Ethnobotanical Study of Medicinal Plants Used by Traditional Healers to Treat Cancer-Like Symptoms in Eleven Districts, Ethiopia.

There is no ethnobotanical study conducted specifically on medicinal plants traditionally used to treat cancer in Ethiopia. Yet, traditional herbalists in different parts of the country claim that they have been treating cancer-like symptoms using herbal remedies. The objective of this study was to document medicinal plants traditionally used to treat cancer-like symptoms in eleven districts, Ethiopia. Traditional herbalists were interviewed using semistructured questionnaires, and field visits were also carried out to collect claimed plants for identification purpose. Seventy-four traditional herbalists, who claimed that they knew about and/or had used medicinal plants to treat cancer-like symptoms, were selected using the snowball method and interviewed. Herbalists used their intuition and relied on the chronicity, growth of external mass, and spreading of the disease to other parts of the body, as a means to characterize cancer symptoms. Furthermore, in some of the study districts, herbalists reported that they treat patients who had already been diagnosed in modern healthcare institutions prior to seeking help from them. The inventory of medicinal plants is summarized in a synoptic table, which contains the scientific and vernacular names of the plants, their geographical location, the parts of the plants, and the methods used to prepare the remedies. A total of 53 traditionally used anticancer plants, belonging to 30 families, were identified during the survey. The most frequently reported anticancer plants were Acmella caulirhiza Del (Asteraceae), Clematis simensis Fresen. (Ranunculaceae), Croton macrostachyus Del. (Euphorbiaceae), and Dorstenia barnimiana Schweinf. (Moraceae). Organizing traditional healers, documenting their indigenous knowledge, and scientifically validating it for the development of better cancer therapeutic agents constitute an urgent and important task for policymakers and scientists.

1. Introduction

Cancer is a complex disease that is very heterogenic and variable at cellular level and also differs from one patient to the other in its behaviour, development, and outcome [1]. Physical, metabolic, and behavioural variations of cancer cells from normal ones arise through the accumulation of genetic modifications and help them to proliferate rapidly, escape from host immune surveillance, and ultimately invade distant tissues [2]. Histopathological, genetic, and epigenetic and clinical outcome variations between and within different types of cancers have been the greatest challenge to understand the disease and develop novel therapies [3].

Surgery and radiation therapy were the most preferred means of treatment to control cancer before 1950 and after 1960, respectively [4]. Chemotherapy can be done before surgery to shrink the tumor or after surgery to kill the remaining cancer cells [5]. However, most of the chemotherapeutic drugs lack specificity and tend to rapidly damage normal dividing tissues, causing side effects such as immunosuppression, neurotoxicity, and hair loss [6]. Moreover, resistance has also reduced therapeutic efficacy of some anticancer chemotherapeutic drugs [7].

In order to address these limitations, tapping nature as a major source of chemically diverse novel anticancer compounds is a consistently proven track [8]. Screening natural products yield more hit with more “drug-like” characteristics (absorption and metabolism) as compared to screening of rationally designed compounds [9]. Furthermore, screening medicinal plants based on traditional use provides a higher chance of finding active plants relative to the random approach [10].

Ethiopia has a rich and diverse heritage of traditional medical practices, known for using plants to prepare more than 90% of the remedies [11]. In addition, the country has more than 6,500 higher plant species of which, around 12% are endemic [12]. Reports indicate that up to 80% of the population relies on traditional remedies as a primary source of health care [13]. Only few ethnobotanical reports from different agroecological zones of Ethiopia are available in the literature regarding medicinal plants used for cancer treatment. These include Bersama abyssinica, Buddleja polystachya, Clerodendrum myricoides, Dovyalis abyssinica, Ekebergia capensis, Myrsine melanophloeos, Olea capensis, Pentas lanceolata, Sideroxylon oxyacanthum, and Zingiber officinale [14]; Bidens macroptera, Clematis simensis, Ferula communis, and Punica granatum [15]; Rumex abyssinicus [16]; Zanthoxylum chalybeum [17]; Phytolacca dodecandra and Vinca rosea [18]; Kalanchoe lanceolata, Stephania abyssinica, and Vernonia hymenolepis [19]; Plumbago zeylanica [20-22]; Acalypha acrogyna, Carissa spinarum, Maytenus ovatus, and Salvia nilotica [23]; Croton macrostachyus [24]; and Dorstenia barnimiana [25, 26].

In view of this fact and considering the weak traditional recording and knowledge transfer system and an alarming rate of environmental degradation, finding anticancer plants and documenting their ethnobotanical information constitute an urgent and indispensable task. Therefore, the main aim of this study was to establish an inventory of medicinal plants traditionally used to treat cancer in eleven districts of Ethiopia.

2. Materials and Methods

2.1. Description of the Study Areas

This ethnobotanical study was conducted in four national regional states of Ethiopia: Oromia, Amhara, Afar, and Southern Nations, Nationalities, and People. The survey included different districts from each region, namely, Bale Robe and Goba from Oromia, Bahir Dar Zuria and Filiklik from Amhara, Gewane from Afar, and Wondo Genet, Sodo Zuria, Doyo Gena, North Bench, Mizan Aman, and Shako from Southern Nations, Nationalities, and People Regional State (Figure 1). These geographically, culturally, and agroecologically different study areas (Table 1) were selected mainly based on the availability of traditional healers and recommendations from health workers.

Figure 1

Map of Ethiopia showing the location of study districts.

Table 1

Vegetation type, climatic condition, and demographic data of the study areas [27, 28] (source: National Meteorological Service Agency of Ethiopia).

District	Distance from capital city (km)	Approximate population (2015)	Number of interviewed healers	Area size (km2)	Geographical location	Average elevation above sea level (m.a.s.l)	Vegetation type	Climatic condition (2014)
								Annual average rainfall (mm)	Annual average temperature range (°C)
Bale Robe	432	65,284	2	8.87	7°07′11.65″ N 40°00′24.82″ E	2480	DAF	745.6	9.2–23.2
Goba	444	47,135	7	20.15	7°00′41.66″ N 39°58′33.96″ E	2614	DAF	736.3	9.5–23.8
Bahir Dar Zuria	578	206,708	16	1443.37	11°34′27.15″ N 37°21′40.87″ E	1800	CTW, DAF, and FLV/MFS	1547.1	12.7–27.6
Filiklik	188	142,722	7	806.98	10°02′12.74″ N 38°14′27.65″ E	1853	CTW and DAF	880.2	12.9–22.0
Gewane	344	39,186	6	967.85	10°29′59.99″ N 40°44′59.99″ E	568	ACB	586.7	19.5–36.7
Wondo Genet	270	196,277	12	226.45	7°05′3.01″ N 38°37′8.02″ E	1742	DAF	928.7	15–29.6
Sodo Zuria	383	145,092	2	25.62	6°51′10.11″ N 37°45′39.49″ E	1854	CTW and DAF	1569.2	14.8–25.2
Doyo Gena	258	95,393	14	130.57	7°21′20.22″ N 37°47′07.15″ E	2300	DAF	1334.5	11–22.8
North Bench	587	126,308	4	392.65	6°37′53.43″ N 35°33′56.83″ E	2367	CTW	1671.8	16–33.3
Mizan Aman	565	64,996	3	24.45	6°59′37.13″ N 35°34′55.92″ E	1441	CTW and MAF	1963.7	14.8–28.8
Shako	617	51,195	1	48,089.63 ha	7°33′42.37″ N 35°39′11.83″ E	1800	CTW and MAF	1906.9	11.4–22.4

Note. Vegetation type: DAF: dry evergreen Afromontane forest and grassland complex; CTW: Combretum-Terminalia woodland and wooded grassland; FLV/MFS: freshwater marshes and swamps, floodplains, and lake shore vegetation; ACB: Acacia-Commiphora woodland and bushland proper; MAF: moist evergreen Afromontane forest. m.a.s.l: meter above sea level; mm: millimeter; °C: degree Celsius; km2: kilometer square.

