Review on Ethnomedicinal and Pharmacological Uses of Echinops kebericho Mesfin in Ethiopia

The genus Echinops is native to African countries, the Middle East, Europe, and Asia comprises 120 species. In Ethiopia, this genus is represented by well known endemic and critically endangered species Echinops kebericho Mesfin also known as “Kebercho,” in Amharic language which has a long history of ethnomedicinal uses. Due to the popularity of species as a source of ethnomedicine, this species is severely over-harvested throughout their distributional ranges. This review documents fragmented information on traditional uses and pharmacological evidence of Echinops kebericho in Ethiopia. This review article was carried out by searching studies in PubMed, Google scholar and Google search up to August 2019. The search terms were “Echinops kebericho Mesfin”, “therapeutic” & “pharmacological”. Ethnomedicinal uses of Echinops kebericho Mesfin has been recorded from different regions of Ethiopia for 32 human and 2 livestock ailments. E. kebericho is used to treat evil eye, headache, cough, stomachache, febrile illness and malaria ailments. The extracts of E. kebericho, particularly those from root, exhibited a wide range of pharmacological effects including antihelminthic, antibacterial, antifungal, antidiarrheal, anti spasmolytic and antimalarial activities. These pharmacological studies have established a scientific basis for therapeutic uses of Echinops kebericho Mesfin. Although Ethiopian Echinops kebericho is widely used by traditional practitioners but, it is threatened due to over exploitation of root part. Therefore, E. kebericho need urgent conservation attention, micro propagation, effective documentation and further research.


Introduction
The uses of medicinal plants have been widely practiced for thousands of years to treat various diseases in all over the world [1]. More than 35,000 plant species are being used as traditional medicine around the world [2]. In developing countries, about 80% of population still relies on traditional medicine for their primary health care [3]. The African countries also have a long history and up to 90% of the human population use medicinal plants as a source of drugs [4]. Likewise, traditional medicine has played a significant role in treating various ailments in Ethiopia [5][6][7]. The current reports revealed that around 80% of Ethiopian human population still depends on medicinal plants to fulfill their primary healthcare requirements [6], largely due to its cultural acceptability of healers, relatively low cost of traditional medicine [8], and lack of adequate healthcare services suffering the larger population of the country [9]. Nowadays, medicinal plants are not only used as local and traditional aliment but also registered as official remedy that is confirmed with pharmacopoeias [10]. Furthermore, a photochemical screening, often leads to the discovery of new compounds that can play a significant role in the global efforts against various ailments [11]. More than 50% of all modern drugs have natural origin; therefore, these products have a great role in the pharmaceutical sciences for drug development [12]. The current investigations have indicated that around 25% of the modern remedies have been obtained from medicinal plants [13].
Echinops kebericho Mesfin is also a plant with immense medicinal values with restricted distribution in Ethiopia. It is an erect enormous root stock-bearing perennial herb or shrub that grows up to a height of 1.2 m with leafy stems [14]. It is a well known endemic and critically endangered medicinal plant belonging to family Asteraceae. Echinops kebericho has been used for curative and therapeutic properties intreating various infectious and non infectious diseases such as fever, headache, stomachache, malaria, and cough [15]. In the pharmacological action E.keberichoroot extracts have also been reported forantihelmintic, antitumor, antimutagenic, antibacterial and fungicidal properties [16,17]. In addition, extracts and essential oils of the roots were shown to have antimicrobial, antihelminthic, molluscicidal and in vivo antiplasmodialactivities [15,18]. Current investigation has identified that E. kebericho have been reported to control veterinary and agricultural insect pests [19]. Because of their versatile biological and therapeutic activities, E. kebericho plants have been traditionally used for the treatment of various diseases in different parts of Ethiopia. However, there has not been any review conducted on therapeutic and pharmacological uses of Echinops kebericho to treat various diseases. Therefore, the present review compiles the fragmented information on the traditional and pharmacology uses of the Echinops kebericho species. This information will highlight the importance of the genus and will provide baseline information for future researchers intending to do further work on genus Echinops.

Results
The present review reported the majority of studies were in Oromia region located in the central part of Ethiopia. In most of the reported studies, the majority of informants were men (traditional healers, laypeople and experienced elders) at the ages between 35 and 85 years. In almost all studies, number of informants or interviewees was above 30. Mostly, field surveys, group discussions, and semi structured questionnaires were carried out from local inhabitants to collect the data. However, in some of the studies, direct interviews were also observed. A brief overview of the results is presented in the following sections.

