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

Authors: Denis Okello; Youngmin Kang
Journal: Evidence-Based Complementary and Alternative Medicine
 (2019)

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## 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.


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## Body

## 1. Introduction

Malaria, a dangerous and life-threatening disease caused byPlasmodium 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].Figure 1
Illustration of some common symptoms of malaria.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.Figure 2
Malaria prevalence in Uganda (modified from [12]).


## 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 (Table1) [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].Table 1
Herbs used in the treatment of malaria in Uganda.
Plant family
Scientific name
Local name
Part used
Growth form
Mode of preparation
Dose and mode of administration for malaria
Status of antimalarial/antiplasmodial activity investigation
Other ailments treated
Reference(s)
Acanthaceae
Justicia betonica L.
Nalongo/quinine
Leaves/whole plant
Herb
Decoction
About 120 ml every 8 hours for a week
Investigated
Diabetes, yellow fever, diarrhea
[10, 19]
Justicia anselliana (Nees) T. Anderson
Kwiniini omuganda
Leaves/twig
Herb
Decoction
Orally taken, dose not specified
No record
[20]
Monechma subsessile C. B. Clarke
Erazi
Leaves
Decoction
Orally taken, dose not specified
No record
Abdominal pain
[19]
Thunbergia alata Sims
Kasaamusaamu/ntudde buleku
Leaves/whole plant
Climber
Decoction
About 120 ml every 8 hours for a week
No record
False teeth
[8, 10]
Alliaceae
Allium cepa L.
Katungulu
Bulb
Herb
No record
[21]
Aloeaceae
Aloe dawei A. Berger (wild/cultivated)
Kigagi
Leaves
Herb
Decoction
A glassful once a day for 7 days
Investigated
Candida
[10]
Aloe kedongensis (wild)
Kigagi
Leaves
Herb
Decoction
Orally taken, dose not specified
Investigated
[19, 22]
Aloe volkensii (cultivated)
Kigagi
Leaves
Herb
Decoction/infusion
Orally taken, dose not specified
No record
[19]
Aloe ferox Mill
Kigagi
Leaves
Herb
Decoction
Orally taken, dose not specified
Investigated
Wounds, digestive disorders, rheumatic arthritis
[18, 19]
Aloe lateritia (wild)
Kigagi
Leaves/root
Herb
Decoction
Orally taken, dose not specified
No record
[19]
Amaranthaceae
Amaranthus hybridus L.
Bbuga
Leaves
Herb
Decoction
Half a glass every 24 hours for 7 days
No record
[10]
Anacardiaceae
Mangifera indica L.
Muyembe gwakona
Leaves/bark
Tree
Decoction
4 and 3 teaspoons after every 8 hours for adults and children, respectively, for a week
Investigated
Diarrhea, dysentery, body pain, venereal diseases, cough, syphilis
[10, 23]
Rhus natalensis Bernh. Ex Krauss
Omesheshe
Leaves
Shrub
Decoction
Orally taken, dose not specified
Investigated
[24]
Rhus vulgaris Meikle
Kakwasokwaso/tebudda
Leaves
Shrub
Decoction
Half a glass every 8 hours for 7 days
No record
Skin rush, erectile dysfunction
[10]
Apiaceae
Heteromorpha trifoliata Eckl. & Zeyh.
Omumemena
Leaves/roots
Herb
Decoction
Orally taken, dose not specified
No record
[19]
Centella asiatica (L.) Urb.
Kabo Kabakyala/mbutamu
Leaves/whole plant
Herb
Decoction
4 teaspoons thrice a day for 4 days
Investigated
[10]
Apocynaceae
Alstonia boonei De Wild.
Mubajangalabi
Bark
Tree
Decoction
Orally taken, dose not specified
Investigated
[8]
Carissa edulis (Forssk.) Vahl
Muyunza, ekamuriei
Roots
Herb
Decoction
Orally taken, dose not specified
Investigated
Epilepsy, fever, cough, syphilis, measles, dysentery
[21, 23]
Carissa spinarum Lodd. ex A. DC.
Omuyonza
Roots
Decoction
Orally taken, dose not specified
Investigated
[19]
Catharanthus roseus G. Don
Sekagya
Leaves
Herb
Decoction
About 120 ml every 8 hours for a week
Investigated
[10]
Araceae
Culcasia faleifolia Engl.
Ntangawuzi yomukibira
Roots
Herb
Decoction
About 120 ml once a day for a week
No record
[10]
Aristolochiaceae
Aristolochia elegans Mast.
Musuja welaba/nakasero
Seeds/sap
Vine
Steeped in water and drunk
A glassful once a day
Investigated
Abdominal pain, East coast fever
[8, 19]
Aristolochia tomentosa Sims.
Kankapu
Stem
Climber
Infusion
Oral, dose not specified
No record
Wounds, skin diseases, snake bites
[23]
Asclepiadaceae
Gomphocarpus physocarpus E. Mey.
Kafumbo
Leaves
Herb
Decoction
Half a glass daily for a week
No record
[10]
Asphodelaceae
Aloe vera (L.) Burm. f.
Kigagi/alovera
Leaves
Herb
Decoction
1 teaspoon and 1 tablespoon 3 times a day for children and adults, respectively, for a week
Investigated
Stomach ache
[8, 25]
Asteraceae
Ageratum conyzoides L.
Namirembe
Whole plant/leaves
Herb
Decoction
A glassful thrice a day for 7 days
Investigated
Worms, weakness in pregnancy
[8, 10]
Artemisia annua L.
Sweet anne
Leaves
Herb
Decoction
Oral, dose not specified
Investigated
Fever
[19]
Artemisia afra Jacq. ex Willd
Pasile
Leaves
Herb
Infusion
Oral, dose not specified
Investigated
Fever
[10]
Aspilia africana (Pers.) C. D. Adams
Makayi, ekarwe
Whole plant/leaves/roots
Herb
Decoction
8 teaspoons 3 times a day for a week
Investigated
Abdominal aches, measles, diarrhea, wounds, induction of appetite
[10, 19]
Baccharoides adoensis (Sch. Bip. ex Walp.) H. Rob.
Okellokello
Leaves
Shrub
Decoction
1 teaspoon and 1 tablespoon 3 times a day for children and adults, respectively, for a week; bath-leaves squeezed and added to bathing water
Investigated
Flu, skin rush, ear infections
[25, 26]
Bidens grantii Sherff
Ehongwa
Leaves, flower
Herb
Decoction
Oral, dose not specified
No record
Pregnancy disorders, prehepatic jaundice
[19]
Bidens pilosa L.
Sere/labika
Whole plant/leaves
Herb
Decoction/fresh leaf extract
4 teaspoons thrice a day for 4 days
Investigated
Diarrhea, wounds
[10, 23]
Bothriocline longipes N. E. Br.
Ekyogayanja
Leaves
Decoction
Oral, dose not specified
Investigated
Fever, ague, paludism
[19, 24]
Conyza bonariensis (L.)
Ndasha
Leaves
Decoction
Oral, dose not specified
No record
Stomach ache, body pain, anemia, respiratory problems
[19]
Conyza floribunda H. B. K.
Kafumbe
Leaves
Herb
Decoction
About 120 ml once a day for a week
No record
Headache
[10]
Conyza sumatrensis (Retz.) E. H. Walker
Kati kati
Leaves
Herb
No record
Wounds, sore throat, ringworms
[21, 27]
Crassocephalum vitellinum
Kitonto
Leaves
Herb
Honey added to decoction
2 teaspoons thrice a day for 7 days
Investigated
[10, 19]
Emilia javanica (Burm. F.) C. B. Rob.
Nakate
Whole plant
Herb
Decoction
Half a glass once a day for a week
No record
[10]
Guizotia scabra Chiov.
Ekiterankuba
Leaves
Decoction
Oral, dose not specified
Investigated
Stomach ache, HIV/AIDS opportunistic infections
[19]
Gynura scandens O. Hoffm.
Ekizimya-muriro
Leaves
Decoction
Oral, dose not specified
No record
Febrile convulsions
[19]
Melanthera scandens (Schumach. & Thonn.) Roberty
Makaayi
Leaves
Herb
Decoction
Oral, dose not specified
Investigated
Stomach ache, body odour, yellow fever
[8]
Pluchea ovalis DC.