2.2. Data Collection

A team comprising a botanist and researchers from Addis Ababa University was set up, and health authorities were contacted for permission and identification of traditional herbalists living in each study area. Altogether, 117 traditional healers were approached using the snowball technique and 74 traditional healers who used herbs to manage cancer-like symptoms were selected. Ethnobotanical data were collected between January and August 2016, mainly through individual interviews with the selected traditional herbalists using a semistructured interview questionnaire. The questionnaire was prepared in Amharic language and translated to different local languages for traditional healers who do not speak Amharic. This questionnaire was designed to obtain information in the following areas: (i) general data on the informant, (ii) school attendance, (iii) use of plants for cancer treatment, (iv) source of the plant material, (v) part of the plant used, (vi) method of medicinal preparation, (vii) route of administration, and (viii) side effects.

A traditional healer for the purpose of this study is “a person who is recognized by the community in which s/he lives as competent to provide healthcare by using plants and plant products.” Each traditional healer was approached, briefed about the purpose of the research, and asked for his/her verbal consent in talking about cancer and its treatment. They were assured of the confidentiality of the information they provided. If plants were mentioned for their anticancer purposes, a botanical sample was collected. These specimens were pressed and preserved for later identification at the National Herbarium, Addis Ababa University, Addis Ababa, and a voucher specimen of each plant was deposited in the institute. All botanical names have been transcribed according to the nomenclature system used by the Plant List (http://www.theplantlist.org).

2.3. Data Analysis

The relative importance of medicinal plants used in the management of cancer-like symptoms in study areas was assessed using the relative frequency of citation (RFC), use value (UV), informants consensus factor (ICF), and cultural importance index (CI).

2.3.1. Relative Frequency of Citation (RFC)

The RFC was calculated by dividing the number of informants that cite a particular plant species (FC) by the total number of informants in the survey (N) [29]:

2.3.2. Use Value (UV)

The use value demonstrates the relative importance of plant species to treat particular ailment, and it is determined by the following formula [30]:where “UV” stands for the use value of a species, “U” stands for the number of use reports cited by informants for that plant species, and “N” is the total number of informers who reported the particular plant species i.

2.3.3. Informant Consensus Factor (ICF)

Informant consensus factor (ICF) was calculated to determine the homogeneity of the information collected about particular plant species to treat specific ailment. It was estimated using the following formula [31]:where Nur is the number of use reports of informants for particular ailment category and Nt refers to the number of species used for the ailment category by all informants.

2.3.4. Cultural Importance Index (CI)

Cultural importance index (CI) is calculated by the sum of the use reports (UR) of informants mentioning each species use (from i1 to i) in each use category and adding all the UR of each category (from u1 to uNC) divided by the total number of informants N. This index is determined by the following formula [29]:where CI is an ethnobotanical index that indicates the spread of the use along with the diversity of uses of each species.

3. Results

The informants consisted of 66 male and 8 female traditional healers and they were divided into three age groups: 20–40, 41–60, and ≥ 61 years. Out of 74 interviewed traditional healers, most of them (N%) were adults aged between 41 and 60 years. Majority of the respondents (70.2%) gained their knowledge from family members and 82% of all interviewed respondents practiced ethnomedicine for more than 25 years. More than 70% of the respondents were either only at their primary level of education or did not have a formal education at all (Figure 2). Traditional healers usually used their intuition and relied on the chronicity and growth of external mass, as a means to diagnose cancer. Lumpy growth was the most commonly cited criteria used to diagnose cancer, followed by ulcerative wounds and bleeding (Table 2). However, there were instances where some of the healers claimed to have treated patients already diagnosed with cancer at modern health institutions. Traditional healers identified cancer as “Nekersa” in Bahir Dar Zuria and Filiklik, “Naqarsa” in Bale Robe and Goba, “Sissac” in Gewane, “Xoka or Toka” in Doyo Gena, “Balamo” in Wondo Genet, “Kums or niamt” in North Bench, and “Kanser” in Sheko and Sodo Zuria district. Out of the 6 specific cancer types (skin, breast, lung, cervical, throat, and intestinal) claimed to be treated by the respondents, skin cancer was a dominant one followed by breast cancer.

Figure 2

Demographic details of the interviewed informants.

Table 2

Symptoms that are used by traditional healers to diagnose cancer.

Cancer types	Reported symptoms	Number of traditional healers
Skin	Lumpy growth	32
	Spreading pea-sized growth	1
	Ulcerative growth and oozing blood	1
Breast	Lumpy growth	17
	Lumpy growth on one breast and progressive weight loss	1
	Ulcerative wounds on breast	5
	Ulcerative wounds on breast and swelling on armpit and neck	1
	The patient was receiving anticancer treatment for breast cancer in hospital	12
Cervical	Foul-smelling bloody vaginal discharge, pain during sexual intercourse, and weight loss	1
Colon	Chronic rectal bleeding and weight loss	1
Lung	Coughing up blood	1
Throat	Coughing and swelling on the neck	1

A total of 53 plant species belonging to 30 families were reported for their anticancer use (Table 3). The result of this study showed that shrubs (49.1%), herbs (33.9%), trees (13.2%), and climbers (3.8%) were the main sources of potential anticancer medicinal plants. This study also indicated that leaves (56.7%) were the most commonly used plant parts followed by roots (21.7%), bark (6.7%), stem (1.7%), seeds (1.7%), whole plant (1.7%), leaves and roots (5%), leaves or stem (1.7%), and leaves or seeds (1.7%) (Figure 3). Most of the reported plants occurred naturally in wild (96.2%); however, cultivation was also a source (3.8%). Reported medicinal plants have been traditionally claimed to be used to treat different types of ailments including cancer. However, only few have been scientifically investigated for their antiproliferative or cytotoxic activity (Table 4). While comparing the amount and distribution of anticancer plants in the past ten years, regardless of the study areas, all respondents believed that the amount and distribution of these plants are reduced.

Table 3

List of candidate medicinal plants traditionally used for cancer treatment in the study areas.

