapachol)[32]
CaesalpiniaceaeCassia didymobotrya Fres.LeavesMethanolHot water23.4 (chloroquine sensitive, D6); undetectable (chloroquine resistant, W2)Alkaloids[54]
Erythrophleum pyrifoliaLeavesEthanolHot water>50 (P. falciparum)[24]
Senna spectabilis (DC.) H. S. Irwin & BarnebyLeavesEthanolWater59.29% growth inhibition at 100 mg/kg body weight dose (P. berghei)Piperidine alkaloids[63]
CaesalpinioideaeCassia hirsutaRoot backMethanolWater32.0 (chloroquine sensitive 3D7)[64]
CanelliaceaeWarbugia ugandensis SpragueStem backMethanolHot water6.4 (chloroquine sensitive, D6); 6.9 (chloroquine resistant, W2)Sesquiterpenes e.g. muzigadiolide[27, 54]
Water12.9 (chloroquine sensitive, D6); 15.6 (chloroquine resistant, W2)
CaricaceaeCarica papaya L.LeavesEthyl acetateHot water2.96 (chloroquine sensitive, D10); 3.98 (chloroquine resistant, DD2)Alkaloids, saponins, tannins, glycosides[65]
Methanol10.8 (chloroquine sensitive, D10)
CelastraceaeMaytenus senegalensisRootsHot water1.9 (chloroquine sensitive, D6); 2.4 (chloroquine resistant, W2)Terpenoids, pentacyclic triterpenes e.g. pristimerin[66]
ChenopodiaceaeChenopodium ambrosioides L.LeavesCrude hydroalcoholic extractHot waterInhibited the P. falciparum growth, exhibiting an IC50 of 25.4 μg/mlSesquiterpenes, monoterpenes[67]
CombretaceaeCombretum molle G. DonStem backAcetoneWater8.2 (chloroquine sensitive 3D7)Phenolics, punicalagin[68]
CucurbitaceaeCucurbita maxima Lam.SeedsCrude ethanolHot water50% reduction of parasitaemia levels in P. berghei infected mice at 500 mg/kg.Phenols, terpenoids, alkaloids, tannins[69]
Momordica foetida Schumach.ShootWaterHot water6.16 (chloroquine sensitive, NF54); 0.35 (chloroquine resistant, FCR3)Saponins, alkaloid, cardiac glycosides[28]
EbenaceaeEuclea latideus StaffRoot backHexaneWater38.2 (chloroquine sensitive, 3D7); 38.9 (chloroquine resistant, Dd2)Triterpenoids lupeol, betulin, 3β-(5-hydroxyferuloyl)lup-20(30)-ene[23]
EuphorbiaceaeAlchornea cordifolia (Schumach.) Mull. Arg.LeavesWaterHot water4.8 (chloroquine resistant, K1)Phenolics including ellagic acid[70]
Bridelia micrantha Baill.Stem barkMethanolHot water19.4 (chloroquine sensitive, D6); 14.2 (chloroquine resistant, W2)[50]
Clutia abyssinica Jaub. & SpachLeavesMethanolWater7.8 (chloroquine sensitive, D6); 11.3 (chloroquine resistant, W2)Diterpenes[54]
Croton macrostachyus Olive.LeavesChloroformHot waterChemotherapeutic effect of 66–82% in malaria mouse modelTriterpenoids including lupeol[71]
Fluegea virosa (Roxb. ExWillb.)VoigtLeavesWater/methanolHot water2 (chloroquine resistant, W2)Bergenin[72]
Jatropha curcas L.LeavesEthyl acetateHot water5.1 (chloroquine sensitive, NF54); 2.4 (chloroquine resistant, K1)Alkaloids, saponnins, glycosides, tannins[73]
Phyllanthus (pseudo) niruri Mull. Arg.WaterHot waterRanged from 2.9 to 4.1 (both chloroquine sensitive, 3D7 and resistant, Dd2)Coumarins including 1-O-galloyl-6-O-luteoyl-a-D-glucose[74]
FabaceaeCajanus cajan (L.) DruseLeavesCrude ethanolMashing29.0 (P. falciparum)Cajachalcone;[75]
Entada abyssinica Steud. ex A. Rich.SeedsMethanolHot water>5 (chloroquine resistant, K1)Flavonoids, terpenoids[26, 32]
Entada africana Guill. & Perr.LeavesEthanolHot water26.4 (chloroquine sensitive, HB3); 28.9 (chloroquine resistant, FcM29)Phenolics[76]
Erythrina abyssinica Lam.Stem barkEthyl acetateHot water83.6% inhibition of P. falciparum at 10 μg/mlChalcones (5-prenylbutein, homobutein), flavanones including 5-deoxyabyssinin II, abyssinin III and abyssinone IV[32]
Indigofera emerginella Steud. ex A. RichLeavesEthanolHot water5.8 (P. falciparum)[24]
Senna didymobotrya (Fresen.) H. S. Irwin & BarnebyLeavesMethanolHot water>100 (chloroquine sensitive, K39)Quinones[20, 29]
