Medicinal plants used for treatment of malaria by indigenous communities of Tororo District, Eastern Uganda

Abstract

Background

Malaria remains the leading cause of death in sub-Saharan Africa. Although recent developments such as malaria vaccine trials inspire optimism, the search for novel antimalarial drugs is urgently needed to control the mounting resistance of Plasmodium species to the available therapies. The present study was conducted to document ethnobotanical knowledge on the plants used to treat symptoms of malaria in Tororo district, a malaria-endemic region of Eastern Uganda.

Methods

An ethnobotanical study was carried out between February 2020 and September 2020 in 12 randomly selected villages of Tororo district. In total, 151 respondents (21 herbalists and 130 non-herbalists) were selected using multistage random sampling method. Their awareness of malaria, treatment-seeking behaviour and herbal treatment practices were obtained using semi-structured questionnaires and focus group discussions. Data were analysed using descriptive statistics, paired comparison, preference ranking and informant consensus factor.

Results

A total of 45 plant species belonging to 26 families and 44 genera were used in the preparation of herbal medicines for management of malaria and its symptoms. The most frequently mentioned plant species were Vernonia amygdalina, Chamaecrista nigricans, Aloe nobilis, Warburgia ugandensis, Abrus precatorius, Kedrostis foetidissima, Senna occidentalis, Azadirachta indica and Mangifera indica. Leaves (67.3%) were the most used plant part while maceration (56%) was the major method of herbal remedy preparation. Oral route was the predominant mode of administration with inconsistencies in the posology prescribed.

Conclusion

This study showed that the identified medicinal plants in Tororo district, Uganda, are potential sources of new antimalarial drugs. This provides a basis for investigating the antimalarial efficacy, phytochemistry and toxicity of the unstudied species with high percentage use values to validate their use in the management of malaria.

Supplementary Information

The online version contains supplementary material available at 10.1186/s41182-023-00526-8.

Background

Malaria remains one of the diseases with the highest human morbidities and mortalities in the world [1]. It is one of the greatest obstacles to socio-economic development, especially in the developing countries where it is endemic [2, 3]. In 2019, there were 229 million global malaria cases with a case incidence of 57% [1]. The African continent accounted for 95% of all global malaria cases, with Uganda accounting for 5% of these. In the same year, the global malaria mortality rate stood at 10 persons per 100,000 at risk. In 2020, there was a marked increase in global malaria incidence with about 14 million more cases and 69,000 additional deaths compared to 2019. About two-thirds of the mortalities were attributed to disruptions in malaria services during the COVID-19 pandemic, particularly in countries of the WHO African Region [1].

In East Africa, malaria remains endemic in the Lake Victoria basin, with Anopheles gambiae and Anopheles funestus being the implicated vectors perpetuating it [4, 5]. Plasmodium falciparum and Plasmodium vivax are the two deadliest malarial parasites in sub-Saharan Africa. Currently, artemisinin-based combination therapies (ACT) are the treatment of choice for malaria [6–8]. They are available for free but are sometimes hard to access in Ugandan government health centres and hospitals [9]. Early diagnosis and prompt treatment of malaria should occur within 24 h of the onset of symptoms to decrease the risk of severe complications and onward transmission which occurs within a few hours for P. falciparum malaria [10, 11]. Unfortunately, there are delays in seeking care, obtaining a diagnosis and receiving appropriate treatment by Ugandans which is associated with fatal malaria. While tremendous progress has been made in the fight against malaria through the improvement of health system performance and increased public knowledge about the disease, increasing resistance to commonly used treatments (including ACT) is presenting new challenges to malaria control and eradication programmes [12, 13]. Therefore, malaria cases remain high in Uganda, despite the availability of ACT [14, 15]. Due to the high risk of morbidity and mortality, the Ugandan government spends a lot of money on procuring antimalarial drugs for its citizens.