Voucher number	Botanical name (family)	Vernacular name	Districts	Growth form	Habitat	Parts used	Preparation	Type of cancer treated	Application	UV	RFC	CI
	Acanthaceae
Bele-047	Justicia schimperiana (Hochst. ex Nees) T. Anderson	Kitkit	North Bench	Shrub	Wild	Roots	Fresh roots are crashed and boiled, and the cool decoction is drunk before meal	Lung	Oral	1	0.027	0.067
Bele-057	Justicia schimperiana (Hochst. ex Nees) T. Anderson	Gulbana	Doyo Gena	Shrub	Wild	Leaves	Fresh leaves are pounded, and the juice is applied on the affected area	Skin	Topical
	Aloaceae
Bele-060	Aloe sp.	Gurta waqota	Doyo Gena	Shrub	Wild	Leaves	Fresh roots are crashed, and the sap is applied on the affected area	Skin	Topical	6	0.014	0.081
	Amaranthaceae
Bele-044	Achyranthes aspera L.	Koch ashite	Mizan Aman	Herb	Wild	Leaves	Leaves are roasted on metal plate, pounded into powder, mixed with animal butter, and smeared on the affected part	Skin	Topical	4	0.014	0.054
	Apiaceae
Bel-046	Centella asiatica (L.) Urb.	Gorongoch	Sheko	Herb	Wild	Leaves	Young leaves are crashed, and the sap sniffed	Throat	Intranasal	2	0.014	0.027
Bel-002	Hydrocotyle mannii Hook.f	Ye'ti medhanit	North Bench	Herb	Wild	Leaves	Young leaves are crashed and applied on the affected area	Skin	Topical	1	0.014	0.014
	Apocynaceae
Bel-003	Acokanthera schimperi (A.DC.) Schweinf.	Merenz	Bahir Dar Zuria	Shrub	Wild	Leaves	Young leaves are crashed and applied	Skin	Topical	0.5	0.027	0.027
Bel-009	Carissa spinarum L.	Agam	Bahir Dar Zuria	Shrub	Wild	Leaves	Leaves are crashed and infused in cold water overnight and drunk before meal and applied on the affected area	Skin	Oral	1	0.027	0.027
	Asclepiadaceae
Bel-040	Calotropis procera (Aiton) Dryand.	Qumbo	Gewane	Shrub	Wild	Roots	Fresh roots are crashed, and the sap is applied on the affected area	Breast	Topical	3	0.014	0.027
Bel-036	Pentarrhinum insipidum E. Mey.	Barohula	Gewane	Shrub	Wild	Roots	Fresh roots are crashed, and the sap is applied on the affected area	Breast and skin	Topical	1	0.014	0.014
Bel-037	Echidnopsis dammanniana Sprenger	Mureli	Gewane	Herb	Wild	Stem	Stems are cut, and the sap is applied	Skin	Topical	2	0.014	0.027
	Asphodelaceae
Bel-020	Kniphofia foliosa Hochst.	Shushube	Bale Goba	Shrub	Wild	Roots	Dry roots are pounded, and the powder is mixed with honey	Cervical and breast	Oral	1	0.027	0.027
	Asteraceae
Bel-045	Acmella caulirhiza Delile	Kust asht	Mizan Aman	Shrub	Wild	Leaves	Young leaves are chewed by the healer and spit on	Breast	Topical	0.67	0.04	0.054
Bel-049	Acmella caulirhiza Delile	Bitisa	Wondo Genet	Shrub	Wild	Leaves	Fresh leaves are crashed and infused in cold water	Breast	Oral
Bel-030	Artemisia absinthium L.	Natrara	Sodo Zuria	Herb	Wild	Leaves	Dried leaves are ground and macerated in coffee or tea	Breast	Oral	2	0.014	0.027
Bel-029	Artemisia afra Jacq. ex Willd.	Agufa	Doyo Gena	Herb	Wild	Leaves	Dried leaves are ground and macerated in coffee or tea	Breast	Oral	1	0.014	0.014
Bel-031	Artemisia annua L.	Artemisia	Sodo Zuria	Tree	Cultivated	Leaves	Dried leaves will be ground and decocted in hot water	Breast	Oral	1	0.014	0.014
Bel-021	Cineraria abyssinica Sch.Bip. ex A.Rich.	Unknown	Bale Robe	Herb	Wild	Leaves	Fresh leaves are pounded, and the sap is applied on the affected area	Skin	Topical	1.5	0.027	0.054
Bel-058	Guizotia scabra (Vis.) Chiov.	Sheshota	Doyo Gena	Shrub	Wild	Leaves	Fresh leaves are pounded, and the sap is applied on the affected area	Skin	Topical	1	0.014	0.014
Bel-034	Solanecio gigas (Vatke) C. Jeffrey	Arbaba	Doyo Gena	Shrub	Wild	Leaves	Fresh leaves are pounded and the sap is applied on the affected area	Skin	Topical	2	0.014	0.027
Bel-025	Vernonia auriculifera Hiern	Barawa	Doyo Gena	Shrub	Wild	Leaves	Fresh leaves are pounded, and the sap is applied on the affected area	Skin	Topical	1.33	0.041	0.081
Bel-056	Vernonia auriculifera Hiern	Reji	Wondo Genet	Shrub	Wild	Leaves	Fresh leaves are chewed by the healer and spit on	Skin	Topical
	Capparidaceae
Bel-039	Cleome brachycarpa (Forssk.) Vahl ex DC.	Berbere	Gewane	Herb	Wild	Leaves	Fresh leaves are pounded, and the sap is applied on the affected area	Breast and skin	Topical	3	0.014	0.014
	Commelinaceae
Bel-026	Commelina benghalensis L.	Laluncha	Doyo Gena	Herb	Cultivated	Roots	Fresh roots are pounded, and the sap is applied on the affected area	Skin	Topical	2	0.014	0.027
	Crassulaceae
Bel-019	Kalanchoe petitiana A. Rich.	Anchura	Bale Goba	Shrub	Wild	Leaves	Fresh leaves are roasted for 2 minutes and applied on the affected area	Breast and skin	Topical	1.5	0.027	0.041
	Euphorbiaceae
Bel-012	Croton macrostachyus Hochst. ex Delile	Bisana	Filiklik	Tree	Wild	Leaves or stem	Fresh leaves or succulent stems are crashed, and the sap is applied on the affected area	Breast and skin	Topical	0.75	0.1	0.16
Bel-035	Croton macrostachyus Hochst. ex Delile	Besena	Doyo Gena	Tree	Wild	Bark	Dry bark is pounded, and the powder is applied on the affected area	Skin	Topical
Bel-048	Croton macrostachyus Hochst. ex Delile	Masichoo	Wondo Genet	Tree	Wild	Leaves	Fresh leaves are crashed, macerated in cold water, and drunk	Breast and skin	Oral
Bel-032	Euphorbia schimperiana Scheele	Gendalelata	Doyo Gena	Shrub	Wild	Roots	Fresh roots are pounded, and the sap is applied on the affected area	Skin	Topical	1	0.014	0.014
	Fabaceae
Bel-014	Albizia schimperiana Oliv.	Sessa	Filiklik	Tree	Wild	Leaves	The mixture of fresh leaves of Albizia schimperiana and Carissa spinarum is macerated in cold water for 2 days, and the macerated liquid is drunk	Breast, intestinal, and skin	Oral	4	0.014	0.014
Bel-004	Calpurnia aurea (Aiton) Benth.	Digita	Bahir Dar Zuria	Shrub	Wild	Leaves or seeds	Dry leaves or seeds are ground, macerated in cold water, and drunk	Breast	Oral	2	0.014	0.027
Bel-023	Crotalaria agatiflora Schweinf.	Unknown	Bale Goba	Shrub	Wild	Seeds	Dry seeds are ground, mixed with honey, and applied	Skin	Topical	1	0.014	0.014
Bel-028	Crotalaria incana L.	Chelke	Doyo Gena	Shrub	Wild	Leaves	Fresh leaves are crashed, and the sap is applied on the affected area	Skin	Topical	1	0.014	0.014
Bel-007	Senna singueana (Delile) Lock	Gefa	Bahir Dar Zuria	Shrub	Wild	Leaves	Fresh leaves are crashed, macerated, and drunk	Skin	Oral	2	0.014	0.027
	Lamiaceae
Bel-043	Ajuga leucantha Lukhoba	Tiks asht	North Bench	Herb	Wild	Leaves	Fresh leaves are crushed, and the sap is applied on the affected area	Breast	Topical	1	0.014	0.014
Bel-024	Leonotis ocymifolia (Burm.f.) Iwarsson	Armagusa	Bale Goba	Herb	Wild	Leaves	Fresh leaves are crashed, macerated overnight, and drunk	Breast and skin	Oral	3	0.014	0.014
Bel-054	Ocimum gratissimum L.	Mekedesisa	Wondo Genet	Herb	Wild	Roots	Fresh roots are crushed, boiled, and drunk	Skin	Oral	2	0.014	0.027
Bel-059	Pycnostachys abyssinica Fresen.	Tontona	Doyo Gena	Herb	Wild	Leaves	Fresh leaves are crushed, and the sap is applied on the affected area	Skin	Topical	2	0.014	0.027
Bel-042	Salvia nilotica Juss. ex Jacq.	Barnbanch	North Bench	Shrub	Wild	Whole plant	Dry plant parts are ground, mixed with honey, and applied	Breast	Topical	2	0.014	0.027
Bel-022	Thymus schimperi Ronniger	Tosigne	Bale Goba	Herb	Wild	Leaves	Dry leaves are decocted and drunk	Breast	Oral	2	0.014	0.027
	Malvaceae
Bel-051	Sida schimperiana Hochst. ex A. Rich.	Kotijebessa	Wondo Genet	Shrub	Wild	Roots and leaves	Fresh leaves and roots are crashed, macerated, and drunk	Breast and skin	Oral	4	0.014	0.027
	Melianthaceae
Bel-001	Bersama abyssinica Fresen.	Azamir	Bahir Dar Zuria	Shrub	Wild	Bark	Dry bark is ground, macerated, and drunk before meal	Breast	Oral	1	0.014	0.014
	Moraceae
Bel-008	Dorstenia barnimiana Schweinf.	Work Bemeda	Bahir Dar Zuria	Herb	Wild	Roots	Dry roots are ground, mixed with water and honey, and drunk, or dry roots are ground, mixed with honey, and applied on the affected area	Breast	Oral or topical	0.6	0.068	0.12
	Myrtaceae
Bel-006	Syzygium guineense (Willd.) DC.	Dokima	Bahir Dar Zuria	Tree	Wild	Leaves and roots	Dry leaves and roots of Syzygium guineense and dry leaves of Osyris quadripartita are ground, mixed, decocted, and drunk	Skin	Oral	2	0.014	0.027
	Oxalidaceae
Bel-052	Oxalis corniculata L.	Qinta	Wondo Genet	Herb	Wild	Leaves and roots	Fresh leaves and roots are crashed and applied with a bandage	Breast	Topical	2	0.014	0.027
	Polygonaceae
Bel-018	Rumex nervosus Vahl	Emboacho	Filiklik	Shrub	Wild	Roots	Dry roots are ground, macerated, and drunk	Skin	Oral	3	0.014	0.041
Bel-033	Rumex nepalensis Spreng.	Goecho	Doyo Gena	Herb	Wild	Roots	Dry roots are ground and taken with food	Colon	Oral	1.5	0.027	0.041
Bel-053	Rumex nepalensis Spreng.	Sharibicho	Wondo Genet	Herb	Wild	Bark	Fresh bark is crashed and squeezed, and the sap is applied	Skin	Topical
	Ranunculaceae
Bel-010	Clematis simensis Fresen.	Yeazo Hareg	Bahir Dar Zuria	Climber	Wild	Leaves	Fresh roots of Dorstenia barnimiana mixed with fresh leaves of Clematis simensis, pounded, and applied	Breast	Topical	0.67	0.041	0.054
	Rosaceae
Bel-011	Prunus africana (Hook.f.) Kalkman	Tikur enchet	Bahir Dar Zuria	Tree	Wild	Bark	Dry bark is ground, decocted, and drunk	Breast and skin	Oral	3	0.014	0.014
	Rutaceae
Bel-016	Clausena anisata (Willd.) Hook.f. ex Benth.	Limich	Filiklik	Shrub	Wild	Leaves	Dry leaves are ground, mixed with honey, and eaten	Breast	Oral	2	0.014	0.027
	Santalaceae
Bel-013	Osyris quadripartita Salzm. ex Decne.	Keret	Filiklik	Shrub	Wild	Leaves	Dry leaves are ground, decocted, and drunk	Breast	Oral	2	0.027	0.027
	Sapindaceae
Bel-005	Dodonaea viscosa subsp. angustifolia (L.f.) J.G.West	Kitkita	Bahir Dar Zuria	Tree	Wild	Roots	Dry roots are ground, mixed with honey, and applied or dry roots are ground, decocted, and drunk	Breast, skin and cervical	Topical or oral	1	0.014	0.041
	Simaroubaceae
Bel-017	Brucea antidysenterica J.F.Mill.	Abalo	Filiklik	Tree	Wild	Leaves	Dry leaves are ground, pasted with cold water, and applied	Skin	Topical	4	0.014	0.054
	Solanaceae
Bel-027	Discopodium penninervium Hochst.	Chechanga	Doyo Gena	Shrub	Wild	Leaves	Fresh leaves are crashed and applied	Skin	Topical	1	0.014	0.014
	Thymelaeaceae
Bel-055	Gnidia involucrata Steud. ex A.Rich.	Bito	Bahir Dar Zuria	Herb	Wild	Roots	Dry roots are ground, mixed with honey, and eaten	Breast	Oral	0.5	0.027	0.027
	Verbenaceae
Bel-050	Lantana trifolia L.	Hanshebello	Wondo Genet	Shrub	Wild	Leaves	Fresh leaves are ground, macerated in cold spring water, and drunk	Breast and skin	Oral	2	0.014	0.014
Bel-015	Lippia adoensis Hochst.	Kessie	Filiklik	Shrub	Wild	Leaves	Dry leaves are ground, macerated in cold water, and drunk	Skin	Oral	2	0.014	0.027
	Vitaceae
Bel-038	Cyphostemma serpens (Hochst. ex A.Rich.) Desc.	Eiriti	Gewane	Climber	Wild	Roots	Dry roots are ground, pasted with honey and eaten, and applied	Skin	Oral and topical	1	0.014	0.014