Senna siamea (Lam.) H. S. Irwin & BarnebyLeavesEthanolMashing; hot water28.8 (chloroquine sensitive, 3D7); 48.3 (chloroquine resistant, W2)Phenolic derivative, chrobisiamone a, anhydrobarakol[77]
Tamarindus indica L.Stem barkWaterHot water25.1% chemo suppressive activity at 10 mg/kg (P. berghei)Saponins (leaves), tannins (fruits)[78]
FlacourtiaceaeTrimeria bakeri Gilg.LeavesPetroleum etherHot water3.9 (P. falciparum)Triterpenoids[24]
HypericaceaeHarungana madagascariensis Lam.Stem barkWaterHot water9.64 (chloroquine resistant, K1)Quinones including bazouanthrone, feruginin a, harunganin, harunganol a[70]
LamiaceaeAjuga remota Benth.Whole plantEthanolHot water55 (chloroquine sensitive, FCA/GHA); 57 (chloroquine resistant, W2)Ajugarin-1, ergosterol-5,8-endoperoxide, 8-O-acetylharpagide, steroids[79]
Clerodendrum myricoides R. Br.Root barkMethanolHot water4.7 (chloroquine sensitive, D6); 8.3 (chloroquine resistant, W2)[50, 80]
Clerodendrum rotundifolium Oliv.LeavesMethanolMashing; hot water<5 (both chloroquine sensitive, NF54 and resistant, FCR3)Saponins, tannins[28]
Hoslundia opposita Vahl.LeavesEthyl acetateHot water66.2% inhibition of P. falciparum at 10 μg/mlQuinones, saponins, abietane diterpenes (3-O-benzoylhosloppone)[32]
Leonotis nepetifolia Schimp. exBenthLeavesEthyl acetateWater27.0% inhibition of P. falciparum at 10 μg/ml[32]
Ocimum basilicumLeavesEthanolHot water68.14 (chloroquine sensitive, CQ-s); 67.27 (chloroquine resistant, CQ-r)[50, 80]
Ocimum gratissimum Willd.Leaves/twigsDichloromethaneHot water8.6 (chloroquine resistant, W2)Flavonoids[47, 49]
Ocimum lamiifolium Hochst.LeavesWaterWaterSignificantly suppressed parasitaemia, 22.2%, 26.8% and 35.5% at dose of 200, 400 and 600 mg·kg, respectively (P. berghei)[81]
Plectranthus barbatusLeaves/stemDichloromethaneHot waterNo activity[23, 47]
Rosmarinus officinalis L.Hot waterEssential oil at a concentration 15867 ng/ml had no antimalarial activity[82]
Tetradenia riparia (Hochst.) CoddRootHot water13.2 (chloroquine-sensitive, NF54)[83]
LauranceaePersea americana Mill.LeavesEthanolHot water10.15 (chloroquine sensitive, 3D7); 44.94 (chloroquine resistant, W2)Phenolics[84]
MeliaceaeAzadirachta indica A. Juss.LeavesHot water17.9 (chloroquine sensitive, D6); 43.7 (chloroquine resistant, W2)Terpenoids, isoprenoids, gedunin[49, 66]
Melia azedarachLeavesMethanolHot water55.1 (chloroquine sensitive, 3D7); 19.1 (chloroquine resistant, W2)[85]
MenispermaceaeCissampelos mucronata A. Rich.Root barkMethanolHot water8.8 (chloroquine sensitive, D6); 9.2 (chloroquine resistant, W2)Benzylisoquinoline alkaloids[80]
MimosaceaeAcacia niloticaStem barkMethanolHot waterDose of 100 mg/kg b/w produced parasitic (P. berghei) inhibition 77.7%Tannins, flavonoids, terpenes[86]
Albizia coriaria Welw.Stem barkMethanolHot water15.2 (chloroquine sensitive, D6); 16.8 (chloroquine resistant, W2)Triterpenoids, lupeol, lupenone[54]
Albizia grandibracteata TaubeLeavesEthyl acetateHot water22.0% inhibition of P. falciparum at 10 μg/ml[32]
Albizia zygia (DC.) Macbr.Stem barkMethanolWater1.0 (chloroquine resistant, K1)Flavonoids mainly 3′,4′,7-trihydroxyflavone[87]
MoraceaeAntiaris toxicaria Lesch.Stem barkEthyl acetateHot water36.4% inhibition of P. falciparum at 10 μg/ml[32]
Ficus natalensis HochstLeavesHexaneHot water6.7 (P. falciparum)[88]
Milicia excels (Welw.) C. C. Berg.LeavesEthanolHot water76.7% chemo suppressive activity at 250 mg/kg/day (P. berghei)[89]
MoringaceaeMoringa oleifera LamLeavesMethanolMashing; hot water9.8 (chloroquine sensitive, D6); not detected (chloroquine resistant, W2)Flavonols[49, 80]
MusaceaeMusa paradisiaca (NC)LeavesEthyl acetateHot water75 (chloroquine sensitive, 3D7); 100 (chloroquine resistant, Dd2)Flavonoids[49, 90]