Omuneera
Leaves
Decoction
Oral, dose not specified
No record
[19]
Microglossa pyrifolia (Lam.)O. Ktze
Kafugankande
Whole plant/leaves/roots
Herb
Decoction
Half a glass thrice a day for a week
Investigated
Cough, abdominal disorders, chest pain
[10, 19, 28]
Schkuhria pinnata (Lam.)
Apunait
Leaves
Herb
Infusion
1 teaspoon and 1 tablespoon 3 times a day for children and adults, respectively, for a week
Investigated
Wounds, skin diseases, diabetes, ear infections, wounds
[23, 25]
Sigesbeckia orientalis L.
Kyaryaho
Roots
Decoction
Oral, dose not specified
No record
Wounds, stomach ache
[19]
Solanecio mannii (Hook. f.) C. Jeffrey
Omusununu
Leaves
Decoction
Oral, dose not specified
Investigated
Fever, indigestion
[19]
Sonchus oleraceus L.
Entahutara
Leaves
Decoction
Oral, dose not specified
No record
Stomach ache, scars, anemia, diarrhea
[8, 19]
Tagetes minuta L.
Kawunyira
Whole plant/leaves
Herb
Decoction
Half a glass thrice a day for a week
Investigated
Flu, headache, convulsions
[10]
Tithonia diversifolia A. Gray
Kimyula
Leaves
Herb
Decoction
Half a glass thrice a day for a week
Investigated
Diabetes, abdominal pain
[10, 19, 25]
Vernonia adoensis Sch. Bip. ex Walp.
Nyakajuma
Leaves/flowers
Decoction
Oral, dose not specified
Investigated
Diarrhea, dizziness
[19]
Vernonia amygdalina Delile
Mululuza/labwori
Whole plant/roots
Shrub
Decoction
Half a glass 2 times a day for 5 days
Investigated
Headache, stomach ache, burns, baths
[8, 10, 19, 20]
Vernonia cinerea (L.) Less.
Kayayana
Bark
Tree
Decoction
Half a glass thrice a day for a week
Investigated
Fever, vomiting, inflammation
[10]
Vernonia lasiopus O. Hoffm.
Kaluluza kasajja
Roots/leaves
Shrub
Fresh leaf extract/root decoction
2 teaspoons thrice a day for 7 days
Investigated
Abdominal pain, cough, migraine headache, delayed delivery
[8, 10, 19, 20]
Bignoniaceae
Markhamia lutea (Benth.) K. Schum.
Musambya/muzanganda
Roots
Tree
Decoction
A glassful once a day for 7 days
Investigated
Cough, diarrhea
[8, 10, 19]
Spathodea campanulata Buch. -Harm. ex DC.
Kifabakazi
Bark
Tree
Decoction
Half a glass 3 times a day for 5 days
Investigated
Increased vaginal fluid, skin infection, infertility, hernia
[8, 10]
Caesalpiniaceae
Cassia didymobotrya Fres.
Mukyula
Leaves
Shrub
Decoction
About 120 ml every 8 hours for a week
Investigated
[10]
Chamaecrista nigricans Greene
Epeduru lo didi
Leaves
Herb
Infusion
Oral, dose not specified
No record
Labour induction, hypertension, retained placenta
[23]
Erythrophleum pyrifolia
Omurama
Leaves/roots
Investigated
[24]
Senna spectabilis (DC.) H. S. Irwin & Barneby
Gasiya
Leaves
Tree
Decoction
Half a glass twice a day for 5 days
Investigated
[10]
Caesalpinioideae
Cassia hirsuta
Kasagalansansi
Roots
Herb
Infusion
Investigated
Stomach pains
[23]
Canelliaceae
Warbugia ugandensis Sprague
Omukuzanume
Bark/leaves
Tree
Decoction/powder swallowed with banana
Half a glass once a day for a week
Investigated
Toothache, flu, skin diseases, asthma, stomach ache, body and muscle pain
[10, 20, 27]
Caricaceae
Carica papaya L.
Paapali essajja
Leaves
Tree
Decoction
Half a glass twice a day for 3 days
Investigated
Snake bite, sterility, cough, cancer, body pain, induces labour
[10, 19, 23, 25]
Celastraceae
Maytenus senegalensis
Echomai
Roots
Tree
Decoction
Oral, dose not specified
Investigated
Toothache, skin diseases, chest pain, wound, fever
[23]
Chenopodiaceae
Chenopodium ambrosioides L.
Kawuna wuna
Leaves
Investigated
Headache, epilepsy
[21]
Chenopodium opulifolium Koch & Ziz
Namuvu
Leaves
No record
Oral wounds, skin rush, toothache
[8, 21]
Combretaceae
Combretum molle G. Don
Ndagi
Bark
Tree
Decoction
Half a glass once a day for 3 days
Investigated
Cough,
[10, 21]
Crassulaceae
Kalanchoë densiflora Rolfe
Kisanasana
Leaves
Herb
No record
[21]
Cucurbitaceae
Cucurbita maxima Lam.
Kasuunsa
Leaves
Herb
Decoction
Half a glass once a day for 7 days
Investigated
Abdominal pain
[10, 25, 27]
Momordica foetida Schumach.
Orwihura
Leaves
Decoction
Oral, dose not specified
Investigated
Vomiting, baths, cough, flue, worms
[19, 26, 28]
Dracaenaceae
Dracaena steudneri Engl.
Kajjolyenjovu
Leaves
Herb
Decoction
Half a glass thrice a day for a week
No record
Scars, cough, syphilis, kidney stones, snake bites
[8, 10]
Ebenaceae
Euclea latideus Staff
Emusi
Roots
Shrub
Decoction
Oral, dose not specified
Investigated
Ringworms, swollen legs
[23]
Euphorbiaceae
Alchornea cordifolia (Schumach.) Mull. Arg.
Luzibaziba
Leaves
Herb
Decoction
Half a glass once a day for 7 days
Investigated
Shaking body
[8, 10]
Bridelia micrantha Baill.
Katazamiti
Bark
Tree
Decoction
Half a glass thrice a day for a week
Investigated
[10]
Clutia abyssinica Jaub. & Spach
Omubarama
Leaves
Decoction
Oral, dose not specified
Investigated
Fever, diarrhea
[19]
Croton macrostachyus Olive.
Ookota
Roots/bark
Tree
Decoction
Oral, dose not specified
Investigated
Tuberculosis, stomach ache, cough, fever, asthma
[23]
Fluegea virosa (Roxb. ExWillb.)Voigt
Lukandwa/mukandula
Leaves
Shrub
Decoction
Half a glass 3 times a day for a week
Investigated
Miscarriage, chest pains, infertility in women
[8, 10, 21, 23]
Jatropha curcas L.
Kirowa
Leaves
Shrub
Investigated
Tooth decay, headache, weakness in pregnancy
[21]
Macaranga schweinfurthii Pax
Kyeganza
Bark
Tree
Decoction
Half a glass 3 times a day for a 5 days
No record
[10]
Phyllanthus (pseudo) niruri Mull. Arg.
Nakitembe
Leaves
Shrub
Decoction
Half a glass 3 times a day for a 7 days
Investigated
[10]
Shirakiopsis elliptica (Hochst.) H.–J. Esser
Musasa
Back
Tree
Decoction
Oral, dose not specified
No record
[20]
Tetrorchidium didymostemon (Baill.) Pax & K. Hoffm.
Ekiziranfu
Bark
Decoction
Used as enema
No record
Jaundice, measles, gastrointestinal disorders, enema
[8, 19]
Fabaceae
Arachis hypogea (NC)
Ebinyobwa
Leaves
Fresh extract
Oral, dose not specified
No record
[19]
Cajanus cajan (L.) Druse
Entondaigwa
Leaves
Shrub
Fresh extract
100 ml once a day for a week
Investigated
Diarrhea, body pain
[27]
Crotalaria agatiflora Schweinf.
Kijjebejebbe
Whole shoot
Shrub
Fresh extract
Daily bath
No record
High blood pressure
[10]
Crotalaria ochroleuca G. Don
Alayo
Leaves
Herb
Fresh extract
1 teaspoon and 1 tablespoon 3 times a day for children and adults, respectively, for a week
No record
Stomach ache
[28]
Entada abyssinica Steud. ex A. Rich.