Botanical Features and Distribution of Echinops Kebericho Mesfin
In Ethiopia, E. kebericho known by common name "Kebercho" in Amharic language [20,21]. Echinops kebericho Mesfin belongs to the Asteraceae family, known only in Ethiopia, is an erect massive root stock-bearing perennial herb or shrub that grows up to a height of 1.2 m with leafy stems [22]. The leaf lamina is curved and is detached into pieces that consistently end in spikes. The corolla is white or brilliant blue [23]. Flower head 3-4 in diameter, spineless peduncle up to 5.5 cm long, arachnoid, pubscent, 1-2mm wide. Echinops kebericho, is endemic and critically endangered medicinal plant in Ethiopia.
Literatures reviews revealed that, 38 studies focused on genus Echinops, were found to be therapeutically evaluated. Among the genus Echinops known for medicinal value in Ethiopia, more than half (63%) of the genusbelonging to family Asteraceae (Echinops kebericho Mesfin) was confirmed for its therapeutic potentials. Echinops kebericho Mesfin [24][25][26][27][28][29][30]. The majority of Echinops kebericho Mesfin uses reported in Oromia (52%), Amhara (30%) and SNNPR (11%) regions [31][32][33][34][35][36][37][38]. The Oromia and Amhara regions share boundaries with many other regions in Ethiopia and are likely to share common flora and cultural practices, including in ethno-medicine. This long list of species also indicates that local people in these regions have an active interest in E. kebericho species. Moreover, the geographic distribution of Echinops kebericho Mesfin is likely to be predicated on local trend with regard to cultural and floral diversity including traditional medicinal practices. [39], and [40], reported that the plant belongs to the genus Echinops that comprises 125-130 species in the family Asteraceae/Compositae distributed in semi-humid zones of tropical and North Africa, Mediterranean basin, and temperate regions up to Central Asia. The twelve species of E. kebericho belongs to the Asteraceae family occur in Ethiopia are also confined to the highlands of the country between 7 o 30' N and 38 o 45' E and at altitudes between 1700 and 2900 m.a.s.l [41]. E. kebericho grows in dry and stony lateritic soils. It is different in habit and in dissection of the leaf blade. These plant populations in deep vertisols are low shrubs whereas those growing in dry, stony lateritic soils are perennial herbs [41].