MyristicaceaePycnanthus angolensis (Welw.)Warb.Leaves50% ethanolHot water>1000 (chloroquine sensitive, 3D7)Talaumidin[91]
MyrsinaceaeMaesa lanceolata Forssk.TwigDichloromethane:Methanol (1 : 1)Hot water5.9 (chloroquine sensitive, D10)Lanciaquinones, 2,5, dihydroxy-3-(nonadec-14-enyl)-1,4-benzoquinone[24, 52, 55]
MyrtaceaePsidium guajava L.Stem backWaterHot water10–20 (chloroquine sensitive, D10)Phenols, flavonoids, carotenoids, terpenoids[49, 92]
Syzygium cordatum Hochst.TwigDichloromethane:Methanol (1 : 1)Hot water14.7 (chloroquine sensitive, D10)[55]
Syzygium cumini (L.) SkeelsStem backHot water0.25 to 27.1 (chloroquine-resistant strains)[93]
Syzygium guineense (Willd.) DC.LeavesCrude ethanolHot water49.09% chemo suppression at 400 mg/kg (P. berghei)[94]
PoaceaeCymbopogon citratus Stapf.Whole plantHot water99.89% suppression of parasitaemia at 1600 mg/kgFlavonoids[20, 49, 95]
Zea mays L.HusksEthyl acetateHot water9.3 (chloroquine sensitive, 3D7); 3.7 (chloroquine resistant, INDO)Alkaloids, flavonoids and triterpenoids[96]
PolygalaceaeSecuridaca longipedunculata Fresen.LeavesDichloromethaneHot water6.9 (chloroquine sensitive, D10)Saponins, flavonoids, alkaloids, steroids[92]
RosaceaePrunus africana (Hook. f.) KalkmanStem barkMethanolHot water17.3 (chloroquine sensitive, D6); not detected (chloroquine resistant, W2)Terpenoids[54]
RubiaceaeHallea rubrostipulata (K. Schum.) J.-F. LeroyRootEthanolWater100 μg/ml extract had 65.54% growth inhibition (chloroquine resistant, Dd2)Alkaloids[59]
Pentas longiflora Oliv.RootMethanolHot water0.99 (chloroquine sensitive, D6); 0.93 (chloroquine resistant, W2)Pyranonaphthoquinones, pentalongin (1) and psychorubrin (2), naphthalene derivative mollugin (3)[97]
RutaceaeCitrus reticulataSeeds (isolimonexic acid methyl ether)Hot water<4.76 (both chloroquine sensitive, D6 and resistant, W2)Limonin, isolimonexic acid methyl ether, ichangin, deacetylnomilin, obacunone[98]
Citrus sinensis70% ethanolHot water53.27% suppression of parasitaemia at 700 mg/kgTannins, alkaloids, saponins, flavonoids[20, 24, 99]
Teclea nobilis DelileBarkEthyl acetateWater54.7% inhibition of P. falciparum at 10 μg/mlQuinonline alkaloids[32]
Toddalia asiatica Baill.Root barkMethanolWater6.8 (chloroquine sensitive, D6); 13.9 (chloroquine resistant, W2)Furoquinolines (nitidine, 5,6-dihydronitidine), coumarins[80]
Zanthoxylum chalybeum Engl.Stem barkWaterHot water4.3 (chloroquine sensitive, NF54); 25.1 (chloroquine resistant, FCR3)Chelerythine, nitidine, methyl canadine[28]
SalicaceaeTrimeria grandifolia ssp. tropica (Hochst.) Warb.LeavesMethanolHot water>50 (chloroquine sensitive, 3D7)[55]
SapindaceaeBlighia unijugata BakerLeavesEthyl acetateHot water2.3% inhibition of P. falciparum at 10 μg/ml[32]
SimaroubaceaeHarrisonia abyssinica Olive.RootsHot water4.4 (chloroquine sensitive, D6); 10.25 (chloroquine resistant, W2)Limonoids, steroids[66]
SolanaceaeSolanum nigrum L.FruitMethanolHot water10.3 (chloroquine sensitive, 3D7); 18.7 (chloroquine resistant, K1)Steroidal alkaloids, flavonoids[100]
UlmaceaeCeltis africana L.Stem barkEthyl acetateHot water37.5% inhibition of P. falciparum at 10 μg/ml[32]
VerbenaceaeLantana camaraLeavesDichloromethaneHot water8.7 (chloroquine sensitive, 3D7); 5.7 (chloroquine resistant, W2)Sesquiterpenes, triterpenes, flavonoids[30]
Lantana trifolia L.Arial partsPetroleum etherHot water13.2 (P. falciparum)Steroids, terpenoids, alkaloids, saponins[24]
Ethanol>50 (P. falciparum)
ZingiberaceaeCurcuma longa L.Hot water; mashing5 mg/kg had a significantly high chemo suppressive activity of 56.8% (P. berghei)Polyphenolic curcumin[101]