Mwolola
Leaves
Tree
Decoction
Investigated
Oral wounds, body weakness, wounds, skin infections
[8, 20, 26]
Entada africana Guill. & Perr.
Mwolola
Bark
Tree
Decoction
4 and 3 teaspoons after every 8 hours for adults and children, respectively, for a week
Investigated
[10]
Erythrina abyssinica Lam.
Girikiti/lacoro
Bark
Tree
Decoction
Half a glass 3 times a day for a 5 days
Investigated
Fever, leprosy, burns, tuberculosis, toothache, syphilis
[10, 23]
Erythrina excelsa Bak.
Bajjangala
Bark
Tree
Decoction
Half a glass 3 times a day for a week
No record
Wounds, candida
[10]
Indigofera arrecta Hochst. Ex A. Rich
Omushoroza
Roots/bark
No record
Abdominal pain
[19]
Indigofera congesta Baker
Namasumi
Twig
Herb
Infusion
Oral, dose not specified
No record
[8, 20]
Indigofera emerginella Steud. ex A. Rich
Omunyazabashumba
Leaves/roots
Shrub
Decoction
Oral, dose not specified
Investigated
Cough
[19]
Macrotyloma axillare Verdc.
Akihabukuru
Leaves
No record
Impotence, dizziness
[19]
Pseudarthria hookeri Wight & Arn
Omukongorani/kikakala
Leaves/whole plant
Herb
Decoction
One teaspoon thrice a day for 4 days
No record
Fever
[19, 20, 25, 29]
Rhynchosia viscosa DC
Omutegansi
Flower
No record
Labour induction
[19]
Senna absus (L.) Roxb.
Mucuula
Shrub
Leaves
Fresh extract
Oral, dose not specified
No record
Prolonged embryo in uterus
[8]
Senna didymobotrya (Fresen.) H. S. Irwin & Barneby
Omugabagaba/kivumuzi
Herb
Leaves, twig
Decoction
Oral, dose not specified
Investigated
Change of sex of child
[8, 19, 20, 29]
Senna siamea (Lam.) H. S. Irwin & Barneby
Garcia
Roots
Tree
Fresh extract
A cupful (500 ml) once a day for 3 days
Investigated
Abdominal pain, sore throat
[25, 27]
Tamarindus indica L.
Cwaa/nkoge
Bark
Tree
Decoction
Oral, dose not specified
Investigated
Convulsions, fever
[8, 21]
Flacourtiaceae
Ocoba spinosa Forssk
Ekalepulepu
Roots
Herb
Decoction
Oral, dose not specified
No record
Syphilis, skin problems, wounds, headache, impotence, stomach ache
[23]
Trimeria bakeri Gilg.
Omwatanshare
Leaves
Shrub
Decoction
Oral, dose not specified
Investigated
[24]
Hypericaceae
Harungana madagascariensis Lam.
Mukaabiransiko/mulirira
Bark
Tree
Decoction
2 tablespoons thrice a day for 3 days
Investigated
Yellow fever
[8, 10]
Labiatae
Hyptis pectinata Poir.
Bongoloza
Whole plant
Herb
Decoction
Oral, dose not specified
No record
[20, 29]
Lamiaceae
Aeolanthus repens Oliv.
Ntulagi
Leaves
Herb
Decoction
Quarter a glass thrice a day for 3 days
No record
[10]
Ajuga remota Benth.
Kitinwa
Leaves
Herb
Decoction
Half a glass once a day for a week
Investigated
Stomach ache
[10]
Clerodendrum myricoides R. Br.
Kikonge
Leaves
Shrub
Decoction
Half a glass daily for a week
Investigated
Syphilis, intestinal problems, induction of labour
[10, 28]
Clerodendrum rotundifolium Oliv.
Kisekeseke
Roots/leaves
Shrub
Fresh leaf extract/root decoction
Half a glass daily for a 5 days
Investigated
Diabetes
[10]
Hoslundia opposita Vahl.
Kamunye
Leaves
Herb
Decoction
Half a glass 3 times a day for a week; bath
Investigated
Ulcers
[8, 10, 25]
Leonotis nepetifolia Schimp. exBenth
Kifumufumu
Whole plant
Herb
Decoction
A glassful thrice a day for 3 days
Investigated
Headache
[10, 21]
Ocimum basilicum
Emopim
Leaves
Herb
Infusion
Half a glass 3 times a day for a week
Investigated
Fever, eye cataract
[23, 27]
Ocimum gratissimum Willd.
Mujaaja
Leaves
Herb
Decoction
Half a glass 3 times a day for 5 days
Investigated
Wounds, ear infections, chest pain
[10, 21]
Ocimum lamiifolium Hochst.
Omwenyi
Leaves
Decoction
Half a glass 3 times a day for a week
Investigated
Abdominal pain
[19]
Plectranthus barbatus
Ebiriri omutano
Whole plant/leaves, roots/stem
Herb
Infusion
Oral, dose not specified
Investigated
Fever, heart disease, snake bite
[10, 23]
Plectranthus caninus Roth
Kibwankulata
Leaves
Herb
Decoction
4 and 2 teaspoons thrice a day for adults and children, respectively, for a week
No record
[10]
Plectranthus cf. forskohlii
Ekizera
Leaves
Decoction
Oral, dose not specified
No record
[19]
Rosmarinus officinalis L.
Rosemary
Leaves
Herb
Decoction
Half a glass twice a day for 5 days
Investigated
Chest pain
[10]
Tetradenia riparia (Hochst.) Codd
Kyewamala
Leaves
Herb
Decoction
One teaspoon twice a day for a week
Investigated
[10]
Lauranceae
Persea americana Mill.
Ovakedo
Leaves
Tree
Decoction
Oral, dose not specified
Investigated
Fungal and bacterial infection, high blood pressure, intestinal worms and parasites
[23]
Loranthaceae
Tapinanthus constrictiflorus (Engl.) Danser
Enzirugaze
Leaves
Herb
Decoction
A glass daily for 7 days
No record
[10]
Malvaceae
Hibiscus surattensis L.
Nantayitwako musota
Leaves
Shrub
Decoction
Half a glass thrice a day for 7 days
No record
High blood pressure
[10]
Meliaceae
Azadirachta indica A. Juss.
Neem
Leaves
Tree
Decoction
About 120 ml once a day for 7 days
Investigated
Dental decay/ache, yellow fever, cough, skin diseases, diabetes, nausea
[10, 19, 23, 25]
Carapa grandiflora Sprague
Omukeete
Leaves/bark
Tree
Decoction
Half a glass twice a day for 7 days
No record
[10]
Melia azedarach
Elira
Leaves
Tree
Decoction
Oral, dose not specified
Investigated
Fever, skin disease, itching wounds, parasitic worms
[23]
Menispermaceae
Cissampelos mucronata A. Rich.
Kavawala
Leaves/whole plant
Herb
Decoction
Half a glass twice a day for 5 days
Investigated
[10]
Mimosaceae
Acacia hockii De willd
Ekisim
Roots
Tree
Decoction
Oral, dose not specified
No record
Diarrhea, syphilis, dysentery
[23, 30]
Acacia nilotica
Investigated
[31]
Acacia sieberiana
Etiriri
Roots
Tree
Decoction
Oral, dose not specified
No record
Dysentery, epilepsy, cough
[21, 23]
Albizia coriaria Welw.
Lugavu
Bark
Tree
Decoction
1 and 3 teaspoons thrice a day for children and adults, respectively, for a week.
Investigated
Skin diseases, diarrhea
[10]
Albizia grandibracteata Taube
Nongo
Bark
Tree
Decoction
Half a glass once a day for a week
Investigated
Yellow fever, anemia, fungal infections of scalp
[8, 10, 32]
Albizia zygia (DC.) Macbr.
Mulongo
Bark
Tree
Investigated
[21]
Newtonia buchananii (Baker) Gilb. & Perr.
Mpewere
Bark
Tree
Dried, powdered, added to boiling water
Half a glass once a day for a week
No record
[10]
Moraceae
Antiaris toxicaria Lesch.