In spite of the success achieved regarding universal health coverage, traditional and complementary medicines have not remained an integral component of the health care system of Uganda. Traditional medicine is culturally accepted, readily available, free or cheap and is perceived to be safe and efficacious. The evaluation of plant materials for new drugs is justified because many modern allopathic medicines including antimalarial drugs originated from plants [16]. For example, the two main groups (artemisinin and quinine derivatives) of modern antimalarial drugs contain lead compounds derived from Cinchona species and Artemisia annua plant extracts, respectively [17]. Uganda forms part of the East African botanical plate which is rich in medicinal plants. Communities in different regions of the country use different herbs within their geographical range, although a few common herbs are used by different communities across the country [18]. However, ethnobotanical documentation of the medicinal plants used to treat malaria is far from complete among various communities in the country. Therefore, this study aimed at generating information that will contribute to the development of efficacious and safe antimalarial drugs, by documenting and prioritizing plants used for treating malaria in Tororo district, Eastern Uganda.

Methods

Study area

This was an ethnobotanical survey conducted in Tororo district (0° 41′ 34.0008″ N and 34° 10′ 51.9960″ E), Eastern Uganda (Fig. 1). Tororo borders Bugiri district to the West, Butaleja district to the North, Busia district to the South, Republic of Kenya to the East and Mbale district to the North East. It has a population of about 597,500 people distributed as 51.2% females, and 48.8% males. The majority of the people (86%) live in the rural areas. The major economic activity in the area is subsistence farming. Tororo district is one of the malaria-endemic districts with an entomological infective rate of 591, making it one of the most malaria burdened districts in Uganda [19, 20]. Despite government efforts to increase access to health services from health facilities, residents of Tororo district still rely on traditional medicine for their primary health care. This is attributed to the high level of poverty in the district, long distances travelled to access free health services and prolonged drug stockouts [21, 22].

Fig. 1.

Map showing the location of the study area. Inset is the map of Uganda showing the location of Tororo district

Sample size and sampling procedures

A sample size of 245 respondents was calculated using the formula suggested by Krejcie and Morgan [23]. Due to COVID-19 restrictions and limited resources, we interviewed only 151 respondents (21 traditional medicine practitioners and 130 common people, i.e. local people who regularly use plants for medicinal purposes). These respondents were both females and male aged 18 years and above.

Study design, selection of study sites and participants

Field survey for this study was conducted from February 2020 to September 2020 using a cross-sectional study design. Three sub-counties of Tororo district (Fig. 1) namely Eastern division, Kirewa, and Paya were randomly selected. Two parishes were randomly selected from each division and eventually, two villages were considered. This gave a total of 12 villages. In each village, herbalists were purposively sampled based on their reputation in the community to treat symptoms of malaria. As the key informants, herbalists were identified using snow balling method based on the principle of saturation [24]. Using this method, once an herbalist was identified and interviewed, they were asked to refer the research team to another herbalist within their networks. The subsequent herbalist then referred us to the next herbalist in their networks until saturation was reached. From each village, 10–15 respondents were interviewed altogether. Experienced non-herbalists were randomly selected to participate in the study after obtaining their prior informed consent.

Ethnobotanical data collection

A pilot study was undertaken in February 2020 to introduce the study to the local area administration, seek their permission to conduct the study and pre-test the study tool. Data were collected from the respondents following guidelines of conducting research during the COVID-19 pandemic established by the Uganda National Council of Science and Technology [25]. Data were collected using a semi-structured questionnaire which was translated into Japadhola, the principal language spoken in Tororo district. The questionnaire included questions on the respondent’s biodata, knowledge on signs and symptoms of malaria, harvesting, preparation, administration and dosage of malaria herbal medicines (Additional file 1: S1). Questions on the existing knowledge, attitudes and practices related to malaria recognition, control and treatment in Tororo district were also included. Three focus group discussions were held with community members (one per sub-county) to complement the questionnaire survey. Plants mentioned by respondents were identified during guided field walks with the informants [26]. Voucher specimen of each plant species were prepared for correct botanical identification and deposited at the Makerere University Herbarium. Species nomenclature follows the flora for tropical East Africa and was verified using the Plants of the World Online (POWO) database (https://powo.science.kew.org).

Data analysis

Numerical data were entered into Microsoft Excel spread sheet, coded, and exported to SPSS software (version 26, SPSS Inc.) for analysis. Descriptive statistics such as percentages and frequencies were used to summarize ethnobotanical and respondents’ socio-demographic data. Further, ethnobotanical data were used to calculate informant consensus factor as well as perform paired comparison and preference ranking.