Flavonoids in a vast number of plants used for malaria treatment in Uganda are common to plants in the family Asteraceae such as B. longipes, A. conyzoides, and A. africana although other herbal plants from different families including C. roseus in Apocynaceae and A. zygia and A. nilotica in Mimosaceae also have them as active antiplasmodial constituents (Table 3). Flavonoids exhibit great antiplasmodial activity against different strains of the malaria parasite although the mechanism of antimalarial action is not clear [99]. Some studies suggest that flavonoids impede the influx of myoinositol and L-glutamine in erythrocytes that are infected [99]. Some flavonoids increase the level of oxidation of erythrocytes and inhibit protein synthesis in malaria parasites [99]. Furthermore, flavonoids are believed to inhibit fatty acid biosynthesis (FAS II) in Plasmodium [102].

Artemisinin resistance in P. falciparum has been reported in Vietnam, Cambodia, Muang Lao, and Thailand. A report published in 2018 showed over 30 separate cases in Southeast Asia of artemisinin resistance [36]. In case of resistance, parasitic clearance is slowed down and gametocytemia increases, resulting in greater selective pressure on other partner drugs to which resistance increases, thereby posing a great health threat. Thus, it is very important that the discovery of other drugs with novel mechanisms of action be prioritized by extensive exploration of the huge medicinal plant resources in Africa, which have been used by locals for effective malaria treatment yet have never been scientifically investigated for their antimalarial potential. Amoa Onguéné et al. [35] emphasized that it was indeed Africa’s turn to offer a new antimalarial drug to humanity since artemisinin was discovered in Asia and quinine in Latin America.