Therapeutic Uses of Echinops Kebericho Mesfin
A survey of literatures showed several medicinal properties have been attributed to Echinops kebericho Mesfin in different regions of Ethiopia. The traditional uses of Echinops is referred to many folkloric and ethnobotanical studies done in Ethiopia, where the species is still used as primary sources of traditional medicine. A total of 32 human and 2 animal ailments are treated with Echinops kebericho (Table 1). [51] and [53] also showed the majority of medicinal plants were used to treat human diseases than livestock due to high prevalence of human diseases. But, [26] observed that local communities give priority for human health care than livestock due to inadequate modern healthcare centers in the study area till traditional healers are using local plants for the welfare of human health. The most commonly treated human ailments are evil eye followed by headache, cough, stomachache, febrile illness and malaria. Other studies conducted elsewhere in Ethiopia indicated the evil eye as common mental disorders [24,54,55]. The previous study in Dega Damot, Amhara, North western Ethiopia also showed that 34% of informants reported Echinops kebericho used to treat evil eye in the district [37]. Similarly, study around Dirre Sheikh Hussein, South-eastern Ethiopia [53] found that, Echinops kebericho Mesfin was frequently mentioned medicinal plant. The comparison of earlier ethnobotanical studies conducted in Ethiopia showed that, many similarities can be recognized when the ethnomedicinal uses of Echinops kebericho is considered in all regions (Table 1). This may imply that, local people of Ethiopia over wide area have the tendency to use the similar medicinal plant as a result of the wider distribution of medicinal plants in the country [33] and due to same selection criteria. On the top of this, similar uses of Echinops kebericho in different regions of country also showed the considerable dissimilarity with respect to preparation and application techniques. According to this review, traditional medicinal practitioners in Ethiopia apply different techniques of preparations including, crushing, powdering, and chopping (Table 1). They use simple techniques and equipments during their remedy preparation. For instance, powder of Echinops root is given to patients suffering evil eye by inhaling and roots are crushed with seeds of Guizotia abyssinica, mixed with water and solution taken orally [32,34,37,42,46]. Medicinal preparations from Echinops kebericho Mesfin have been suggested to shorten the course of illness from black leg, respiratory manifestations and liver disease [38]. Moreover, the smoke from burning the plant is inhaled to relieve headache [27,31,32,34,44,50]. Echinops kebericho is traditionally used for the treatment of fibre illness, evil spirit, snake bite, tonsillitis, coughing and sudden illness [35,36,43,56].
Traditional healers prepare herbal remedies either solely or in combinations and for oral use with water or other additives such as honey, sugar and mixing with other plant. The majority of the Echinops kebericho remedies (87.3%) are used as monotherapies. The review is in agreement with the finding of [53], which stated that single plant remedy preparations were high. However, multi therapies/ a mixture of Echinops kebericho root pounded together with leaf of Vernonia amygdalina given for cattle as a remedy for parasite [27]. Pounded dry root is mixed with coffee used for headache [31]. E. kebericho roots are crushed with seeds of Guizotia abyssinica, mixed with water and solution taken orally for treatment of malaria [46]. The use of multiple therapies in traditional medicine based on combining plants has recently been shown to increase the efficacy of the herbal medicine [57]. Study by [58], showed that the use of more than one plant species to prepare a remedy for ailments is attributed to the synergistic effects that they could have during ailment treatment.
In this review, root was the most commonly used plant part in the preparation of remedies as compared to other parts. [6,48,59] also found roots take the highest proportion in remedy preparation due to the efficacy of roots in treating the ailments. Study conducted in South Omo, Southern Ethiopia [60], indicated that roots remain in the soil and is easily available, even during the long dry seasons in arid and semi-arid areas. Moreover, the use of plants root could also be associated with early African beliefs in their powerful therapeutic effect to protect malaria and venereal diseases and to induce abortions [61,62]. However, other studies conducted elsewhere in Ethiopia showed harvesting root of a plant poses more threat to survival of plant than collecting other parts such as fruits, seeds and leaves [63,64]. Similarly, [65], found that Echinops kebericho was a critically endangered medicinal plant due commercial harvesting and sale of roots. Moreover, study conducted in West Gojjam Ethiopia [33] revealed that Echinops kebericho was approaching to extinct due to overharvesting root for medicine. But a study done in Guraghe zone, SNNPR of Ethiopia [66] indicated that 66% of Echinops kebericho threatened because of agricultural expansion.

Antimicrobial Activity
The present review reported the extract of E. Kebericho root exhibited good antibacterial and antifungal activity. Report says that alcohol extracted from E. Kebericho root believed to be responsible for control against S. aureus A. flavus and C. albicans [67]. But, water based extracts showed weak antimicrobial activity. The higher polyphenols present in alcohol based extracts was found to posses stronger antimicrobial activity than water based extract.

Antimalarial Activity
Malaria is a world public health threat infecting about 300 million people each year [68]. Thus, medicinal plants are being commonly used to treat malaria due to the presence of anti plasmodial compounds [69]. Experiments by [70], demonstrated that E. Kebericho root extract in fraction of hexane and butanol have antimalaria activity with an optimal dose of 500 mg/kg body weight. Root extractof E. Kebericho in crude ethanol showed parasitemia and extending the survival time of mice [15]. The extracts of E. Kebericho showed antiplasmodial activities against Plasmodium Berghei which supports traditional uses of species [71]. E. Kebericho Mesfin is also among traditionally used medicinal plants against wide ranges of diseases including malaria in Ethiopia [18,72], showed that Sesquiterpenes compounds obtained from Echinops species exhibited antimalarial agents activities.

Antidiarrheal and Ant Spasmolytic Activities
Diarrhea is a widespread gastrointestinal disorder caused by infections. It is responsible for deaths of 5 million human populations every year [73,74]. The present review reported the root extract of Echinops kebericho is used traditionally for the treatment of diarrhea in Ethiopia. [75], conducted an experiment with aqueous extracts from E. kebericho for its protective effect against diarrhea and spasmodic. This research confirms the use of extract of Echinops kebericho possesses antidiarrheal and spasmolytic activities.
According to [76] flavonoid is collection of polyphenolic compound and has been confirmed to exhibit a different of biological activities for example antioxidant, anti-inflammatory, antispasmodic, and antidiarrheal effects. Study by [77] reported that the antidiarrheal activity of flavonoids to inhibit intestinal motility and hydro-electrolytic secretions.