Kirundu
Bark
Tree
Decoction
Half a glass once a day for a week
Investigated
Weakness in pregnancy, headache
[8, 10]
Ficus natalensis Hochst
Tree
Investigated
Gonorrhea
[8, 33]
Ficus saussureana DC.
Muwo
Bark
Tree
Decoction
Half a glass thrice a day for 7 days
No record
[10]
Milicia excels (Welw.) C. C. Berg.
Mivule
Bark
Tree
Decoction
Half a glass thrice a day for 7 days
Investigated
Burns, fresh cuts, skin rush
[8, 10]
Moringaceae
Moringa oleifera Lam
Moringa
Leaves/roots
Tree
Decoction/chewed raw
A glassful thrice a day for 7 days; a handful of fresh leaves chewed 3 times for 4 days
Investigated
Joint pains
[21, 25]
Musaceae
Musa paradisiaca (NC)
Kabalagala
Leaves
Herb
Decoction
Oral, dose not specified
Investigated
Jaundice, prolonged embryo in uterus
[19]
Myricaceae
Myrica kandtiana Engl. (NC)
Omujeeje
Leaves
Decoction
Oral, dose not specified
No record
Vomiting, diarrhea
[19]
Myristicaceae
Pycnanthus angolensis (Welw.)Warb.
Lunaba
Leaves
Tree
Decoction
Half a glass a day
Investigated
[10]
Myrsinaceae
Maesa lanceolata Forssk.
Kiwondowondo
Leaves
Shrub
Decoction
Half a glass thrice a day for 7 days
Investigated
Febrile convulsions
[10, 19, 24]
Myrtaceae
Eucalyptus grandis Maiden.
Kalitunsi
Leaves
Tree
Decoction
Half a glass a day
No record
Cough
[8, 10]
Psidium guajava L.
Mupeera
Leaves
Tree
Decoction
Half a glass thrice a day for a week
Investigated
Bloody diarrhea, typhoid, wounds, cough
[10, 23]
Syzygium cordatum Hochst.
Mugeege
Bark
Tree
Decoction
Oral, dose not specified
Investigated
Dry cough, skin rush, wounds
[8, 10, 20, 29]
Syzygium cumini (L.) Skeels
Jambula
Leaves
Tree
Decoction
Half a glass thrice a day for a week
Investigated
Cough
[32]
Syzygium guineense (Willd.) DC.
Kalunginsanvu
Bark
Tree
Decoction
Oral, dose not specified
Investigated
[20]
Papillionaceae
Butyrospermuum paradoxum
Ekunguri
Roots
Tree
Decoction
Oral, dose not specified
No record
Labour pains, headaches
[23]
Ormocarpum trachycarpum
Ederut
Roots
Shrub
Decoction
Oral, dose not specified
No record
Pneumonia, snake bite
[23]
Passifloraceae
Passiflora edulis Sims
Akatunda
Leaves
Herb
Fresh extract
Oral, dose not specified
No record
Diarrhea, cough
[19]
Pittosporaceae
Pittosporum brachcalya
Not defined
Not defined
Shrub
No record
[34]
Pittosporum mannii Hook. f. Subsp. ripicola (J. Leon)Cuf.
Mubajjankon
Leaves
Shrub
Infusion/decoction
Half a glass a day for a week
No record
[10]
Poaceae
Cymbopogon citratus Stapf.
Kisubi
Leaves
Grass
Decoction
120 ml every after 8 hours for a week
Investigated
Dental caries, influenza, cough, cancer, indigestion, fever
[10, 19, 23]
Digitaria scalarum Chiov.
Lumbugu
Leaves
Grass
Decoction
120 ml every after 8 hours for a week
No record
[10]
Imperata cylindrical (L.) Beauv. var. africana (Anderss.) C. E. Hubbard
Lusenke
Roots
Grass
Dried, powdered, added boiling water/decoction
120 ml once a day for a week
No record
Abdominal pain
[10]
Zea mays L.
Luyange lwakasoli
Flowers/husks
Cereal grass
Decoction
120 ml every after 8 hours for a week
Investigated
Boosts immunity
[10]
Polygalaceae
Securidaca longipedunculata Fresen.
Eliloi
Roots
Shrub
Decoction
Oral, dose not specified
Investigated
Skin diseases, measles, cough, hernia, diarrhea
[23]
Maesopsis eminii Engl.
Musizi
Bark
Tree
Decoction
Half a glass thrice a day for a week
No record
[10]
Portulacaceae
Talinum portulacifolium (Forssk.) Asch. ex Schweinf.
Mpozia
Leaves
Herb
Oral, dose not specified
No record
[21]
Rosaceae
Prunus africana (Hook. f.) Kalkman
Ntaseesa or Ngwabuzito
Bark
Tree
Decoction
2 and 3 teaspoons thrice a day for children and adults, respectively, for a week
Investigated
Fainting, cancer
[8, 10]
Rubus steudneri schweinf.
Nkenene
Leaves
Herb
Decoction
Half a glass once a day for a week
No record
[10]
Rubiaceae
Coffea canephora Froehner
Mwanyi
Leaves
Shrub
Decoction
Oral, dose not specified
No record
[21]
Hallea rubrostipulata (K. Schum.) J.-F. Leroy
Muziku
Bark
Tree
Decoction
Oral, dose not specified
Investigated
[20]
Pentas longiflora Oliv.
Ishagara
Leaves
Decoction
Oral, dose not specified
Investigated
Fever
[19]
Vangueria apiculata K. Schum.
Matugunda
Bark
Shrub
Decoction
2 and 3 teaspoons thrice a day for children and adults, respectively, for a week
No record
[10]
Rutaceae
Citrus reticulata
Omuqugwa
Roots
Tree
Decoction
Oral, dose not specified
Investigated
Weight loss induction, cancer, skin diseases
[23]
Citrus sinensis
Omucungwa/cungwa
Roots
Tree
Decoction
Oral, dose not specified
Investigated
Vomiting, cough, diabetes
[21, 23, 25]
Teclea nobilis Delile
Omuzo
Aerial parts
Decoction
Oral, dose not specified
Investigated
Body cleanser
[32]
Toddalia asiatica Baill.
Kawule
Roots
Climber
Decoction
Half a glass thrice a day for a week
Investigated
Cough, abdominal pain
[10, 19, 24]
Zanthoxylum chalybeum Engl.
Ntale ya ddungu
Roots
Tree
Decoction
Oral, dose not specified
Investigated
Body swellings, stomach ache, cough, fever, chest pain
[10, 23, 28]
Zanthoxyllum leprieurii Guill. & Perr.
Mutatembwa/munyenye
Bark
Tree
Decoction drunk
Half a glass thrice a day for a week
No record
[10]
Salicaceae
Trimeria grandifolia ssp. tropica (Hochst.) Warb.
Omwatanshare
Leaves
Decoction
Oral, dose not specified
Investigated
[19]
Sapindaceae
Blighia unijugata Baker
Nkuzanyana
Bark
Tree
Decoction drunk
Half a glass twice a day for a week
Investigated
Wounds, vomiting, skin diseases, fibroids, cervical cancer
[8, 10]
Sapotaceae
Manilkara obovata (Sabine & G. Don)
Nkunya
Bark
Tree
Decoction
Oral, dose not specified
No record
[20]
Scrophulariaceae
Sopubia ramosa (Hochst.) Hochst.
Kakulunkanyi
Whole plant
Herb
Decoction
Oral, dose not specified
No record
[20]
Simaroubaceae
Harrisonia abyssinica Olive.
Ekeroi
Roots/leaves
Shrub
Decoction
Oral, dose not specified
Investigated
Fever, wounds, syphilis, snake bite, abdominal pain
[23]
Solanaceae
Datura stramonium Thunb.
Amadudu
Leaves
Herb
Decoction drunk
Half a glass thrice a day for a week
No record
Ulcers, stomach ache, chest pain
[10]
Physalis peruviana L.
Ntuntunu
Leaves
Herb
Decoction drunk
Half a glass 3 times a day for a week
No record
Vomiting, febrile convulsions, fainting
[8, 10, 19]
Solanum nigrum L.