5. Herbs and Plant Parts Used to Manage and Treat Malaria across Communities in Uganda

About 182 plant species from about 63 different plant families are used to treat malaria across several communities in Uganda (Table 1). Of the 63 plant families, species within the family Asteraceae are most widely used in the country to treat malaria, constituting up to 15% of all plant species used (Figure 3(a)). This is followed by species from Fabaceae (9%), Lamiaceae (8%), Euphorbiaceae (6%), and Mimosaceae (4%) families, with Myrtaceae, Aloeaceae, and Rutaceae families each contributing approximately 3% to the total number of species used for malaria treatment in Uganda (Figure 3(a)). The remaining families contribute only 49% of the total plant species used for malaria treatment (Figure 3(a)).

The plant parts greatly used to treat malaria are leaves (54.4%) followed by roots (17.4%) and bark (16%); whole plants and other plant parts are used less commonly (Figure 3(b)). A particular herbal plant is commonly used singly though some times in combination with other herbs. The most common way of use is by boiling the medicinal plant part in water and then drinking the decoction; ingestion of fresh extracts and powdered forms of the herbs is also practiced (Table 1).

Different herbal remedies are used in different communities in different parts of the country depending on the geographical distribution of the medicinal plant species, for example, Warburgia ugandensis is particularly used in the eastern part of Uganda. However, herbal plant species such as Bidens pilosa L. are spread throughout the country and thus well known for malaria treatment across the country. In a study conducted by Ssegawa and Kasenene [20], no tree species in the forests of southern Uganda were more useful than Hallea rubrostipulata and Warburgia ugandensis in the treatment of malaria. These medicinal plants are known by different local names in different parts of the country as Uganda has diverse ethnic groups, including the Luo, Baganda, Itesots, and Banyankole/Bakiga.

Among all communities in Uganda, some measures are taken to control malaria, including draining of stagnant water, clearing and burning bushes, sleeping under insecticide-treated mosquito nets, and house spraying with insecticides.

6. Mode of Preparation and Use of Herbs in Treatment of Malaria in Uganda

The mode of preparation and use of herbs among different communities vary depending on the nature of the herb and plant parts used for malaria treatment [10]. Most commonly, the herbal medicines are prepared as water extracts in the form of decoction and infusion or as steam baths (Table 1) [19, 23]. The herbal plant water extract is made mostly by boiling a handful of the medicinal plant parts such as leaves in a litre of water and then given to the patient to take orally (Table 1) [23]. The dose of the extract given is dependent on the age of the patient and the “strength” of the herbal medicine although occasionally the weight of the patient [19, 23]. The quantity of extract given ranges from 100 to 500 ml, 100 to 250 ml, and 1 to 3 tea or tablespoons for adults, older children, and young children below 5 years of age, respectively, between 1 and 3 times a day for about a week or until when patient has recovered [19, 25]. The extracts are mostly prepared from single herbal plants or from combination of two herbal plants, for example, a decoction of Tamarindus indica and Mangifera indica is common [25].

In some cases, the medicinal plant parts are dried then pulverized to powder and 2–5 tablespoons of the power added to water and boiled to make a decoction. Some medicinal plant parts such as bark of M. indica stem and roots of V. lasiopus and their powders are boiled for long until the water is half the initial amount [25]. The herbal plant powder can also be added to cold or hot water and stirred and then drunk as recommended [10].

Medicine for malaria treatment from a herb such as B. pilosa can be made by squeezing a handful of its freshly picked leaves and drinking 1–3 teaspoons of the extract a day (Table 1) [23]. Occasionally, malaria herbal medicines can be obtained by preparing different plant parts in combination, for example, an infusion can be made from fresh leaves and pounded fresh roots of V. amygdalina [25]. This is then taken orally in a recommended dose. A handful of medicinal plant parts such as leaves can be squeezed and mixed with cold or warm water for bath, for example, leaves of B. adoensis [25]. Some common herbs are also eaten as vegetables as a prophylactic measure against malaria while others are planted in pots around houses or burnt to drive away mosquitoes (Table 2).

7. Antimalarial Activities and Toxicity of Herbs Used in Uganda for Malaria Treatment

Some studies have been performed on antiplasmodial/antimalarial activities of some of the herbal plants used in Uganda to treat malaria by using various strains of malarial parasites to confirm effectiveness as malaria treatment [26, 28]. Furthermore, a broad range of phytochemicals responsible for biological activities in some of the antimalarial herbs have been isolated and identified [23]. Of the 182 plant species used in Uganda for the treatment of malaria, 112 plant species (64%) have been investigated for antimalarial activities, of which 108 plants showed positive results and only four plant species did not give positive results when tested for antimalarial activities (Table 1). For about 70 plant species (39%) that are used among different communities in Uganda for the treatment of malaria, there was no record of investigation for antimalarial activities (Table 1).