Informant consensus factor

To determine the homogeneity of the ethnobotanical information collected from the respondents, the Informant Consensus Factor (ICF) was computed using formula 1 [27]:

$$\mathrm{ICF}=\frac{\mathrm{Nur}-\mathrm{Nt}}{\mathrm{Nur}-1},$$ 1

where “$\mathrm{Nur}$” refers to the total number of use reports for each disease cluster and “$\mathrm{Nt}$” refers the total number of species in each use category. The ICF values range from 0 to 1. High ICF values (close to 1) are obtained when only a few plant species are reported to be used by a high proportion of informants to treat a particular disease and this implies that there is a well-defined mechanism in the community of sharing information between informants. Low ICF values (close to 0) are obtained when many plant species are reported to be used by a high proportion of informants to treat a particular disease and this implies that there is no well-defined mechanism in the community of sharing information between informants.

Preference ranking

Preference ranking was performed as reported by Martin [28]. When a variety of plant species are utilized to treat the same health problem, individuals prefer one over the other. Key informants were given the task of comparing the given medicinal plants based on their values, with the highest number (5) given to medicinal plants which they preferred to be the most effective in treating malaria and the lowest number (1) given to those plants that they preferred to be the least effective in treating malaria [29].

Paired comparison of medicinal plants

A paired comparison was made for five medicinal plants used to treat malaria in the study area. Ten reputable herbalists were requested to rank the species based on their efficiency in management of malaria as follows: 1 = least, 2 = good, 3 = very good and 4 = excellent [29].

Results

Sociodemographic characteristics

The respondents were distributed by gender with 41.1% females and 58.9% males. The majority of these (94%) were married. The major occupation was subsistence farming (61.6%), followed by casual labour for wages (22.5%). The respondents had a median age of 46.0 years, and a significant percentage (65%) had attained only primary education (Table 1).

Table 1.

Socio-demographic characteristics of respondents from Tororo district

Characteristics	Frequency	Percentage (%)
Sex
Female	62	41.1
Male	89	58.9
Age group
18–34	65	43.0
35–59	75	49.7
60+	11	7.3
Marital status
Not married	9	6.0
Married	142	94.0
Religion
Catholic	45	29.6
Anglican	44	29.0
Moslem	32	21.5
Pentecostal	25	16.7
None	5	3.2
Ethnicity
Japadhola	101	67.0
Itesot	32	21.0
Other	18	12.0
Highest level of education
No formal education	3	2.0
Primary	98	65.0
Secondary	47	31.0
Tertiary university	3	2.0
Occupation
Casual workers for wages	34	22.5
Formal employment/professional	12	7.9
Subsistence farmer	93	61.6
Unemployed	12	7.9
Source of traditional knowledge
Parents and relatives	105	69.5
Other community members	44	29.1
Traditional medicine association	2	1.4

Knowledge on malaria, its symptoms and treatment-seeking behaviour of patients

Malaria appeared to be prevalent and well understood by the respondents in Tororo district. Most respondents (90%) had suffered from malaria in the last six months before the date of the interview. The respondents also mentioned the correct signs and symptoms of malaria (Fig. 2). Fever (33%) was the main sign of malaria reported by the respondents, followed by vomiting (13%) and body weakness (11%). Other signs and symptoms of malaria reported were headache (13%), diarrhoea (7%), convulsions (6%), loss of appetite (6%) and body chills (11%).

Fig. 2.

Reported signs and symptoms of malaria by respondents in Tororo district, Eastern Uganda

On developing malaria, most respondents (76%) reported that they used traditional medicine (TM) alone as the first line of treatment compared to 17.2% who used modern medicine (MM) alone. When they failed to improve, they switched to MM. Thus, on re-treatment, the number of people that used TM alone decreased to 51%, while 41% used MM (Fig. 3). In clinical practice, a first-line treatment/first-line therapy is the treatment that is accepted as best for the initial treatment of a condition or disease. In the context of our study, malaria patients tend to use herbal remedies (TM) as the first treatment for malaria before attempting to use MM. In case it fails, the second treatment sought after is MM.

Fig. 3.