Nsugga
Leaves
Herb
Decoction drunk
Half a glass 3 times a day for a week
Investigated
Ear infection, headache, epilepsy, STI, diarrhea
[8, 10]
Tiliaceae
Trumfetta rhomboidea Jacq.
Musombankoko
Roots
Shrub
Decoction drunk
Half a glass once a day for a week
No record
[10]
Ulmaceae
Celtis africana L.
Akasisa
Leaves
Tree
Decoction drunk
Half a glass a day for a week
Investigated
[10]
Umbelliferae
Steganotania araliacea Hoeshst
Ematule
Roots/leaves
Tree
Decoction
Oral, dose not specified
No record
Measles, body swelling
[23]
Verbenaceae
Lantana camara
Kanpanga
Leaves
Shrub
Decoction
Oral, dose not specified
Investigated
Wounds, measles, tuberculosis, pneumonia, snake bite, chest pain
[23]
Lantana trifolia L.
Omuhukye
Leaves
Decoction
Orally taken, dose not specified
Investigated
Yellow fever, ringworms, muscle pain, prolapsed rectum
[8, 19]
Zingiberaceae
Curcuma longa L.
Binjali
Rhizome
Herb
Fresh extract
30 ml thrice a day for 3 days
Investigated
[28]Table 2
Some herbs used in malaria prevention amongst communities in Uganda.
Plant family
Plant species
Local name
Plant form
Mode of use to prevent malaria
Reference(s)
Cleomaceae
Cleome gynandra L.
Akeyo
Herb
Leaves are cooked and eaten as a prophylactic measure
[25]
Cucurbitaceae
Cucurbita maxima Duchesne
Acuga
Scrambler
Leaves cooked and pasted with groundnut then eaten
[25]
Euphorbiaceae
Manihot esculenta Crantz
Gwana
Herb
Tuber peelings are dried then burnt in house so that smoke repels mosquitoes
[25]
Fabaceae
Crotalaria ochroleuca G. Don
Alayo
Herb
Leaves are cooked and eaten as a prophylactic measure
[25]
Lamiaceae
Ocimum forsskaolii Benth.
Yat cola
Herb
Leaves dried and burnt so that smoke chases away mosquitoes; bath infusion to repel mosquito
[25]
Rosmarinus officinalis L.
Rosemary
Herb
Leaves are cooked and eaten as a prophylactic measure; planted around the house to repel mosquitoes
[10]
Malvaceae
Gossypium hirsutum L.
Pama
Shrub
Cotton lint is dried and burnt so that smoke keeps away mosquitoes
[25]
Musaceae
Musa sp.
Labolo kwon
Shrub
Fruit peeling are dried and burnt in the house to produce smoke that keeps away mosquitoes
[25]
Myrtaceae
Eucalptus grandis Maiden.
Kalitunsi
Tree
Leave and branches are burnt to repel mosquitoes
[25]
Poaceae
Cymbopogon citratus Stapf.
Kisubi
Grass
Planted around the house to repel mosquitoes; taken in tea as a prophylactic measure
[19, 23]
Solanaceae
Solanum americanum Mill.
Ocuga
Herb
Leaves 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 (Table3). 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].Table 3
Antiplasmodial/antimalarial activities of investigated plants used for malaria treatment in Uganda and their active chemical constituents.
Plant family
Scientific name
Part used
Extracting solvent
Means of traditional extraction
Report on antiplasmodial, IC50 (μg/ml)/antimalarial activity (Plasmodium strain)
Active chemical constituents
Reference(s)
Acanthaceae
Justicia betonica L.
Shoot
Methanol
Hot water
69.6 (chloroquine sensitive, K39)
Justetonin (indole(3,2-b) quinoline alkaloid glycoside)
[20]
Water
>100 (chloroquine sensitive, K39)
Aloeaceae
Aloe dawei A. Berger (wild/cultivated)
Leaves
Ether
Cold water; mashing; hot water
Extract 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)
Leaves
Methanol
Hot water
87.7 (chloroquine sensitive, D6); 67.8 (chloroquine resistant, W2)
Anthrone, C-glucoside homonataloin, anthraquinones, aloin, lectins
[19, 46]
Aloe ferox Mill
Leaves
Dichloromethane
Water
21 (chloroquine sensitive, D10)
Mannans, polymannans, anthraquinones, aloin, lectins, anthrones
[19, 31, 47]
Water
>100 (chloroquine sensitive, D10)
Anacardiaceae
Mangifera indica L.
Leaves
Chloroform:Methanol (1 : 1)
Hot water
Inhibited growth ofP. falciparum by 50.4% at 20 μg/ml
Phenolics
[48, 49]
Stem bark
Ethanol
>50 (chloroquine resistant, FcB1)
Rhus natalensis Bernh. Ex Krauss
Leaves
Ethanol
Hot water
6.6 (P. falciparum)
Triterpenoids
[24]
Apiaceae
Centella asiatica (L.) Urb.
Whole plant
Water
Water
58.6 (chloroquine sensitive, D6); not detected (chloroquine resistant, W2)
Phenolics and flavonoids
[50]
Apocynaceae
Alstonia boonei De Wild.
Stem bark
Water
Hot water
80.97% suppressive activity at 200 mg/kg (P. berghei) in combination with other two local herbs.
Alkaloids, triterpenoids
[51]
Carissa edulis (Forssk.) Vahl
Stem bark
Dichloromethane
Mashing; hot water
33 (chloroquine sensitive, D10)
Lignan, nortrachelogenin
[52]
Carissa spinarum Lodd. ex A. DC.
Root bark
Methanol
Hot water
14.5 (chloroquine sensitive, D6)
Saponins, sesquiterpenes
[53]
Catharanthus roseus G. Don
Leaves
Methanol
Hot water
4.6 (chloroquine sensitive, D6); 5.3 (chloroquine resistant, W2)
Alkaloids, terpenoids, flavonoids, esquiterpenes
[54]
Aristolochiaceae
Aristolochia elegans Mast.
Seeds
Methanol
Water
>50 (chloroquine sensitive, 3D7); undetectable (chloroquine resistant, W2)
Sesquiterpenoids, diterpenoids, monoterpenoids, alkaloids
[19, 55]
Asphodelaceae
Aloe vera (L.) Burm. f.
Leaves
Water
Cold water; mashing; hot water
Antiplasmodial activity in terms of EC50 values 0.289 to 1.056 μg/ml (chloroquine sensitive)
Aloin, anthraquinones, aloe-emodin
[56]
Asteraceae
Ageratum conyzoides L.
Whole plant
Methanol
Hot water
11.5 (chloroquine sensitive, D6); 12.1 (chloroquine resistant, W2)
Flavonoids
[54]
Artemisia annua L.
Leaves
Water
Hot water
1.1 (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 Willd
Leaves
Methanol
Hot water
9.1 (chloroquine sensitive, D6); 3.9 (chloroquine resistant, W2)
Acacetin, genkwanin, 7-methoxyacacetin
[54]
Aspilia africana (Pers.) C. D. Adams
Leaves
Ethanol
Hot water
Significant chemo suppressive effect of 92.23% (400 mg/kg) onP. berghei
Saponins, terpenoids, alkaloids, resins, tannins, flavonoids, sterols
[19, 58]
Baccharoides adoensis (Sch. Bip. ex Walp.) H. Rob.
Leaves
Petroleum ether
Hot water
4.6 (chloroquine resistant, K1)
Flavonoids
[26]
Aspilia africana L.
Leaves
Dichloromethane
Hot water; mashing
8.5 (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.
Leaves
Chloroform
Hot water
3.7 (P. falciparum)
5-alkylcoumarins,
[19, 24]
Ethanol
50 (P. falciparum)
Crassocephalum vitellinum
Leaves
Ethyl acetate
Hot water
40.6% inhibition ofP. falciparum at 10 μg/ml
Flavonoids
[32]
Guizotia scabra Chiov.