Oral Acute Toxicity Activities
Many plants produce biologically active substance which can poison, kill and repel other species. [71] demonstrated that the graded doses of 70% methanol extract of E. Kebericho Mesfin did not exhibit any signs of toxicity in mice. Experiments by [15] confirmed that E. kebericho extract in hydro-alcoholic did not produce significant changes in behaviors, such as alertness, motor activity, breathing, restlessness, diarrhoea, convulsions, coma, and appearance of the animals. Research by [78] showed that the people in the central and south-western parts of Ethiopia use the smoke of E. kebericho to repel snakes from their vicinity. These results confirm that natural products from Echinops species are potential sources of new and selective agents for the treatment of important diseases.

Antileishmanial Activity
Leishmaniasis is a disease caused by obligate intracellular parasitic protozoa of the genus Leishmania [79]. According to [80], leishmaniasis is transmitted to humans and other mammals by the bite of infected females and flies vector. For the past decade, there have been a few studies conducted concerning the antileishmanial activity of phytochemicals of Echinops kebericho. In one pharmacological study, essential oils extract of Echinops kebericho was found to be highly active as antileishmanial activities [17].

Major Threats to Echinops Kebericho
Currently, many medicinal plants are being seriously depleted in Ethiopia due to anthropogenic factors [45,81], agricultural expansion, deforestation, fuel wood harvesting, overgrazing and urbanization [82,83]. Echinops kebericho has been registered under national red list as vulnerable since it is facing a high risk of extinction in the wild, mainly associated with its traditional medicinal use [84]. Study conducted in Tembaro Zone, Southern Ethiopia [85] showed that Echinops kebericho, was marketed mainly for therapeutic purpose to generate income. The first report made by [86] revealed the popularity of E. kebericho trade in all 19 markets of central parts Ethiopia. The numerous tuberous roots are sold as small pieces or in entire in many markets in Gojjam, Shewa and Wellega [29]. According to [87], the use and practices related with traditional fumigation of E.kebericho isa vital after birth in many parts of Ethiopia. For instance, a study in Borana, southern Ethiopia showed that E.kebericho has been reported to have abortifacation effect, and also used to care forepilepsy, epistaxis, atrophy, sudden, evil spirit sickness by people of Kembatta, Southern Ethiopia [85]. Thus, due to its over use in the wild the species is facing a high risk of extinction in the wild.
Echinops kebericho Mesfin is known as seriously endangered endemic shrubs of Ethiopia [88]. Study conducted in Mecha Wereda, West Gojjam Zone of Amhara region [14], indicated that E. kebericho is insufficient medicinal plant due to overexploitation. Moreover, the natural regeneration status of E. kebericho is restricted to a particular microclimate; the domestication of this species is very difficult. E. kebericho reproduce by seed which is incompetent due to inadequate and in viability of seeds. Propagation by seeds is time consuming to achieve large scale production for preservation and farming of the species. Despite these problems, the local people destruct the whole plant before seed set as they use the root part for medicinal use. Generally, a problem related with natural propagation and overexploitation for medicinal use has put E. kebericho in the list of critically endangered plant species of Ethiopia [89]. It is among few prioritized medicinal plants of Ethiopia that needs urgent conservation. The micropropagation of E. kebericho is very useful to preserve germplasm of this endangered species, to promote scientific activities, commercial cultivation and sustainable usage of the species. Study by [90], reported the in vitro and ex vitro seed based propagation of E. kebericho. Other study has also showed that micropropagation of Echinops kebericho has a considerable practical significance for large scale production of plants for their rehabilitation in natural habitat, ex vitro cultivation and sustainable utilization of this medicinal plant [65].

Conclusion and Recommendations
The extensive literatures survey revealed that Echinops kebericho Mesfin is important medicinal plant with diverse pharmacological spectrum. The plant shows the presence of many chemical constituents which are responsible for varied pharmacological and medicinal properties. The pharmacological analysis will also highlight how the limited population numbers of the plant can be utilized as source of medicine. Although Ethiopian Echinops kebericho is widely used by traditional practitioners for curing various diseases, it is threatened due to over exploitation of root part; hence urgent conservation attention is needed to conserve this species for sustainable usage in the future. Moreover, the present researchers believe that the therapeutic use of the E. kebericho will provide basic data for further researches focus on pharmacological studies and the conservation of this most endangered and endemic medicinal plant in Ethiopia.

Authors' Contributions
Gadisa Demie is a lecturer at Department of Forestry College of Agriculture and Veterinary Science, Ambo University, Ethiopia. He planned the Review, searched data, analyzed the data and wrote the manuscript.