The antimalarial activity of herbal plants is due to the presence of a number of metabolically active compounds [23]. These compounds may occur in the form of alkaloids, sesquiterpenes, quinones, triterpenoids, flavonoids, quassinoids, limonoids, terpenes, chalcones, coumarins, or other miscellaneous forms [85]. The solvent of extraction largely determines the concentrations of the active metabolites in the extract. For example, methanolic extracts of the herbal plants are in general more active in vitro than water extracts probably due to the presence of higher amounts of more active lipophilic compounds (Table 3) [54].

The levels of activity of the antimalarial plant extracts depend on the concentration of the active antimalarial secondary metabolites [54]. For example, gedunin, a very active compound against Plasmodium present in leaves of A. indica had an IC50 of 0.02 μg/ml against P. falciparum, but its concentration in the plant is in very low and thus moderate activity of its extract (Table 3) [23, 54].

The synergistic effect of the interaction of the different active secondary metabolites is a main contributing factor to the high levels of antiplasmodial activity of some of the herbal plant extracts, for example, in A. afra, none of the isolated flavonoids and sesquiterpenes had a high activity, yet the plant extract had an IC50 of 3.9 μg/ml against P. falciparum suggesting a synergistic effect of the compounds in the extract [54]. The presence of particular active compounds in the herbal plant extracts is key in enhancing its antimalarial property. The compound 6E-geranylgeraniol-19-oic-acid a diterpene isolated from M. pyrifolia aqueous extract was considered responsible for its antiplasmodial activity; nitidine isolated from Z. chalybeum had an IC50 as low as 0.17 μg/ml against P. falciparum 3D7 [10]; and pristimerin with an IC50 0.5 mg/ml against P. falciparum was the main active ingredient in M. senegalensis extract, making it have a very high antiplasmodial activity [54]. The presence of a moderate amount of a minimum of two secondary metabolites in the extract could explain the efficacy of the herbal extracts for malaria treatment [10]. The pathogenic strains used may be different for different in vitro studies; thus, resistance of the parasite to the active metabolites could cause a variation in the level of antimalarial activity of the extracts [10]. Herbal plants with no antiplasmodial activity suggest the absence of the metabolically active compounds against the Plasmodium parasites in their extracts [23]. Table 4 indicates a list of herbal plants used for malaria treatment in Uganda with high antiplasmodial activities (IC50μg/ml in one of its solvent extracts or high percentage inhibition of plasmodia) that could be potentially investigated further.


Plant familyPlant speciesPlant partExtracting solventReport on antiplasmodial, IC50 (μg/ml)/antimalarial activity (Plasmodium strain)Active chemical constituentsToxicity/safety informationReference(s)