Whole plant
Crude ethanol
Hot water
49.09% growth inhibition at 100 μg/ml (chloroquine resistant, Dd2)
Lactones, eudesmanoline
[59]
Melanthera scandens (Schumach. & Thonn.) Roberty
Leaves
Chloroform
Hot water
68.83% chemo suppression activity (P. berghei)
Triterpenoid saponins
[60]
Microglossa pyrifolia (Lam.)O. Ktze
Leaves
Hot water
<5 (both chloroquine sensitive, NF54 and resistant, FCR3)
E-phytol; 6e-geranylgeraniol-19-oic acid
[2, 28]
Schkuhria pinnata (lam.)
Whole plant
Water
Hot water
22.5 (chloroquine sensitive, D6); 51.8 (chloroquine resistant, W2)
Schkuhrin I and schkuhrin II
[54]
Methanol
1.3 (chloroquine sensitive, D6); 6.8 (chloroquine resistant, W2)
Solanecio mannii (Hook. f.) C. Jeffrey
Leaves
Methanol
Water
21.6 (chloroquine sensitive, 3D7); 26.2 (chloroquine resistant, W2)
Phytosterols, n-alkanes and N-hexacosanol,
[19, 55]
Tagetes minuta L.
Leaves
Ethyl acetate
Water
61.0% inhibition ofP. falciparum at 10 μg/ml
[32]
Tithonia diversifolia A. Gray
Leaves
Methanol
Water
1.2 (chloroquine sensitive, 3D7); 1.5 (chloroquine resistant, W2)
Tagitinin C, sesquiterpene lactones
[55]
Vernonia adoensis Sch. Bip. ex Walp.
Leaves
Methanol
Hot water
83.4% inhibition of parasitaemia, at 600 mg/kg (P. berghei)
Glycocides, glaucolides
[19, 61]
Vernonia amygdalina Delile
Leaves
Methanol/dichloromethane
Hot water; cold water
2.7 (chloroquine resistant, K1)
Coumarin, sesquiterpene lactones including vernolepin, vernolin, vernolide, vernodalin and hydroxyvernodalin, steroid glucosides
[19, 26]
Vernonia cinerea (L.) Less.
Whole plant
Water
Hot water
>50 (chloroquine sensitive, 3D7); 37.2 (chloroquine resistant, K1)
Sesquiterpene lactone
[62]
Vernonia lasiopus O. Hoffm.
Leaves
Methanol
Mashing; hot water
44.3 (chloroquine sensitive, D6); 52.4 (chloroquine resistant, W2)
Sesquiterpene lactones, polysaccarides
[19, 54]
Bignoniaceae
Markhamia lutea (Benth.) K. Schum.
Leaves
Ethyl acetate
Hot water
71% inhibition ofP. falciparum at 10 μg/ml
Phenylpropanoid glycosides, cycloartane triterpenoids
[32]
Spathodea campanulata Buch.-Harm. ex DC.
Stem bark
Ethyl acetate
Water
28.9% inhibition ofP. falciparum at 10 μg/ml
Quinone (lapachol)
[32]
Caesalpiniaceae
Cassia didymobotrya Fres.
Leaves
Methanol
Hot water
23.4 (chloroquine sensitive, D6); undetectable (chloroquine resistant, W2)
Alkaloids
[54]
Erythrophleum pyrifolia
Leaves
Ethanol
Hot water
>50 (P. falciparum)
[24]
Senna spectabilis (DC.) H. S. Irwin & Barneby
Leaves
Ethanol
Water
59.29% growth inhibition at 100 mg/kg body weight dose(P. berghei)
Piperidine alkaloids
[63]
Caesalpinioideae
Cassia hirsuta
Root back
Methanol
Water
32.0 (chloroquine sensitive 3D7)
[64]
Canelliaceae
Warbugia ugandensis Sprague
Stem back
Methanol
Hot water
6.4 (chloroquine sensitive, D6); 6.9 (chloroquine resistant, W2)
Sesquiterpenes e.g. muzigadiolide
[27, 54]
Water
12.9 (chloroquine sensitive, D6); 15.6 (chloroquine resistant, W2)
Caricaceae
Carica papaya L.
Leaves
Ethyl acetate
Hot water
2.96 (chloroquine sensitive, D10); 3.98 (chloroquine resistant, DD2)
Alkaloids, saponins, tannins, glycosides
[65]
Methanol
10.8 (chloroquine sensitive, D10)
Celastraceae
Maytenus senegalensis
Roots
Hot water
1.9 (chloroquine sensitive, D6); 2.4 (chloroquine resistant, W2)
Terpenoids, pentacyclic triterpenes e.g. pristimerin
[66]
Chenopodiaceae
Chenopodium ambrosioides L.
Leaves
Crude hydroalcoholic extract
Hot water
Inhibited theP. falciparum growth, exhibiting an IC50 of 25.4 μg/ml
Sesquiterpenes, monoterpenes
[67]
Combretaceae
Combretum molle G. Don
Stem back
Acetone
Water
8.2 (chloroquine sensitive 3D7)
Phenolics, punicalagin
[68]
Cucurbitaceae
Cucurbita maxima Lam.
Seeds
Crude ethanol
Hot water
50% reduction of parasitaemia levels inP. berghei infected mice at 500 mg/kg.
Phenols, terpenoids, alkaloids, tannins
[69]
Momordica foetida Schumach.
Shoot
Water
Hot water
6.16 (chloroquine sensitive, NF54); 0.35 (chloroquine resistant, FCR3)
Saponins, alkaloid, cardiac glycosides
[28]
Ebenaceae
Euclea latideus Staff
Root back
Hexane
Water
38.2 (chloroquine sensitive, 3D7); 38.9 (chloroquine resistant, Dd2)
Triterpenoids lupeol, betulin, 3β-(5-hydroxyferuloyl)lup-20(30)-ene
[23]
Euphorbiaceae
Alchornea cordifolia (Schumach.) Mull. Arg.
Leaves
Water
Hot water
4.8 (chloroquine resistant, K1)
Phenolics including ellagic acid
[70]
Bridelia micrantha Baill.
Stem bark
Methanol
Hot water
19.4 (chloroquine sensitive, D6); 14.2 (chloroquine resistant, W2)
[50]
Clutia abyssinica Jaub. & Spach
Leaves
Methanol
Water
7.8 (chloroquine sensitive, D6); 11.3 (chloroquine resistant, W2)
Diterpenes
[54]
Croton macrostachyus Olive.
Leaves
Chloroform
Hot water
Chemotherapeutic effect of 66–82% in malaria mouse model
Triterpenoids including lupeol
[71]
Fluegea virosa (Roxb. ExWillb.)Voigt
Leaves
Water/methanol
Hot water
2 (chloroquine resistant, W2)
Bergenin
[72]
Jatropha curcas L.
Leaves
Ethyl acetate
Hot water
5.1 (chloroquine sensitive, NF54); 2.4 (chloroquine resistant, K1)
Alkaloids, saponnins, glycosides, tannins
[73]
Phyllanthus (pseudo) niruri Mull. Arg.
Water
Hot water
Ranged 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]
Fabaceae
Cajanus cajan (L.) Druse
Leaves
Crude ethanol
Mashing
29.0 (P. falciparum)
Cajachalcone;
[75]
Entada abyssinica Steud. ex A. Rich.
Seeds
Methanol
Hot water
>5 (chloroquine resistant, K1)
Flavonoids, terpenoids
[26, 32]
Entada africana Guill. & Perr.
Leaves
Ethanol
Hot water
26.4 (chloroquine sensitive, HB3); 28.9 (chloroquine resistant, FcM29)
Phenolics
[76]
Erythrina abyssinica Lam.
Stem bark
Ethyl acetate
Hot water
83.6% inhibition ofP. falciparum at 10 μg/ml
Chalcones (5-prenylbutein, homobutein), flavanones including 5-deoxyabyssinin II, abyssinin III and abyssinone IV
[32]
Indigofera emerginella Steud. ex A. Rich
Leaves
Ethanol
Hot water
5.8 (P. falciparum)
[24]
Senna didymobotrya (Fresen.) H. S. Irwin & Barneby
Leaves
Methanol
Hot water
>100 (chloroquine sensitive, K39)
Quinones
[20, 29]
Senna siamea (Lam.) H. S. Irwin & Barneby
Leaves
Ethanol
Mashing; hot water
28.8 (chloroquine sensitive, 3D7); 48.3 (chloroquine resistant, W2)
Phenolic derivative, chrobisiamone a, anhydrobarakol
[77]
Tamarindus indica L.