UV = use value; RFC = relative frequency of citation; CI = cultural importance index.

Figure 3

Frequency of plant parts used for the preparation of medicinal remedy.

Table 4

Cross-reference of cancer treatment candidate plant species collected from the study areas with the published literature.

Botanical name (family)	Biological activity/chemical constituents	Illnesses/symptoms claimed to be treated traditionally
Justicia schimperiana (Hochst. ex Nees) T. Anderson (Acanthaceae)	Saponins, alkaloids, terpenoids and flavonoids [32]In vitro cytotoxicity [33]; in vitro antioxidant activity on DPPH assay [34]; in vivo suppression of parasitaemia on Plasmodium berghei-infected mice in the 4-day suppressive test [32]; and in vivo hepatoprotective activity in mice intoxicated with CCL4 [35]	Wound [15, 21]; rabies [15, 18–20, 36–39]; jaundice [15, 16, 21, 23, 38, 40]; gonorrhea [17, 36, 39]; liver cirrhosis [18, 26]; seizure [19, 41]; stomach ache [15, 25, 38]; helminths [15, 42, 43]; skin burn/lesion [23, 44]; arthritis [21, 23]; hepatitis [45, 46]; evil eye [15, 46]; dysentery [15, 21]; malaria [36, 39]; common cold, asthma, and headache [36, 39, 47]; otitis [48]; toothache [49]; and rheumatism [50]
Aloe sp. (Aloaceae)	Anthrones and chromones [51], pyrones, coumarins, alkaloids, glycoproteins, naphthalenes, and flavonoids [52]7‐O‐methylaloeresin showed in vitro antioxidant activity in DPPH assay [51], and methanol and ethanol extract showed in vivo parasitaemia suppression on Plasmodium berghei-infected mice in the 4-day suppressive test [53, 54]	Wound [21, 55]; eye disease [21, 46, 48, 56]; snake bite [21, 48, 56]; malaria [20, 21, 44, 48, 54]; easing labour [44]; tropical ulcer, colon cleaner, and gallstone [48]; amoeba, abdominal pain, impotence, and urine retention [21]; dandruff [46, 56], hemorrhoids and hepatitis B [46]; ascariasis [21]; diabetes [54]; asthma [55]; foot strain [57, 58]; wart and anthrax [20]; external injury [59]; and liver swelling, splenomegaly, and skin inflammation [56]
Achyranthes aspera L. (Amaranthaceae)	Phytosteroids, polyphenols, and saponins [60]Methanol extracts have showed in vivo wound healing activity [61]	Bleeding [21, 24, 26, 62–64]; retained placenta [21, 62]; stomach ache and external swelling [17]; rhesus factor incompatibility in pregnancy [40, 55]; epistaxis [19]; hepatitis and evil eye [24]; tonsillitis [21, 57]; snake bite and paralysis [21]; dysentery [59]; herpes zoster [26]; anthrax [21, 49]; nasal infection and ophthalmic infection [64]; excessive menstruation and tape worm infection [15]; and gonorrhea [65]
Centella asiatica (L.) Urb. (Apiaceae)	Terpenoids (triterpenes, asiaticoside, centelloside, madecassoside, brahmoside, brahminoside (saponin glycosides), asiaticentoic acid, centellic acid, centoic acid, madecassic acid, terminolic acid, betulic acid, β-caryophyllene, trans-β-farnesene and germacrene D (sesquiterpenes), α-pinene, and β-pinene [66, 67]Methanol extract inhibited the proliferation of human gastric adenocarcinoma (MK-1), human uterine carcinoma (HeLa), and murine melanoma (B16F10) cells in vitro [68]; aqueous extracts induced apoptosis in colonic crypts and exerted chemopreventive effect on colon tumorigenesis in male F344 rats [69]	Genital infection and lymphadenitis [63]; topical swelling [26, 70]; gastritis, headache, and evil eye [70]; bleeding [40]; wound [24]; abdominal ache [71]; meningitis [72]; and tinea corporis [47]
Hydrocotyle mannii Hook.f (Apiaceae)	No previous reports	Eye infection [63] and cataract [72]
Acokanthera schimperi (A.DC.) Schweinf. (Apocynaceae)	In vitro cytotoxicity [73]; in vitro antiviral activity against coxsackie B3, influenza A, and herpes simplex type1 virus [74]; in vitro antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Trichophyton mentagrophytes [75]; and in vivo parasitaemia suppression in Plasmodium berghei-infected mice [76]	Wound [16, 44, 77, 78]; hepatitis [15, 16, 22, 44]; gonorrhea [19, 25]; evil eye [62]; bone fracture [24]; hemorrhoids [44]; scabies [21]; malaria and tonsillitis [48, 56]; psychiatric disease [55]; and skin diseases [65]
Carissa spinarum L. (Apocynaceae)	In vitro antioxidant activity on DPPH assay and in antiproliferative activity [79]	Throat cancer [23, 80]; evil eye [16, 21, 24, 49, 62, 70, 72, 81]; snake bite [23, 80]; gonorrhea [20, 65]; stomach ache [20, 70]; impotence and headache [20]; tonsillitis [17, 56, 70]; wound and febrile illness [16]; bleeding after delivery [44]; muscle cramps [49]; toothache [47]; and premature ejaculation [56]
Calotropis procera (Aiton) Dryand. (Asclepiadaceae)	Latex contains phytochemicals such as alkaloids, sterols, fatty acids, starches, sugars, oils, tannins, resins, and gums, and enzymatic proteins such as proteases, chitenases, lipases, peptidases, esterase, peroxidases, papain, hevein, and lectins [82]In vivo hepatoprotective [83]; hypoglycemic effect [84]; strong anti-implantation (antifertility) [85]; crude latex showed antioxidant and antiapoptotic activities against the toxicity of 4-nonylphenol [86]	Wound [16, 21, 81]; hemorrhoids [16, 19, 44]; wart [16, 57]; snake bite [23, 87]; kidney stone, tuberculosis, and scabies [16]; swelling [58]; skin rash [21, 49]; tinea capitis [21]
Pentarrhinum insipidum E. Mey. (Asclepiadaceae)	No previous reports
Echidnopsis dammanniana Sprenger (Asclepiadaceae)	No previous reports	Snake bite [56]
Kniphofia foliosa Hochst. (Asphodelaceae)	2-Acetyl-1-hydroxy-8-methoxy-3-methylnaphthalene, 10-(chrysophanol-7′-yl)-10-(ξ)-hydroxychrysophanol-9-anthrone, chryslandicin, knipholone, and chrysophanol [88]10-(Chrysophanol-7′-yl)-10-(ξ)- hydroxychrysophanol-9-anthrone showed in vitro antiplasmodial activity against chloroquine-sensitive 3D7 strain of Plasmodium falciparum and knipholone selectively inhibited leukotriene metabolism in in vitro a human blood assay [88]; knipholone anthrone showed in vitro cytotoxicity [89] and antioxidant activity on DPPH assay [90]	No previous reports
Acmella caulirhiza Delile (Asteraceae)	Unsaturated alkylamides like spilanthol and N-isobutylnona-2E,4E-dien-8ynamide [91]In vitro antiplasmodial activity [92]	Swelling [15]; tonsillitis [20, 63]; and toothache [40, 87]
Artemisia absinthium L. (Asteraceae)	Camphor, davanone, ethyl (E)-cinnamate, (E)-nerolidol, and chamazulene [93]Essential oils showed in vitro antiparasitic effects against promastigote and axenic amastigote forms of Leishmania donovani and Leishmania aethiopica and in vitro cytotoxicity on THP-1 (human leukaemia) cell lines [93]; and in vitro cytotoxicity on human leukaemia cell lines [94]	Hypertension, stomach ache, severe abdominal cramp [18] and sour throat [40]