Treatment options used by malaria patients in the studied communities of Tororo district, Eastern Uganda. TM: traditional medicine; MM: modern medicine

Plant species used in preparation of herbal remedies for malaria treatment in Tororo district

Forty-five plant species were mentioned by respondents in this study to be used in preparation of herbal remedies for management of symptoms of malaria (Table 2). Of the inventoried species, nine were mentioned by six or more people. These are; Vernonia amygdalina Delile (58), Chamaecrista nigricans (Vahl.) Greene (14), Aloe nobilis (L.) Burman. (13), Warburgia ugandensis Sprague (12), Abrus precatorius L. (11), Kedrostis foetidissima Cogn. (10), Senna occidentalis L., Azadirachta indica (7 each), and Mangifera indica L. (6). The species were distributed as trees (37.7%), shrubs (26.7%) and herbs (35.6%) by growth habit. These species were from 26 families and 44 genera. Fabaceae (17.8%), Asteraceae (8.9%), Lamiaceae and Rutaceae (6.7% each) were the most represented families (Fig. 4). The ICF for malaria calculated was 0.76, implying that there is considerable agreement among the community members in the medicinal plants used in management of malaria. For preference ranking, Vernonia amygdalina Delile, Chamaecrista nigricans (Vahl.) Greene and Aloe nobilis (L.) Burman. were ranked first, second and third, respectively (Table 3). The results of paired comparison test for the five frequently mentioned plant species, respondents (10) selected Vernonia amygdalina Delile first, followed by Chamaecrista nigricans (Vahl.) Greene, Warburgia ugandensis Sprague, Aloe nobilis (L.) Burman. and Abrus precatorius L. (Table 4).

Table 2.

Medicinal plants used in Eastern Division, Kirewa, and Paya sub-counties of Tororo district, Uganda, for treating malaria (n = 45)