AsteraceaeArtemisia afra Jacq. Ex WilldLeavesMethanol3.9 (chloroquine resistant, W2)Acacetin, genkwanin, 7-methoxyacacetinCytotoxicity was observed in Vero cells[54, 103]
Artemisia annua L.LeavesWater0.9 (chloroquine resistant, W2); 1.1 (chloroquine sensitive, D10)Sesquiterpenes and sesquiterpene lactones including artemisininGenerally safe and effective; nausea may occur on drinking herbal extract; artemisinin, an active compound in the extract is safe for pregnant women at least during second and third trimesters[19, 57, 104]
Aspilia africana (Pers.) C. D. AdamsLeavesEthanolSignificant chemo suppressive effect of 92.23% (400 mg/kg) on P. bergheiSaponins, terpenoids, alkaloids, resins, tannins, flavonoids, sterolsNo signs of toxicity in mice even at a dose as high as 5000 mg/kg[19, 58]
Jatropha curcas L.LeavesEthyl acetate2.4 (chloroquine resistant, K1)Alkaloids, saponnins, glycosides, tanninsModerate toxicity on thrombocyte line and a protective effect on cardiovascular system; no signs of toxicity in mice following oral administration of 5000 mg/kg body weight (bw) dose[73, 105]
Microglossa pyrifolia (Lam.)O. KtzeLeavesDichloromethane1.5 (chloroquine sensitive, 3D7; 2.4 chloroquin resistant, W2)E-phytol; 6e-geranylgeraniol-19-oic acidRelatively high cytotoxicity against cells from the human foetal lung fibroblast cell line[2, 28, 55]
Schkuhria pinnata (lam.)Whole plantMethanol1.3 (chloroquine sensitive, D6)Schkuhrin I and schkuhrin IIMethanol extract: low cytotoxicity against human cells; aqueous extracts: no observed toxicity observed in mice[32, 54]
Tithonia diversifolia A. GrayLeavesMethanol1.2 (chloroquine sensitive, 3D7); 1.5 (chloroquine resistant, W2)Tagitinin C, sesquiterpene lactonesAerial parts are cytotoxic against cells from the human foetal lung fibroblast cell line[55]
Vernonia amygdalina delileLeavesMethanol/dichloromethane2.7 (chloroquine resistant, K1)Coumarin, sesquiterpene lactones including vernolepin, vernolin, vernolide, vernodalin and hydroxyvernodalin, steroid glucosidesPetroleum ether extract shows strong cytotoxicity[19, 26, 32]
CaricaceaeCarica papaya L.LeavesEthyl acetate2.96 (chloroquine sensitive, D10); 3.98 (chloroquine resistant, DD2)Alkaloids, saponins, tannins, glycosidesNo serious toxicity reported, carpaine, an active compound against P. falciparum had high selectivity and was nontoxic to normal RBCs[65, 106]
CelastraceaeMaytenus senegalensisRoots1.9 (chloroquine sensitive, D6); 2.4 (chloroquine resistant, W2)Terpenoids, pentacyclic triterpenes, e.g., pristimerinNo toxicity observed in ethanol extract[66, 107]
CucurbitaceaeMomordica foetida Schumach.ShootWater0.35 (chloroquine resistant, FCR3); 6.16 (chloroquine sensitive, NF54)Saponins, alkaloid, phenolic glycosides including 5,7,4′-Trihydroxyflavanone and kaempferolNo pronounced toxicity against human hepatocellular (HepG2) and human urinary bladder carcinoma (ECV-304, derivative of T-24) cells[26, 28, 108]
EuphorbiaceaeAlchornea cordifolia (Schumach.) Mull. Arg.LeavesWater4.8 (chloroquine resistant, K1)Phenolics including ellagic acidNo mortality in mice in acute toxicity test[70, 109]
Fluegea virosa (Roxb. ExWillb.)VoigtLeavesWater/methanol2 (chloroquine resistant, W2)BergeninNontoxic, extracts exposed to murine macrophages did not slow or inhibit growth of cells[72, 110]
Phyllanthus (pseudo) niruri Mull. Arg.WaterRanged from 2.9 to 4.1 (both chloroquine sensitive, 3D7 and resistant, Dd2)Coumarins including 1-O-galloyl-6-O-luteoyl-a-D-glucoseNo toxicity was observed; thus, LD50 of the aqueous extract is >5000 mg/kg. b.w.[74, 111]
LamiaceaeClerodendrum rotundifolium Oliv.LeavesMethanol0.02 (chloroquine sensitive, CQS); 1.56 (chloroquine resistant, CQR)Iridoid glycosides such as serratoside A, serratoside B and monomelittoside, diterpenoids including uncinatone, clerodin, and sugiolNot explored[28, 33]
MimosaceaeAlbizia zygia (DC.) Macbr.Stem barkMethanol1.0 (chloroquine resistant, K1)Flavonoids, mainly 3′,4′,7-trihydroxyflavoneThe aqueous extract is relatively safe on subacute exposure[87, 112]
RubiaceaePentas longiflora Oliv.RootMethanol0.99 (chloroquine sensitive, D6); 0.93 (chloroquine resistant, W2)Pyranonaphthoquinones, pentalongin (1) and psychorubrin (2), naphthalene derivative mollugin (3)Low cytotoxicity[97]
RutaceaeCitrus reticulataSeeds (isolimonexic acid methyl ether)<4.76 (both chloroquine sensitive, D6 and resistant, W2)Limonin, isolimonexic acid methyl ether, ichangin, deacetylnomilin, obacunoneDermal 50% lethal dose (LD50) of undiluted leaf oil is >2 g/kg in rabbits; seed extract causes respiratory distress and strong spleen contraction[34, 113]