Artemisia afra Jacq. ex Willd. (Asteraceae)	Epoxylinalol and dihydrocostunolide [94]; camphor, davanone, bornyl acetate, 4-terpineol, and chamazulene [95]In vitro cytotoxicity on human leukaemia cell lines [73]; and in vitro antioxidant effect on DPPH assay [95]	Stomach ache [18, 42]; evil eye [16, 17, 62]; headache [42, 77]; eye disease, tinea capitis infection, hematuria, and stabbing pain [77]; antifertility agent [33]; malaria [42, 62]; ascariasis [18]; epilepsy and febrile illness [46, 65]
Artemisia annua L. (Asteraceae)	In vitro inhibition of immune mediators of angiogenesis [96]; the sesquiterpene (Z)-7-acetoxy-methyl-11-methyl-3-methylene-dodeca-1,6,10-triene showed moderate cytotoxic activities against the human tumor cell lines of HO8910 (ovary), 95-D (lung), QGY (liver), and HeLa (cervix) by MTT assay and induced apoptosis on 95-D tumor cells [97]; artemisinin and quercetagetin 6,7,3′,4′-tetramethyl ether showed significant cytotoxicity against P-388, A-549, HT-29, MCF-7, and KB tumor cells [98]	No previous reports
Cineraria abyssinica Sch.Bip. ex A.Rich. (Asteraceae)	In vitro radical scavenging activity on DPPH assay [99]; flavonoidal glycoside (rutin) showed in vitro antibacterial activity [100]	No previous reports
Guizotia scabra (Vis.) Chiov. (Asteraceae)	In vitro cytotoxicity on human leukaemia cell lines [73], and in vitro antiviral activity [101]	Wound [20]; epilepsy [40]; and ectoparasite infestation [47]
Solanecio gigas (Vatke) C. Jeffrey (Asteraceae)	In vitro antiviral activity against human immunodeficiency virus type 1 and type 2 cytotoxicity on human T-lymphocytic MT-4 cell lines [102]	Skin diseases [62]; retained placenta [40]; hepatitis [64]; evil eye [15]
Vernonia auriculifera Hiern (Asteraceae)	Tannins, flavonoids, terpenoids, and saponins [103]	Toothache [72]; snake bite [42]; skin cut [47]
Cleome brachycarpa (Forssk.) Vahl ex DC. (Capparidaceae)	No previous reports
Commelina benghalensis L. (Commelinaceae)	Phlobatannins, carbohydrates, tannins, glycosides, volatile oils, resins, balsams, flavonoids, and saponins [104]Ethanol extract showed in vivo sedative and anxiolytic activity [105]	Helminths [65]; skin infection [72]
Kalanchoe petitiana A. Rich. (Crassulaceae)	Polyphenols, alkaloids, flavonoids, tannins, saponins, and steroids [106] In vitro antimicrobial activity against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus [75]; and in vivo wound healing activity [106]	Breast and skin cancer [107]; swelling [40, 77]; tapeworm infection, trachoma, and syphilis [77]; lymphadenopathy and evil eye [22]; sore muscles [108]; itching skin [63]; and bone fracture [23]
Croton macrostachyus Hochst. ex Delile (Euphorbiaceae)	Ethanol extract showed in vitro antioxidant activity on DPPH assay [79]	Tumor, rabies, and wart [24]; skin cancer and wound [17]; gonorrhea [20, 23, 62]; headache [18, 109]; snake bite [18, 72]; malaria [16, 18–20, 110]; helminths [18, 111]; tinea nigra [40]; ringworm [17, 62]; tinea versicolor [16, 25]; heart failure [62]; bleeding [18, 24]; hepatitis [16, 18, 24]; stomach ache [16, 18, 23]; diarrhea [16, 18]; lymph adenitis and rheumatism [18]; bloat, scabies, and urine retention [16]; retained placenta and leprosy [19]
Euphorbia schimperiana Scheele (Euphorbiaceae)	In vitro cytotoxic effect against breast cancer (MCF7), hepatocellular carcinoma (HEPG2), and cervix cancer (HELA) cells [112]	Syphilis [108]
Albizia schimperiana Oliv. (Fabaceae)	In vitro cytotoxicity on human leukaemia cells [73]	Evil eye [20]; kidney infection and liver cirrhosis [18]
Calpurnia aurea (Aiton) Benth. (Fabaceae)	3β,4α,13α-Trihydroxylupanine, calpaurine, lupinine, and epilupinine calpurmenine and calpurmenine pyrrolecarboxylic acid ester, 13-hydroxylupanine, its tiglate and pyrrolecarboxylic acid esters (calpumine), virgiline and virgiline pyrrolecarboxylic acid ester [113]; 4β-hydroxy-13α-O-(2′-pyrrolylcarbonyl)-lupanine (digittine) and 4β,13α-dihydroxylupanine [114]; alkaloids, tannins, flavonoids, and saponins [35]Methanol extract showed in vitro antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa [75] and type 1 and type 2 human immunodeficiency virus and showed cytotoxicity on human T-lymphocytic MT-4 cell lines [102]; methanol and dichloromethane crude extracts showed in vitro cytotoxicity on human leukaemia cells [73]; and ethanol extracts showed in vitro antioxidant activity on DPPH assay [79]	Tumor [22, 26, 80]; stomach ache [21, 62, 70, 81]; wound and skin infection [62]; Gonorrhoea and syphilis [16], amoebiasis [16, 80]; ascariasis and gastric ulcer [23]; diarrhea [21, 38, 70]; scabies and pubic hair louse [40]; diabetes mellitus and hypertension [19]; herpes zoster, hemorrhoids and tinea capitis [21]; and swelling and tuberculosis [58]
Crotalaria agatiflora Schweinf. (Fabaceae)	Methanol and dichloromethane crude extracts showed in vitro cytotoxicity on human leukaemia cells [73]	No previous reports
Crotalaria incana L. (Fabaceae)	Dihydrosenecionine isomer, nemorensine isomer, integerrimine and anacrotine [115]Methanol and dichloromethane crude extracts showed in vitro cytotoxicity on human leukaemia cell lines [73]
Senna singueana (Delile) Lock (Fabaceae)	Methanol extracts showed in vitro antioxidant activity on DPPH assay [116]	Stomach ache [58, 62, 70]; wound and swellings [62]; teeth infection and sprain [58]
Ajuga leucantha Lukhoba (Lamiaceae)	No previous reports	Diarrhea [70]
Leonotis ocymifolia (Burm.f.) Iwarsson (Lamiaceae)	Methanol and dichloromethane crude extracts showed in vitro cytotoxicity on human leukaemia cells [73]	Ascariasis [62], febrile illness [16, 62]; eye disease [16]; headache and neck ulcer [55]; and snake bite [15]
Ocimum gratissimum L. (Lamiaceae)	Essential oil contains constitutes γ-terpinene, β-phellandrene, limonene, and thymol and showed in vivo antiplasmodial activity against Plasmodium berghei infection [117]	Allergy reaction [18, 20]; rheumatism, headache and eye disease [18]; febrile illness and general malaise [40]; sun stroke [24]; malaria [44]
Pycnostachys abyssinica Fresen. (Lamiaceae)	No previous reports	Eye disease [18, 47]; ascariasis and wound [18]; diarrhea, stomach ache, amoebiasis, stomach bloating, and food poisoning [70]; headache [63]
Salvia nilotica Juss. ex Jacq. (Lamiaceae)	Essential oil contains germacrene D, guaiol, and trans-caryophyllene as major constituents and showed activity against both Gram-positive and Gram-negative pathogenic bacteria; the oil also showed in vitro antioxidant activity on DPPH assay [118]	Tonsillitis and constipation [62]; herpes simplex [18, 38]; wound [40]; lymphadenitis [63]; and hemorrhoids and diarrhea [65]
Thymus schimperi Ronniger (Lamiaceae)	Phenol and flavonoid compounds, and aqueous methanol extract showed in vitro radical scavenging ability, iron reducing power, and total antioxidant capacity [119]	Diabetes [62]; hypertension [18, 40]; tonsillitis [18]; toothache [18, 21]; abdominal pain [21]; and cough [38, 55]
Sida schimperiana Hochst. ex A. Rich. (Malvaceae)	No previous reports	“Shotelaye” (hydrops fetalis) [21, 22]; cough and fever [62]; diarrhea [18]; wound [25, 62]; bleeding and evil eye [24]; glandular disease and rabies [40]; amoebic dysentery, and liver disease [65]; paralysis [21]; epilepsy [43]