S/N	Name	Local name	Family	Voucher no.	Habit	Part(s) used	Administration method	Frequency
1	Vernonia amygdalina Delile	Muluswa	Asteraceae	AN01	Shrub	Leaves	Oral	58
2	Chamaecrista nigricans (Vahl.) Greene	Achwa	Fabaceae	AN02	Herb	Leaves	Oral	14
3	Aloe nobilis (L.) Burman	Atworo	Asphodelaceae	AN03	Herb	Leaves	Oral	13
4	Warburgia ugandensis Sprague	Atiko	Canellaceae	AN04	Tree	Leaves	Oral	12
5	Abrus precatorius L	Osito	Fabaceae	AN05	Herb	Leaves	Oral	11
6	Kedrostis foetidissima Cogn	Nyamikesi	Cucurbitaceae	AN06	Herb	Root bark	Oral	10
7	Senna occidentalis L	Yeke yeke	Fabaceae	AN07	Shrub	Leaves	Oral	7
8	Azadirachta indica A. Juss	Arubaine	Meliaceae	AN08	Tree	Leaves	Oral	7
9	Mangifera indica L	Mayembe	Anacardiaceae	AN09	Tree	Leaves	Oral	6
10	Clerodendrum myricoides (Hochst.) Vatke	Okwero	Verbenaceae	AN10	Shrub	Stem, fruits, roots, leaves	Oral	3
11	Carissa spinarum L	Ochwoga	Apocynaceae	AN11	Shrub	Roots	Oral	3
12	Bidens pilosa L	Sere	Asteraceae	AN12	Herb	Leaves	Topical bath	3
13	Citrus limon (L.) Burm	Nimoo	Rutaceae	AN13	Tree	Leaves, roots	Steam bath	3
14	Eucalyptus camaldulensis Denhn	Kalitusi	Myrtaceae	AN14	Tree	Leaves	Topical bath	3
15	Tamarindus indica L	Chwa	Fabaceae	AN15	Tree	Leaves, stem	Oral	2
16	Psidium guajava L	Mapeera	Myrtaceae	AN16	Shrub	Leaves	Oral	2
17	Persea americana Mill	Avocado	Lauraceae	AN17	Tree	Leaves	Oral	2
18	Momordica foetida K. Schum	Woyo	Cucurbitaceae	AN18	Herb	Leaves	Oral	1
19	Clematis hirsuta Perr. & Guill	Adwe	Ranunculaceae	AN19	Herb	Leaves	Oral	1
20	Fagaropsis angolensis (Engl.) Dale	Rokoo	Rutaceae	AN20	Tree	Roots, leaves, fruits, seeds	Oral	1
21	Microglossa densiflora Hook.f	Omeryidiegi	Asteraceae	AN21	Herb	Root bark	Oral	1
22	Solanum ptychanthum Dunal	Ochoki	Solanaceae	AN22	Shrub	Fruits	Oral	1
23	Leonotis nepetifolia (L.) R.Br	Odhudho/Othutho	Lamiaceae	AN23	Herb	Leaves	Oral	1
24	Cannabis sativa L	Misaala	Cannabaceae	AN24	Herb	Leaves	Topical bath	1
25	Cissampelos mucronata A. Rich	Masu	Menispermaceae	AN25	Herb	Roots, leaves	Oral	1
26	Tetradenia riparia (Hochst.) Codd	Aboke	Lamiaceae	AN26	Shrub	Leaves	Oral	1
27	Oldenlandia herbacea (L.) Roxb	Alwari	Rubiaceae	AN27	Herb	Roots	Oral	1
28	Melia azedarach L	Lira	Meliaceae	AN28	Tree	Leaves, roots	Oral	1
29	Albizia coriaria Welw. ex Oliv	Oberi	Fabaceae	AN29	Tree	Stem	Oral	1
30	Ocimum basilicum L	Yathi ajwoka	Lamiaceae	AN30	Herb	Leaves	Topical bath	1
31	Toddalia asiatica (L.) Lam	Thwolikiluwi	Rutaceae	AN31	Shrub	Leaves	Oral	1
32	Harrisonia abyssinica Oliv	Pedo	Simaroubaceae	AN32	Shrub	Fruits	Oral	1
33	Acacia campylacantha Hochst.ex A. Rich	Mugogwe	Fabaceae	AN33	Tree	Root bark	Oral	1
34	Urena lobata L	Mbirambira	Malvaceae	AN34	Shrub	Leaves	Oral	1
35	Annona senegalensis Pers	Obolo	Annonaceae	AN35	Tree	Root wood	Oral	1
36	Vitex doniana Sweet	Yuelo/Uwelo	Verbenaceae	AN36	Tree	Leaves, roots	Oral	1
37	Ficus cyathistipula Warb	Bongi	Moraceae	AN37	Tree	Leaves	Oral	1
38	Carica papaya L	Mapapali	Caricaceae	AN38	Tree	Leaves	Oral	1
39	Vigna unguiculata (L.) Walp	Boo	Fabaceae	AN39	Herb	Leaves	Oral	1
40	Panicum maximum Jacq	Thiwi odunyo	Poaceae	AN40	Herb	Leaves	Oral	1
41	Moringa oleifera Lam	Moringa	Moringaceae	AN41	Tree	Leaves, roots	Topical bath	1
42	Desmodium velutinum (Willd.) DC	Sirangende	Fabaceae	AN42	Herb	Root bark	Oral	1
43	Punica granatum L	Nkomamawanga	Lythraceae	AN43	Shrub	Leaves, roots	Oral	1
44	Vernonia adoensis Sch. Bip. ex Walp	Muluswa matari	Asteraceae	AN44	Shrub	Leaves	Oral	1
45	Grevillea robusta A. Cunn. ex R.Br	Grevillia	Proteaceae	AN45	Tree	Leaves	Oral	1

Fig. 4.

Distribution of medicinal plant species for management of malaria in Tororo district by families

Table 3.

Preference ranking of medicinal plants used for treating malaria in Tororo District, Eastern Uganda

Name of species	Respondents (R1–R7)							Score	Rank
	R1	R2	R3	R4	R5	R6	R7
Abrus precatorius L	2	3	3	2	3	3	3	19	5th
Aloe nobilis (L.) Burman	4	3	4	4	4	2	4	25	3rd
Chamaecrista nigricans (Vahl.)	2	5	5	3	5	2	5	27	2nd
Kedrostis foetidissima Cogn	4	2	2	3	2	3	2	17	6th
Vernonia amygdalina Delile	5	3	4	5	5	4	5	31	1st
Warburgia ugandensis Sprague	3	2	3	4	3	4	3	22	4th

Table 4.