Stem bark
Water
Hot water
25.1% chemo suppressive activity at 10 mg/kg (P. berghei)
Saponins (leaves), tannins (fruits)
[78]
Flacourtiaceae
Trimeria bakeri Gilg.
Leaves
Petroleum ether
Hot water
3.9 (P. falciparum)
Triterpenoids
[24]
Hypericaceae
Harungana madagascariensis Lam.
Stem bark
Water
Hot water
9.64 (chloroquine resistant, K1)
Quinones including bazouanthrone, feruginin a, harunganin, harunganol a
[70]
Lamiaceae
Ajuga remota Benth.
Whole plant
Ethanol
Hot water
55 (chloroquine sensitive, FCA/GHA); 57 (chloroquine resistant, W2)
Ajugarin-1, ergosterol-5,8-endoperoxide, 8-O-acetylharpagide, steroids
[79]
Clerodendrum myricoides R. Br.
Root bark
Methanol
Hot water
4.7 (chloroquine sensitive, D6); 8.3 (chloroquine resistant, W2)
[50, 80]
Clerodendrum rotundifolium Oliv.
Leaves
Methanol
Mashing; hot water
<5 (both chloroquine sensitive, NF54 and resistant, FCR3)
Saponins, tannins
[28]
Hoslundia opposita Vahl.
Leaves
Ethyl acetate
Hot water
66.2% inhibition ofP. falciparum at 10 μg/ml
Quinones, saponins, abietane diterpenes (3-O-benzoylhosloppone)
[32]
Leonotis nepetifolia Schimp. exBenth
Leaves
Ethyl acetate
Water
27.0% inhibition ofP. falciparum at 10 μg/ml
[32]
Ocimum basilicum
Leaves
Ethanol
Hot water
68.14 (chloroquine sensitive, CQ-s); 67.27 (chloroquine resistant, CQ-r)
[50, 80]
Ocimum gratissimum Willd.
Leaves/twigs
Dichloromethane
Hot water
8.6 (chloroquine resistant, W2)
Flavonoids
[47, 49]
Ocimum lamiifolium Hochst.
Leaves
Water
Water
Significantly suppressed parasitaemia, 22.2%, 26.8% and 35.5% at dose of 200, 400 and 600 mg·kg, respectively (P. berghei)
[81]
Plectranthus barbatus
Leaves/stem
Dichloromethane
Hot water
No activity
[23, 47]
Rosmarinus officinalis L.
Hot water
Essential oil at a concentration 15867 ng/ml had no antimalarial activity
[82]
Tetradenia riparia (Hochst.) Codd
Root
Hot water
13.2 (chloroquine-sensitive, NF54)
[83]
Lauranceae
Persea americana Mill.
Leaves
Ethanol
Hot water
10.15 (chloroquine sensitive, 3D7); 44.94 (chloroquine resistant, W2)
Phenolics
[84]
Meliaceae
Azadirachta indica A. Juss.
Leaves
Hot water
17.9 (chloroquine sensitive, D6); 43.7 (chloroquine resistant, W2)
Terpenoids, isoprenoids, gedunin
[49, 66]
Melia azedarach
Leaves
Methanol
Hot water
55.1 (chloroquine sensitive, 3D7); 19.1 (chloroquine resistant, W2)
[85]
Menispermaceae
Cissampelos mucronata A. Rich.
Root bark
Methanol
Hot water
8.8 (chloroquine sensitive, D6); 9.2 (chloroquine resistant, W2)
Benzylisoquinoline alkaloids
[80]
Mimosaceae
Acacia nilotica
Stem bark
Methanol
Hot water
Dose of 100 mg/kg b/w produced parasitic (P. berghei) inhibition 77.7%
Tannins, flavonoids, terpenes
[86]
Albizia coriaria Welw.
Stem bark
Methanol
Hot water
15.2 (chloroquine sensitive, D6); 16.8 (chloroquine resistant, W2)
Triterpenoids, lupeol, lupenone
[54]
Albizia grandibracteata Taube
Leaves
Ethyl acetate
Hot water
22.0% inhibition ofP. falciparum at 10 μg/ml
[32]
Albizia zygia (DC.) Macbr.
Stem bark
Methanol
Water
1.0 (chloroquine resistant, K1)
Flavonoids mainly 3′,4′,7-trihydroxyflavone
[87]
Moraceae
Antiaris toxicaria Lesch.
Stem bark
Ethyl acetate
Hot water
36.4% inhibition ofP. falciparum at 10 μg/ml
[32]
Ficus natalensis Hochst
Leaves
Hexane
Hot water
6.7 (P. falciparum)
[88]
Milicia excels (Welw.) C. C. Berg.
Leaves
Ethanol
Hot water
76.7% chemo suppressive activity at 250 mg/kg/day (P. berghei)
[89]
Moringaceae
Moringa oleifera Lam
Leaves
Methanol
Mashing; hot water
9.8 (chloroquine sensitive, D6); not detected (chloroquine resistant, W2)
Flavonols
[49, 80]
Musaceae
Musa paradisiaca (NC)
Leaves
Ethyl acetate
Hot water
75 (chloroquine sensitive, 3D7); 100 (chloroquine resistant, Dd2)
Flavonoids
[49, 90]
Myristicaceae
Pycnanthus angolensis (Welw.)Warb.
Leaves
50% ethanol
Hot water
>1000 (chloroquine sensitive, 3D7)
Talaumidin
[91]
Myrsinaceae
Maesa lanceolata Forssk.
Twig
Dichloromethane:Methanol (1 : 1)
Hot water
5.9 (chloroquine sensitive, D10)
Lanciaquinones, 2,5, dihydroxy-3-(nonadec-14-enyl)-1,4-benzoquinone
[24, 52, 55]
Myrtaceae
Psidium guajava L.
Stem back
Water
Hot water
10–20 (chloroquine sensitive, D10)
Phenols, flavonoids, carotenoids, terpenoids
[49, 92]
Syzygium cordatum Hochst.
Twig
Dichloromethane:Methanol (1 : 1)
Hot water
14.7 (chloroquine sensitive, D10)
[55]
Syzygium cumini (L.) Skeels
Stem back
Hot water
0.25 to 27.1 (chloroquine-resistant strains)
[93]
Syzygium guineense (Willd.) DC.
Leaves
Crude ethanol
Hot water
49.09% chemo suppression at 400 mg/kg (P. berghei)
[94]
Poaceae
Cymbopogon citratus Stapf.
Whole plant
Hot water
99.89% suppression of parasitaemia at 1600 mg/kg
Flavonoids
[20, 49, 95]
Zea mays L.
Husks
Ethyl acetate
Hot water
9.3 (chloroquine sensitive, 3D7); 3.7 (chloroquine resistant, INDO)
Alkaloids, flavonoids and triterpenoids
[96]
Polygalaceae
Securidaca longipedunculata Fresen.
Leaves
Dichloromethane
Hot water
6.9 (chloroquine sensitive, D10)
Saponins, flavonoids, alkaloids, steroids
[92]
Rosaceae
Prunus africana (Hook. f.) Kalkman
Stem bark
Methanol
Hot water
17.3 (chloroquine sensitive, D6); not detected (chloroquine resistant, W2)
Terpenoids
[54]
Rubiaceae
Hallea rubrostipulata (K. Schum.) J.-F. Leroy
Root
Ethanol
Water
100 μg/ml extract had 65.54% growth inhibition (chloroquine resistant, Dd2)
Alkaloids
[59]
Pentas longiflora Oliv.
Root
Methanol
Hot water
0.99 (chloroquine sensitive, D6); 0.93 (chloroquine resistant, W2)
Pyranonaphthoquinones, pentalongin (1) and psychorubrin (2), naphthalene derivative mollugin (3)
[97]
Rutaceae
Citrus reticulata
Seeds (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 sinensis
70% ethanol
Hot water
53.27% suppression of parasitaemia at 700 mg/kg
Tannins, alkaloids, saponins, flavonoids
[20, 24, 99]
Teclea nobilis Delile
Bark
Ethyl acetate
Water
54.7% inhibition ofP. falciparum at 10 μg/ml
Quinonline alkaloids
[32]
Toddalia asiatica Baill.