Bersama abyssinica Fresen. (Melianthaceae)	Flavonol glycosides isoquercetrin, hyperoside, quercetin-3-O-arabinopyranoside, kaempferol-3-O-arabinopyranoside, xanthone glycoside, mangiferin [115]Ethanol water extracts showed in vitro antioxidant activity on DPPH assay and antiproliferative activity on human liver carcinoma cell line and normal human fetal lung cells [79]; methanol extract showed in vitro antioxidant activity on DPPH assay [115], and antiviral activity against type 1 human immunodeficiency virus [102]	Tumor, dysentery and roundworms [107, 109]; ascariasis [15, 38, 81, 109]; wound [20]; stomach ache [17]; snake bite and liver diseases [70]; tonsillitis [72]; bronchitis and febrile illness [42, 43]
Dorstenia barnimiana Schweinf. (Moraceae)	Phytochemical screening showed the presence of coumarins [34]	Cancer [26]; hepatitis, syphilis and rabies [25, 26]; skin cancer, dysentery, wart and fever [25]; pulmonary tuberculosis, leprosy, and stomach illness [22]
Syzygium guineense (Willd.) DC. (Myrtaceae)	Methanol and dichloromethane crude extracts showed in vitro cytotoxicity on human leukaemia cells [73] and antimicrobial activity [120]	Stomach ache [17–19, 23]; diarrhea [15, 18, 19, 24], kidney infection, liver cirrhosis, and tonsillitis [18]; syphilis [23, 80]; malaria, hemorrhoid, internal worms, snake bite, and gonorrhea [65]
Oxalis corniculata L. (Oxalidaceae)	In vivo antitumor activity against Ehrlich ascites carcinoma on mice [121]	Wound [17]; arthritis [63]; tape worm infection [21]
Rumex nervosus Vahl (Polygonaceae)	Alkaloids, flavonoids, terpenoids, tannins, glycosides, and volatile oils [122]	Breast cancer, gastritis, and snake bite [16]; wart [15, 22]; hepatitis [49, 55]; skin rash [16, 21]; bleeding [15, 40, 81, 109]; wound [40, 49, 55, 62, 109, 110]; scabies and acne vulgaris [62]; ascariasis and herpes simplex [21]; stomach ache and dysentery [22]; diarrhea [49]; eye problems and round worm [55]
Rumex nepalensis Spreng. (Polygonaceae)	Anthraquinones, naphthalenes, tannins, stilbenoids [123]Ethanol water extracts showed in vitro antiproliferative activity on human liver carcinoma cell line and on normal human fetal lung cells and antioxidant activity on DPPH assay [79], and methanol and dichloromethane crude extracts showed in vitro cytotoxicity on human leukaemia cells [73]	Wound, ascariasis, abdominal bleeding, gastric ulcer, and hemorrhage [23, 80]; gastritis [18]; stomach problems [108]; leishmaniasis [25]; abdominal cramp and ear infection [63]; tonsillitis [18, 25]
Clematis simensis Fresen. (Ranunculaceae)	Triterpenoids, saponins, alkaloids, polyphenols, and unsaturated sterols [120]In vivo anti-inflammatory and antinociceptive activities [124]	Cancer and hemorrhoid [15]; wart and evil eye [24, 40]; wound [15, 24, 40, 63, 81]; tonsillitis [62]; eye infection [63]; leg swelling, malaria, and mental illness [49]; stomach ache [47]
Prunus africana (Hook.f.) Kalkman (Rosaceae)	No previous reports	Benign prostatic hyperplasia and prostate gland hypertrophy [20]; cancer, respiratory disorders, bad breathe, diarrhea, gonorrhea, tuberculosis, and ear problems [22]; swelling [40]; wounds [19, 22]; tonsillitis [23, 80]
Clausena anisata (Willd.) Hook.f. ex Benth. (Rutaceae)	Carbazole alkaloids, peptide derivatives, sitosterol, and stigmasterol [125]Methanol and dichloromethane crude extracts showed in vitro cytotoxicity on human leukaemia cells [73]	Skin irritation [20]; toothache [40]; ascariasis [19]; evil eye [24, 25, 63]
Osyris quadripartita Salzm. ex Decne. (Santalaceae)	Alkaloids, phenols, terpenoids, tannins, saponins, and flavonoids [126]Methanol extracts showed in vitro antimicrobial activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans, and Trichophyton mentagrophytes [11]; in vitro inhibition of NO production and cytotoxicity against MCF-7 and NCI-H460 cell lines [127]	Cancer [62]; anaphylactic shock, evil eye, and epilepsy [18]; eczema [40]; toothache [46]
Dodonaea viscosa subsp. angustifolia (L.f.) J.G.West (Sapindaceae)	Alkaloids, terpenoids, saponins, tannins, sugars, phenolics, and flavonoids [128]Methanol extracts showed in vivo nonsensitizer effect in mice using the mouse ear swelling test method [129], in vitro antiviral effect against type 1 human immunodeficiency virus [102], and in vitro free radical scavenging activity on DPPH assay [128]	Malaria [57]
Brucea antidysenterica J.F.Mill. (Simaroubaceae)	Flavonoids, amino acids, and vitamin C [130]In vitro antiplasmodial activity against Plasmodium berghei infection [131]	Cancer/tumor [107]; wart [24]; rabies [18, 62]; leprosy [62]
Discopodium penninervium Hochst. (Solanaceae)	5α,17β-Dihydroxy-6α,7α-epoxy-1-oxowitha-2,24-dienolide, withanone, and withanolide A [132], 5,6-epoxy-16-oxygenated withanolides, jaborosalactone-L, and 17-epiacnistin-A [133, 134]; 6α,7α-epoxy-1-oxo-5α,12α,17α-trihydroxywitha-2,24-dienolide and a coloratane sesquiterpene, 7α,11α-dihydroxy-4(13),8-coloratadien-12,11-olide, withanone, 5α,17β-dihydroxy-6α,7α-epoxy-1-oxowitha-2,24-dienolide, 7α,11α-dihydroxy-8-drimen-12,11-olide, withasomnine, and (E,Z)-9-hydroxyoctadeca-10,12-dienoic acid [135]Jaborosalactone-L showed cytotoxicity only to the murine macrophage cell line, RAW 264.7, but the 16α-oxygenated withanolides exhibited cytotoxicity to both human (COR-L23 and ECV 304) and murine (L929 and RAW 264.7) carcinoma cell lines with IC50 values ranging from 1.2 to 150 μM [136]. 6α,7α-Epoxy-1-oxo-5α,12α,17α-trihydroxy-witha-2,24-dienolide inhibited COX-2 and LTB4 formation; 7α,11α-dihydroxy-4(13),8-coloratadien-12,11-olide and withasomnine inhibited LTB4 biosynthesis but showed minor inhibition of COX-1 and COX-2 [135]	Skin detoxification [62]; and liver disease [70]
Gnidia involucrata Steud. ex A.Rich. (Thymelaeaceae)	Flavonoids and glycosides [137]	Ascariasis, evil eye, anthrax, intestinal helminths, and gland swelling [18]
Lantana trifolia L. (Verbenaceae)	Flavone glycosides (scutellarein-7-O-β-D-apiofuranoside and apigenin-7-O-β-D-apiofuranosyl-(1⟶2)-β-D-apiofuranoside) and the flavone celtidifoline (5,6,40,50-tetrahydroxy-7,30-dimethoxyflavone) [138, 139]	Headache [70]; malaria [71]
Lippia adoensis Hochst. (Verbenaceae)	Limonene, perillaldehyde, piperitenone, and 2-methyl-6-methylene-2,7-octadien-4-one [140], sesquiterpene hydrocarbon (germacrene D) [141]Methanol extract showed in vitro cytotoxicity on human leukaemia cell lines [73], and antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa [75]; water extracts showed in vivo protection/relieve against acetic acid induced writhing in mice model [142]	Eczema, fungal infections, common cold, and cough [62]; intestine swelling [18]; gastrointestinal disorder [40]; abdominal irritation and acute stomach illness [46]
Cyphostemma serpens (Hochst. ex A.Rich.) Desc. (Vitaceae)	No previous reports