Paired comparison on five commonly used medicinal plants used for treating malaria in Tororo District, Eastern Uganda

Name of species	Respondents										Score	Rank
	R1	R2	R3	R4	R5	R6	R7	R8	R9	R10
Abrus precatorius L	2	2	3	3	2	2	2	2	3	2	23	5th
Aloe nobilis (L.) Burman	4	3	2	2	3	3	3	3	3	3	29	3rd
Chamaecrista nigricans (Vahl.)	2	3	3	3	3	3	4	3	4	4	32	2nd
Vernonia amygdalina Delile	4	4	3	4	4	4	4	4	4	3	38	1st
Warburgia ugandensis Sprague	3	3	4	3	3	2	3	2	3	3	29	3rd

Preparation and administration of herbal medicine for management of malaria

Leaves (67.3%) were the most commonly used plant part, followed by roots (13.5%), root bark (5.8%) and fruits (5.8%) (Fig. 5). The herbal remedies are prepared through maceration (56%) and as decoctions (34%). However, they can also be powdered (6%) or prepared as infusions (4%).

Fig. 5.

Plant parts used in the treatment of malaria in Tororo district, Uganda

The herbal medicines were majorly administered orally (86.7%). Other routes of administration were topical baths (11.1%) and steam baths (2.2%). The medicaments were mostly processed and used when needed, and were rarely preserved. The most used packaging materials for liquid forms were plastic bottles (0.5–1L) and small jerricans (1–3L), whereas solids and powders were packed in polyethene bags. The plant materials were collected from the wild (46%), gardens (30%), compounds (14%) and other places (11%) such as roadsides and swamps. Most respondents (78.8%) reported that they grow the plants while others (10%) said that they purchase the herbs.

Discussion

Malaria is still a disease of public health importance in Tororo district. Our results indicate that people are familiar with malaria, and can correctly recognize it basing on the signs and symptoms. Majority of the people used TM (as opposed to MM) to treat malaria. A study on treatment-seeking behaviour and practices among caregivers of children aged 5 years with presumed malaria in rural Namutumba district (a nearby district in Eastern Uganda) showed that only 36.1% of the patients took herbal medicines. Most of them sought MM with nearly all the patients who used TM also taking modern antimalarials [30]. Further, 79.2% of the patients who used herbal medicines to treat malaria also received artemether–lumefantrine in in the same study area [30]. Hasabo et al. [31] in their study in South Sudan reported that when people fell sick from malaria, 78% of the patients sought treatment from the nearby primary health centre (MM). Although we could not ascertain the real drivers of the high use of TM in this study area, we think that apart from poverty that makes the conventional drugs unaffordable [32], the high travel restrictions instituted during the COVID-19 pandemic especially on border districts like Tororo could have forced patients to find alternative therapies of which herbal medicines are the most readily available and affordable. Additionally, they were also perceived to be efficacious and safe. The form of treatment chosen for malaria depended on its perceived severity. For the most part, uncomplicated malaria is often treated using a mixture of traditional and modern methods, and this is a common practice throughout Africa [33, 34].

This study identified 45 plant species used in Tororo district, Eastern Uganda for managing malaria. Most of the species identified has been cited for treatment of malaria in other parts of Uganda as well as other countries. For example, Albizia coriaria, Momordica foetida and Carica papaya are used elsewhere in Uganda [18, 30, 35, 36], Cameroon [37] and Zimbabwe [38]. Harrisonia abyssinica is used in Tanzania [39] and South Africa [40], while Tamarindus indica, Carica papaya and Ocimum basilicum are used in Indonesia [41]. With the exception of a few species such as Kedrostis foetidissima, Mangifera indica and Carissa spinarum, most of the plants indicated by the respondents in Tororo are used in the management of malaria and its symptoms in the neighbouring Kenya [5]. The high ICF (0.76) implies that there is sharing of indigenous knowledge related to medicinal plants use in malaria management among the community members. Hence, it is likely that the same plant species are used in the preparation of herbal medicines for malaria by majority of the people in Tororo. The dominant source of collection of medicinal plants from the wild highlights the dependence of the traditional healers on wild crafted materials. However, they are also interested in conserving the species as some collect them from gardens and the compound. The species mentioned by most people could be considered to be efficacious for the treatment of malaria and were prioritized on this basis for further analysis. A review of the available literature revealed that of the 45 plant species used in the traditional treatment of malaria in Tororo, 17 species have been evaluated for the antimalarial/antiplasmodial activity using different assays. These species possess acceptable preclinical safety and efficacy (Table 5). This confirms that indeed the reported medicinal plants possess antimalarial properties which can be further investigated for development of new antimalarial drugs.