Root bark
Methanol
Water
6.8 (chloroquine sensitive, D6); 13.9 (chloroquine resistant, W2)
Furoquinolines (nitidine, 5,6-dihydronitidine), coumarins
[80]
Zanthoxylum chalybeum Engl.
Stem bark
Water
Hot water
4.3 (chloroquine sensitive, NF54); 25.1 (chloroquine resistant, FCR3)
Chelerythine, nitidine, methyl canadine
[28]
Salicaceae
Trimeria grandifolia ssp. tropica (Hochst.) Warb.
Leaves
Methanol
Hot water
>50 (chloroquine sensitive, 3D7)
[55]
Sapindaceae
Blighia unijugata Baker
Leaves
Ethyl acetate
Hot water
2.3% inhibition ofP. falciparum at 10 μg/ml
[32]
Simaroubaceae
Harrisonia abyssinica Olive.
Roots
Hot water
4.4 (chloroquine sensitive, D6); 10.25 (chloroquine resistant, W2)
Limonoids, steroids
[66]
Solanaceae
Solanum nigrum L.
Fruit
Methanol
Hot water
10.3 (chloroquine sensitive, 3D7); 18.7 (chloroquine resistant, K1)
Steroidal alkaloids, flavonoids
[100]
Ulmaceae
Celtis africana L.
Stem bark
Ethyl acetate
Hot water
37.5% inhibition ofP. falciparum at 10 μg/ml
[32]
Verbenaceae
Lantana camara
Leaves
Dichloromethane
Hot water
8.7 (chloroquine sensitive, 3D7); 5.7 (chloroquine resistant, W2)
Sesquiterpenes, triterpenes, flavonoids
[30]
Lantana trifolia L.
Arial parts
Petroleum ether
Hot water
13.2 (P. falciparum)
Steroids, terpenoids, alkaloids, saponins
[24]
Ethanol
>50 (P. falciparum)
Zingiberaceae
Curcuma longa L.
Hot water; mashing
5 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 asB. 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 inP. 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 (Table1). 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)).Figure 3
(a) Composition of plant species in each family used to treat malaria. (b) Percentage use of plant parts for treatment of malaria.
(a)
(b)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 (Figure3(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 ofM. 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 asB. 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, inA. 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 (IC50 <5 μg/ml in one of its solvent extracts or high percentage inhibition of plasmodia) that could be potentially investigated further.Table 4
Top 17 herbal plants used locally in Uganda for malaria treatment with highest antimalarial/antiplasmodial activities (arranged alphabetically).
Plant family
Plant species
Plant part
Extracting solvent
Report on antiplasmodial, IC50 (μg/ml)/antimalarial activity (Plasmodium strain)
Active chemical constituents
Toxicity/safety information
Reference(s)
Asteraceae
Artemisia afra Jacq. Ex Willd
Leaves
Methanol
3.9 (chloroquine resistant, W2)
Acacetin, genkwanin, 7-methoxyacacetin
Cytotoxicity was observed in Vero cells
[54, 103]
Artemisia annua L.
Leaves
Water
0.9 (chloroquine resistant, W2); 1.1 (chloroquine sensitive, D10)
Sesquiterpenes and sesquiterpene lactones including artemisinin
Generally 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. Adams
Leaves
Ethanol
Significant chemo suppressive effect of 92.23% (400 mg/kg) onP. berghei
Saponins, terpenoids, alkaloids, resins, tannins, flavonoids, sterols
No signs of toxicity in mice even at a dose as high as 5000 mg/kg
[19, 58]
Jatropha curcas L.
Leaves
Ethyl acetate
2.4 (chloroquine resistant, K1)
Alkaloids, saponnins, glycosides, tannins
Moderate 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. Ktze
Leaves
Dichloromethane
1.5 (chloroquine sensitive, 3D7; 2.4 chloroquin resistant, W2)
E-phytol; 6e-geranylgeraniol-19-oic acid
Relatively high cytotoxicity against cells from the human foetal lung fibroblast cell line
[2, 28, 55]
Schkuhria pinnata (lam.)
Whole plant
Methanol
1.3 (chloroquine sensitive, D6)
Schkuhrin I and schkuhrin II
Methanol extract: low cytotoxicity against human cells; aqueous extracts: no observed toxicity observed in mice
[32, 54]
Tithonia diversifolia A. Gray
Leaves
Methanol
1.2 (chloroquine sensitive, 3D7); 1.5 (chloroquine resistant, W2)
Tagitinin C, sesquiterpene lactones
Aerial parts are cytotoxic against cells from the human foetal lung fibroblast cell line
[55]
Vernonia amygdalina delile
Leaves
Methanol/dichloromethane
2.7 (chloroquine resistant, K1)
Coumarin, sesquiterpene lactones including vernolepin, vernolin, vernolide, vernodalin and hydroxyvernodalin, steroid glucosides
Petroleum ether extract shows strong cytotoxicity
[19, 26, 32]
Caricaceae
Carica papaya L.
Leaves
Ethyl acetate
2.96 (chloroquine sensitive, D10); 3.98 (chloroquine resistant, DD2)
Alkaloids, saponins, tannins, glycosides
No serious toxicity reported, carpaine, an active compound againstP. falciparum had high selectivity and was nontoxic to normal RBCs
[65, 106]
Celastraceae
Maytenus senegalensis
Roots
1.9 (chloroquine sensitive, D6); 2.4 (chloroquine resistant, W2)
Terpenoids, pentacyclic triterpenes, e.g., pristimerin
No toxicity observed in ethanol extract
[66, 107]
Cucurbitaceae
Momordica foetida Schumach.
Shoot
Water
0.35 (chloroquine resistant, FCR3); 6.16 (chloroquine sensitive, NF54)
Saponins, alkaloid, phenolic glycosides including 5,7,4′-Trihydroxyflavanone and kaempferol
No pronounced toxicity against human hepatocellular (HepG2) and human urinary bladder carcinoma (ECV-304, derivative of T-24) cells
[26, 28, 108]
Euphorbiaceae
Alchornea cordifolia (Schumach.) Mull. Arg.
Leaves
Water
4.8 (chloroquine resistant, K1)
Phenolics including ellagic acid
No mortality in mice in acute toxicity test
[70, 109]
Fluegea virosa (Roxb. ExWillb.)Voigt
Leaves
Water/methanol
2 (chloroquine resistant, W2)
Bergenin
Nontoxic, extracts exposed to murine macrophages did not slow or inhibit growth of cells
[72, 110]
Phyllanthus (pseudo) niruri Mull. Arg.
Water
Ranged from 2.9 to 4.1 (both chloroquine sensitive, 3D7 and resistant, Dd2)
Coumarins including 1-O-galloyl-6-O-luteoyl-a-D-glucose
No toxicity was observed; thus, LD50 of the aqueous extract is >5000 mg/kg. b.w.
[74, 111]
Lamiaceae
Clerodendrum rotundifolium Oliv.
Leaves
Methanol
0.02 (chloroquine sensitive, CQS); 1.56 (chloroquine resistant, CQR)
Iridoid glycosides such as serratoside A, serratoside B and monomelittoside, diterpenoids including uncinatone, clerodin, and sugiol
Not explored
[28, 33]
Mimosaceae
Albizia zygia (DC.) Macbr.
Stem bark
Methanol
1.0 (chloroquine resistant, K1)
Flavonoids, mainly 3′,4′,7-trihydroxyflavone
The aqueous extract is relatively safe on subacute exposure
[87, 112]
Rubiaceae
Pentas longiflora Oliv.
Root
Methanol
0.99 (chloroquine sensitive, D6); 0.93 (chloroquine resistant, W2)
Pyranonaphthoquinones, pentalongin (1) and psychorubrin (2), naphthalene derivative mollugin (3)
Low cytotoxicity
[97]
Rutaceae
Citrus reticulata
Seeds (isolimonexic acid methyl ether)
<4.76 (both chloroquine sensitive, D6 and resistant, W2)
Limonin, isolimonexic acid methyl ether, ichangin, deacetylnomilin, obacunone
Dermal 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 (Table4). 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.



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*Source: 3057180-2019-09-15.xml*