In the current study, the highest UVs were recorded for Aloe spp. (6), Albizia schimperiana (4), Sida schimperiana (4), Achyranthes aspera (4), Brucea antidysenterica (4), Cleome brachycarpa (3), Leonotis ocymifolia (3), and Prunus africana (3). The lowest UVs were obtained for Acokanthera schimperi, Acmella caulirhiza, Cineraria abyssinica, and Gnidia involucrata (Table 3). A total of 228 use reports have been documented and categorized into seven categories (Table 5). Among these, other ailments (46.3%) and skin cancer (26.5%) had the highest use reports. Furthermore, ICF values were also calculated and ranged from 0 to 0.42. The highest ICF values were recorded in other ailments (0.42) and breast cancer (0.32) followed by skin cancer (0.23) category (Table 5). The other ailments category comprises of diseases such as stomach ache, malaria, wart, swelling, wounds, evil eye, toothache, bleeding, gastrointestinal disorder, headache, bone fracture, cough, snake bite, herpes simplex, tonsillitis, hypertension, dandruff, fever, and hemorrhoid. The ICF value of the remaining four categories (lung cancer, colon cancer, cervical cancer, and throat cancer) was zero. Quantitative ethnobotanical indexes such as RFC and CI were calculated in this study to analyze the ethnobotanical information. According to RFC values, Croton macrostachyus (0.1), Vernonia auriculifera (0.04), Clematis simensis (0.04), and Acmella caulirhiza (0.04) are the most frequently cited among all reported plants. Croton macrostachyus (0.16), Dorstenia barnimiana (0.12), and Aloe spp. (0.08) rank 1st, 2nd, and 3rd in position, respectively, according to the CI reference. Our result also shows that the Pearson correlation coefficient of RFC was positively and negatively correlated to CI and UV, respectively (Table 6).