Table 5.

Literature on antiplasmodial/antimalarial activities and toxicity of extracts and isolated compounds of the plants identified in Tororo District, Eastern Uganda

Plant name	Part used	Solvent used	Antiplasmodial (IC50 μg/ml)/antimalarial (Plasmodium strain) activities	Active phytochemicals	Toxicity	References
Abrus precatorius L	Leaves	Methanol	85.59 (D6), > 100 (W2)	Abruquinone B isolated from the aerial parts; showed antiplasmodial activity (IC50 = 1.5 μg/ml)	Two main cytotoxic constituents of leaf extract were Stigmasterol hemihydrate and β-monolinolein (IC50 = 74.2 and 13.2 µg/ml), respectively, in MDA-MB-231 breast cancer cells and cytotoxic activities. Abruquinone B was cytotoxic towards KB & BC cell lines (IC50:13.0 ± 19.8 μg/ml)	[42–44]
Albizia coriaria Welw. ex Oliver	Stem bark	Methanol	15.2 (D6); 16.8 (W2)	Triterpenoids, lupeol, lupenone	Cytotoxic to the human glioblastoma cell line U87 CD4 CXCR4 (CC50 = 6.4 and 14.9 μg/ml for ethanol and DMSO extracts	[45, 46]
Azadirachta indica A. Juss	Leaves	Water, methanol	17.9 (D6); 43.7 (W2)	Terpenoids, isoprenoids, gedunin, limonoids: khayanthone, meldenin, nimbinin	Cytotoxicity LD50 of 101.26 and 61.43 µg/ml for water and methanol extracts	[47–51]
Bidens pilosa L	Leaves	Dichloromethane, water, methanol	8.5, 5, 11, 70 (D10)	No reports	Hydro and ethanol extracts are not toxic in mice (LD50 = 12.3 and 6.2 g/kg bw), respectively. Safe in humans	[52–54]
Carica papaya L	Leaves	Ethyl acetate	2.96 (D10), 3.98 (DD2), 0.2 uM (carpaine)	Carpaine	Carpaine has high selectivity (106) and is nontoxic to normal red blood cells and rat skeletal myoblast (L6) cells	[55–57]
Cissampelos mucronata A. Rich	Root bark, root	Methanol, ethyl acetate	8.8 (D6); 9.2 (W2). Root extract- < 3.91 (D6), 0.24 (W2) for curine	Benzylisoquinoline alkaloids, curine	Slightly to moderately toxic LD50 = 288.53 mg/kg for the ethanol root extract and 8500 mg/kg for the methanol leaf extract	[45, 58–62]
Clerodendrum myricoides	Root bark	Ethanol chloroform	4.7 (D6); 8.3 (W2) > 10 (D6)	No reports	Cytotoxicity = IC50 > 20.0 μg/ml	[63, 64]
Harrisonia abyssinica Olive	Roots	Water, methanol	4.4 (D6), 10.25 (W2); 89.74, 79.50 (ENT 30); 86.56	Limonoids, steroids	Slightly to moderately toxic with LD50 of 234.71and 217.34 µg/ml for water and methanol extracts in mice	[50, 51, 60, 62]
Melia azedarach L	Leaves	Methanol, DCM	55.1 (3D7), 19.1 (W2); 28	No reports	No reports of leaf toxicity	[65, 66]
Momordica foetida Schumach	Shoot	Water	6.16 (NF54); 0.35 (FCR3)	Saponins, alkaloids, cardiac glycosides	No pronounced toxicity against human hepatocellular (HepG2) and human urinary bladder carcinoma (ECV-304, derivative of T-24) cells	[67–69]
Ocimum basilicum L	Leaves, whole plant	Ethanol	68.14 (3D7); 67.27 (INDO)	No reports	LD50 in rats was greater than 5000 mg/kg body weight. Not toxic, generally safe, LD50 = 100–5000 mg/kg body weight	[60, 62, 64, 70, 71]
Senna occidentalis L	Leaves	Dimethyl sulfoxide, ethanol	48.80 (3D7), 54.28 (NIDO); < 3	Quinones	Slightly to moderately toxic LD50 of leaf and stem extracts = 5 g/kg in mice	[60, 62, 64, 72–74]
Solanum incanum L	Leaves	Chloroform/methanol	31% parasite suppression	No report	No mortality and overt toxicity in mice at the limit dose of 2 g/kg: LD50 of both leaf and root hydromethanol extracts > 2 g/kg in mice	[75]
Tamarindus indica L	Stem bark	Water	25.1% parasite suppression at 10 mg/kg (P. berghei)	Saponins (leaves), tannins (fruits)	Not toxic	[76, 77]
Toddalia asiatica (L.) Lam	Root bark, fruits and leaves	Methanol, water, ethyl acetate, hexane	6.8 (D6); 13.9 (W2). Ethyl acetate fruit extract (1.80 mg/ml), root bark aqueous (2.43) (W2)	Furoquinolones (nitidine, 5,6-dihydronitidine), coumarins	Slightly to moderately toxic Acute and cytotoxicity of the extracts, with the exception of hexane extract from the roots showed LD50 > 1000 mg/kg and CC50 > 100 mg/ml, respectively	[45, 60, 62, 78]
Vernonia amygdalina Del	Leaves	Methanol/dichloromethane, ethanol	2.7 (K1), 9.83. In vivo parasite suppression of between 57.2–72.7% in combination with chloroquine	Vernolepin, vernolin, vernolide, vernodalin and hydroxy vernodalin, steroid glucosides	Petroleum ether extract shows strong cytotoxicity	[69, 79–83]
Warburgia ugandensis Sprague	Stem bark	Methanol, water, dichloromethane	6.4 (D6); 6.9 (W2), 12.9 (D6); 15.6 (W2) 69% parasite suppression	Coloratane sesquiterpenes, e.g., muzigadiolide	Cytotoxic to the human glioblastoma cell line U87 CD4 CXCR4 (CC50 = 7.2 and 2.0 μg/ml for ethanol and DMSO extracts	[45, 46, 79, 84–86]