Although herbs are generally considered safer when used for treatment compared to conventional drugs, some of the herbs used traditionally to treat malaria in Uganda may be efficacious, but there is a need to have them used with caution as some may be toxic (Table 4). There is a variation in degree of toxicity depending on the sensitivity of animals, tissue or cells used, type of extract, nature of the test substance, dose, and mode of administration [114]. According to Lacroix et al. [32] one third of the herbs for malaria treatment in Uganda they investigated had significant antiplasmodial activity with low toxicity. Some of the plant parts with good antiplasmodial/antimalarial activities with no or low toxicity include leaves of A. annua, leaves of A. africana, S. pinnata whole plant, leaves of C. papaya, and leaves of F. virosa amongst others (Table 4). There are however extracts of some plants used for malaria treatment with very good activity against Plasmodium but with high toxicity; such plant extracts include petroleum ether leaf extract of V. amygdalina and dichloromethane leaf extract of M. pyrifolia (Table 4) [32, 55]. Clerodendrum rotundifolium is on those plants that have very good antimalarial/antiplasmodial activities but have not been investigated for their toxicity (Table 4) [33].

8. Traditional Health Care Practice and Policy Framework in Uganda

The health care system of Uganda consists of the public, private-profit oriented, and private-nonprofit oriented sectors. There is quite a large sector of informal health care including traditional medicine practitioners, drug shops, medicine vendors, and complementary and alternative practitioners. The contribution of traditional health practitioners to Uganda’s health care system was not valued until lately [115]. The negative perspective could be traced back to the colonial times when culture including use of traditional medicine such as herbs for treatment was considered primitive and so discouraged [115]. Efforts are now being made to promote the use of traditional medicine since the government has realized that traditional health practitioners are key contributors to its primary health care system [115]. The Ministry of Health created a public-private partnership with the traditional health practitioners following a recommendation that they be brought into the mainstream health system [115, 116].

A policy on Traditional and Complementary Medicine was created to regulate traditional medicine practice focusing on research and development while emphasizing the propagation, protection, and sustainable use of medicinal plant resources [115, 116]. For collaboration between the mainstream health care sector and traditional health practitioners, the Ministry of Health submitted a bill for the creation of the National Council of Indigenous and Complementary Medicine Practitioners, a semiautonomous body that shall as well protect their intellectual property rights [115, 116].

The National Drug Authority (NDA) is a body that ensures quality control of all medical products including herbal medicines in Uganda under the government statute and policy of 1993 [117]. In Uganda, there is no special regulatory measure for herbal medicines in that the same laws and policies for conventional pharmaceuticals also apply to the herbal medicinal products. A policy was introduced in 2002 to have herbal medicines registered, but so far, no registration of any herbal medicine has been made [117].

Herbal medicines though vastly used in Uganda are not sufficiently regulated. A system to license and track traditional health practitioners or their products is still lacking in the country, and the efforts to have the TCM integrated in the mainstream health care system is still a long way from being realized.

9. Conclusion

Uganda is rich in indigenous plant resources that are used by its people to treat malaria. Communities in different regions of the country use different herbs within their geographical range, though a few common herbs are used by different communities across the country. Many herbs used for malaria treatment among several communities have not been investigated for their efficacy, and yet they could be potential sources for antimalarial remedies including drugs. Few studies have been conducted to document herbs for malaria treatment in the country, especially in the northern region. Some of the plants investigated for antimalarial/antiplasmodial activities have been found to lack efficacy, toxicity, and safety study aspects. Some plants used in the local communities had very strong antimalarial activities and could be investigated further for the identification and validation of the potential therapeutic antimalarial compounds. This review is critical in that it clearly highlights herbal plants documented in Uganda for malaria treatment but have never been investigated for their antimalarial potential, thus providing guidance for further research on potential natural plant resources that could be sources of novel compounds with therapeutic properties for the treatment of malaria.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Authors’ Contributions

Denis Okello carried out the data search and was the main contributor in writing the manuscript. Youngmin Kang technically designed and helped in writing the manuscript. Both authors read and approved the final manuscript.

Acknowledgments

This study was supported under the framework of International Cooperation Program (Korea-South Africa Cooperative Research Project for Excavation of Candidate Resources of Complementary and Alternative Medicine) managed by National Research Foundation of Korea (grant nos. 2017093655 and KIOM:D17470). Additionally, this study was equally supported by grants from Development of Foundational Techniques for the Domestic Production of Herbal Medicines (K18405) and Applicational Development of Standardized Herbal Resources (KSN1911420), from the Korea Institute of Oriental Medicine (KIOM), through the Ministry of Science and ICT, Republic of Korea.

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