Table 5

Informants consensus factor for different ailment categories.

No.	Category	No. of species	% of all species	No. of use reports	% of all use reports	ICF
1	Skin	25	30.5	32	26.5	0.23
2	Breast	20	24.4	29	23.9	0.32
3	Cervical	1	1.22	1	0.83	0
4	Colon	1	1.22	1	0.83	0
5	Lung	1	1.22	1	0.83	0
6	Throat	1	1.22	1	0.83	0
7	Other disease	33	40.2	56	46.3	0.42
	Total	82 ∗		121

Each plant species may be listed in several categories.

Table 6

Summary of stats for relative frequency of citation (RFC) and cultural importance index (CI).

	Mean	Standard deviation	Minimum	Maximum
UV	1.8	1.1	0.5	6
RFC	0.02	0.015	0.014	0.1
CI	0.034	0.027	0.014	0.16
Association between RFC and CI by using Pearson correlation method
	UV	RFC	CI
UV	1
RFC	−0.36∗	1
CI	0.003	0.858∗∗	1

Correlation is significant at 0.05 level. Correlation is significant at 0.001 level.

Most of the reported remedies, prepared from these plants, were either applied topically (50%) or taken orally (41.7%). The remaining remedies were prepared to be administered either topically or orally (3.3%), both topically and orally (1.7%), and intranasally (1.7%). Usually, fresh plants were finely chopped, dried, and pounded to powder form. Then, the powder of either one or the combination of more than one plant was either mixed with drinking water or pasted and applied topically. In other cases, fresh plant parts were decocted and taken orally or crushed and applied topically. Water was the main medium in preparation of most remedies and additives like honey, milk, and butter were also used. To determine the amount of plant parts used to prepare remedies, traditional healers used spoon, fingertip, and number (in case of fresh leaves). Adverse effects reported by respondents include vomiting, diarrhea, and skin ulcers.

4. Discussion

Despite the rich biodiversity of the study areas, broad acceptability, and centuries-old tradition of using traditional medicines, the number of anticancer plants reported in this study is far less than expected. As it was reported by different ethnobotanical studies conducted in different parts of Ethiopia, this could be attributed to the attitude of many traditional healers to guard their indigenous medical knowledge as a family secret and hence hesitant to share with the researchers [13, 32, 73]. Justifying the lower number of female traditional healers (8, 11%) participated in this study, these studies also inferred that traditional healers usually pass their knowledge to the first son of the family.

In this study, in agreement with the studies conducted in Fiche district [35], Ghimbi district [20], and Hawassa city [17] of Ethiopia, the predominant botanical families recorded, listing over 5 plant species each, were Asteraceae, Fabaceae, and Lamiaceae. This could be due to the fact that these families are the largest in the flora of Ethiopia and Eritrea [15, 21, 143]. Moreover, cytotoxicity studies conducted on different Mexican plants reported that the highest number of plant species with both in vitro and in vivo antineoplasic activities was from these families [20].

The highest UVs recorded in this study include Aloe spp. (6), Achyranthes aspera L. (4), Albizia schimperiana (4), Sida schimperiana (4), and Brucea antidysenterica (4). The highest ICF value (0.42) recorded for “other ailments” category, in this study, suggests that informants are in agreement with the use of particular plant species to treat ailments in this category. The lowest ICF value (0) obtained was for lung, colon, cervical, and throat cancer categories. This might be due to the cultural and ecological differences of the study sites and the difficulty to pinpoint the physical symptoms of lung, colon, cervical, and throat cancer as compared to the breast and skin cancer.

The present study also revealed that RFC and CI values of some reported species are similar. However, there is a distinct difference in species ranking using each index. C. macrostachyus is placed in the first position according to both RFC and CI index. This could be due to the fact that this species is mentioned by many informants and is the most recognized plant in most study areas. Furthermore, CI value of C. macrostachyus is also high, suggesting the diversified use of the plant. V. auriculifera and C. simensis ranked next to C. macrostachyus, according to RFC index. On the other hand, D. barnimiana and Aloe spp. ranked 2nd and 3rd by CI index. It has been suggested that UV value is a good measure of use diversity, than the number of citations [144]. In agreement with this, UV value in our study is driven by species with greatest number of use rather than those cited by more informants. The Pearson correlation coefficient of −0.36, between RFC and UV, shows significant negative association between the local importance of each medicinal plant and relative importance of use of plants. This result is in contrast to previous studies that reported a significant positive correlation between RFC and UV [145, 146]. On the other hand, there is a significant positive correlation between RFC and CI (r2 = 0.74, p < 0.001) implying that their pattern matches across species. The species with larger RFC value usually have higher CI, such as Croton macrostachyus and Vernonia auriculifera.

Leaves and roots are the most commonly used plant parts in the preparation of remedies in the study districts. Similarly, other ethnobotanical studies conducted in different parts of Ethiopia also reported that leaves are the dominant plant part followed by root [16–18, 20]. The preference towards leaves may be because leaves are the main photosynthetic organs in plants and the primary reservoirs for secondary metabolites with medicinal values [36]. In contrary to other ethnobotanical studies [17, 18], where the common use of concoctions and oral route were reported, in the current study majority of the reported remedies are prepared from a single plant species and applied topically.

Comparative analysis of this study with other ethnobotanical surveys of plants used traditionally in treating and managing cancer in Ethiopia [18], Kenya [147], Cameroon [37], Nigeria [19, 38], South Africa [39], and Bangladesh [148] revealed some similarities in the plants cited in these surveys. Of the 30 plant species cited to be used in Ethiopia [18], 7 species are identified in our study: Bersama abyssinica Fresen., Brucea antidysenterica JF. Mill., Calpurnia aurea (Ait.) Benth. Dodonaea angustifolia L.f., Dorstenia barnimiana Schweinf, Kalanchoe petitiana A. Rich., and Prunus africana (Hook. f) Kalkm.

Although herbal remedies are believed by the general public to be safe [46], some research findings suggested otherwise. For instance, traditionally used Thai anticancer plants Ganoderma lucidum (Fr.) Karst., Houttuynia cordata Thunb., and Saussurea involucrata Matsum. & Koidz. were reported to cause side effects such as headache, insomnia, constipation, and diarrhea [62]. Similarly, side effects such as vomiting, diarrhea, and skin necrosis, associated with the use of traditional herbal remedies, were reported in this and other ethnobotanical studies conducted in Ethiopia [149, 150]. Few side effects reported in this study, as compared to other ethnobotanical studies conducted in Ethiopia, could be attributed to the frequent use of the topical route of administration. Nevertheless, considering the probability of underreporting adverse effects, extensive toxicological investigations should be conducted to protect the public.

In vitro cytotoxicity and antioxidant properties of some of the plants reported in our study have also been studied. Among these plants, potent cytotoxic activity was reported for knipholone anthrone isolated from Kniphofia foliosa, with IC50 value that ranges between 0.9 ± 0.1 and 3.3 ± 0.4 μg/mL [89]. Similarly, Nibret and Wink reported the cytotoxic activity of the crude extract of Acokanthera schimperi with IC50 value of 7.1 μg/mL [73]. Studies conducted on the leaves of Cineraria abyssinica [100], bark of Senna singueana [116], and bark and leaves of Rumex nepalensis [79] also revealed potent radical scavenging activity of these plants.

5. Conclusion

The present study showed that traditional healers in eleven districts of Ethiopia use different medicinal plants to manage cancer-like symptoms. Frequency of citation value ranked Croton macrostachyus Del., Clematis simensis Fresen., Dorstenia barnimiana Schweinf, Vernonia auriculifera Hiern, and Acmella caulirhiza Del. as most cited plant species in study areas. Hence, based on these findings, we are currently evaluating the in vitro antiproliferative activities of reported medicinal plant species with a higher frequency of citation against human breast adenocarcinoma (MCF-7), human uterine cervical adenocarcinoma (SiSo), human lung carcinoma (A-427), and human bladder cancer (RT-4) cell lines using crystal violate assay. However, considering the rapid disappearance of the traditional knowledge of medicinal plants and an urgent need for new anticancer agents, additional studies have to be conducted to document and scientifically validate traditionally used Ethiopian anticancer plants.