Plasmodium falciparum isolates: Chloroquine sensitive strains are D6, 3D7, D10, FCR3, and NF54; Chloroquine resistant are Dd2, ENT30, FCR3, K1, NIDO, V1/S and W2

The oral route was the most used mode of drug administration. This could partly be attributed to the fact that oral dosage forms are easy to prepare and administer [5]. Like in other communities, appropriate dose determination was a challenge as many herbalists just gave estimates using cups and spoons. The preparation and packaging procedures were also prone to contamination and there was no evidence of consistency in the preparation procedures used. Hence, there is a need to sensitize the respondents about standardization procedures and good manufacturing practices so as to enhance the quality of their traditional medicine.

Conclusion

This study identified 45 medicinal plants majorly from family Fabaceae and Asteraceae used in preparation of traditional medicines for management of symptoms of malaria in Tororo district. The phytochemical constituents, antiplasmodial and antimalarial activity as well as toxicity profiles of the unstudied species with high percentage use values should be investigated to validate their uses in the management of malaria in an effort to discover novel antimalarial drugs.

Abbreviations

ICF

Informant consensus factor

MM

Modern medicine

TM

Traditional medicine

Author contributions

JRST designed the study. JRST collected and analysed the data. JRST, SBO, TO, GA wrote the initial draft of the manuscript. AN, CN, MRM and PW reviewed the manuscript. All the authors read and approved the final manuscript.

Funding

This study was funded by the Government of Uganda through the Makerere University Research and Innovations Fund (RIF 1/CAES/025).

Availability of data and materials

The raw data supporting the conclusions of this study are available upon request from the corresponding author.

Declarations

Ethics approval and consent to participate

Before commencement of the study, the study protocol was reviewed and approved by the Institutional Review Board of the College of Health Science, Makerere University (REC REF No: 2019-100). All respondents were asked for their consent and had to sign a prior informed-consent form after the objectives and possible consequences of the study had been explained to them. The prior informed consent (PIC) was written in the Japadhola language. Permission to access Tororo District for this study was given by the local area administration. Research approval was granted by the Uganda National Council for science and technology (HS 685 ES).

Consent for publication

Not applicable.

Competing interests

The authors declare that there is no conflict of interest regarding the publication of this paper.