Ethnopharmacological survey of medicinal plants used to treat cutaneous leishmaniasis in Ain Sekhouna, Saida, Algeria

Cutaneous leishmaniasis is a common anthropozoonosis and a major public health problem in Algeria. Therefore, we conducted an ethnopharmacological survey in the locality of Ain Sekhouna (located in the highlands of western Algeria), one of the foci of cutaneous leishmaniasis. We aimed to identify the medicinal plants and natural remedies used by the local population to treatment cutaneous leishmaniasis. We identified three plant species, belonging to three distinct families, used as natural remedies against the disease, namely, Haloxylon scoparium Pomel (Chenopodiaceae, 73%), Artemisia herba-alba Asso. (Asteraceae, 18%), and Camellia sinensis L. (Theaceae, 9%). Additionally, 35% of the plant-based medicines mostly comprised the powdered form of the aerial parts of the plant. According to the respondents, the powder is combined with butter, cade oil, or honey and is applied exogenously on the skin. Overall, these medicinal plants can be used as a source of natural medicines, in combination with commonly used dermatological excipients, to treat cutaneous leishmaniasis.


Introduction
Cutaneous leishmaniasis (CL), a global public health problem, is endemic to more than 70 countries, with an estimated annual incidence of 1,500,000 individuals (Bhutto, 2003;Jones, 2005). Cutaneous leishmaniasis is caused by the infection of a flagellated protozoan (Kinetoplastea of the genus Leishmania), which is transmitted by the bite of a small hematophagous midge of the subfamily Phlebotominae.
Cutaneous leishmaniasis is a serious public health concern in Algeria. The recrudescence and spread of the disease to regions close to the foci of infection necessitates an increased surveillance of the evolution of this zoonosis and the application of adequate control measures (Harrat et al., 1995).
The first-line treatment of CL involves the administration of pentavalent antimony salts, 8.5% Nmethyl-D-glucamine and 10% sodium stibogluconate, by a health provider, and they are available in the form

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Notulae Scientia Biologicae of injectable ampoules. It is recommended to evaluate the cardiac, renal, and hepatic statuses of patients before and during treatment, because high doses of pentavalent antimony salts can cause health problems such as cardiotoxicity and nephrotoxicity (McGwire and Satoskar, 2013). In addition, some strains of Leishmania responsible for CL and mucocutaneous leishmaniasis exhibit resistance to these drugs (Grogl, 1992). Phytotherapy, that is, the treatment of diseases and infections with plants, has been used for centuries, and medicinal plants have been as a source of medical care in developing countries (Tabuti et al., 2003).
According to the World Health Organization, more than 80% of the African population uses traditional medicines and pharmacopeia to address health problems (Sahli et al., 2010), because medicinal plants not only possess healing properties, but also support proper functioning of the human body (Bigo, 2011). Algeria is a Mediterranean country with an age-old medical tradition and a population with conventional knowledge of medicinal plants. There are several studies on various plants used to treat a wide range of diseases in Algeria (Benarba et al., 2015;Miara et al., 2018;Hamza et al., 2019). However, only a few studies have reported the use of medicinal plants to treat CL. Therefore, in the present study, we aimed to identify medicinal plants that are effective against CL and could be used as alternatives to the drugs used to treat CL, which have severe adverse effects.

Study area
The study was undertaken in the municipality of Ain Sekhouna (34° 30' 26'' N, 0° 50' 46'' E; altitude: 900 m) (Figure 1), which is located to the south of Saida in Algeria and is approximately 90 km long, with an important hydrographic network. It covers an area of 404.40 km 2 (15% of Sebkha). The commune of Ain Sekhouna is surrounded in the north and west by the commune of El Maamoura, on the east and north by the wilaya of Tiaret, and on the south by the wilaya of El Bayadh (Anteur, 2016).
The climate of Ain Sekhouna is semi-arid, with cold winters and hot summers. The average annual temperature is approximately 14.8 °C and the average annual rainfall is 276 mm, distributed over 47 d. The average relative humidity ranges from 74.5% in December to 37% in July, and the area is subjected to strong winds that blow from the northwest in winters and from the south in summers. Siroccos are frequent, and they last for an average of 22 d per year. Population surveyed A total of 100 people (approximately 3% of the population) out of 3,500 inhabitants, 68 women and 32 men of different ages, were interviewed. The survey parameters and the interviewees' responses were recorded in the form of a questionnaire ( Table 1) that was provided to the respondents during the interview. During the interviews, information on the medicinal plants used to treat CL, along with the profile of each respondent, including their sex, age, level of education, and the origin of their information on the plants used, was collected. Moreover, the data collected for each plant included the part used and preparation method of the remedy. Taxonomic identification of each species was carried out by the botanists of the Biology Department, University of Saida, using botanical descriptions from literature.
The information recorded on raw data sheets was transferred to a database, processed, and analyzed (Benabdesslem et al., 2017).

Results
Medicinal plant species used to treat CL All respondents of the interviews were literates, with different levels of education (22% university-, 65% secondary-, and 13% primary-levels). Each respondent claimed to have some prior knowledge of CL and conventional medicinal plants used to treat CL. Moreover, 68% of the respondents claimed that at least one member of their family was previously affected by CL.
Based on the survey, the following three plant species were identified for treating CL (Figure2): Haloxylon scoparium Pomel, reported by 73% of the respondents, followed by Artemisia herba-alba Asso.
(Asteraceae) and Camellia sinensis L. (Theaceae), reported by 18% and 9% of the respondents, respectively. Haloxylon scoparium was reported as an effective treatment for CL by the respondents of all age groups, with the maximum use by people aged 50-60 years (22% respondents). Artemisia herba-alba was mostly used by individuals in the age group of 30-40 years (7.5% respondents), whereas, Camellia sinensis was used by individuals of different age groups (not exceeding 2.5% of the respondents) ( Figure 3).

Parts of the medicinal plant species used to treat CL
The survey revealed that the aerial parts of the three plant species were predominantly used to treat CL: H. scoparium, 35% and A. herba-alba and C. sinensis, approximately 10% (Figure 4). The powdered medicinal preparations were administered alone or in the form of a poultice. The powdered plant or plant parts were mixed with butter, olive oil, honey, or cade oil to prepare a homogeneous paste, which was applied exogenously on the infected epidermis multiple times.

Discussion
The objective of the present study, conducted in the locality of Ain Sekhouna, Saida (southwest Algeria), was to identify plants used to treat zoonotic CL (also known as "Biskra nail"). Cutaneous leishmaniasisis caused by a flagellated protozoan Leishmania major and transmitted by Phlebotomus papatasi Scopoli (Diptera: Psychodidae). It was first described by Hamel in 1860; CL is endemic throughout the North Saharan fringe of the arid and semi-arid bioclimatic zone (Bachi, 2006). Although antimony salt-based treatment is used for leishmaniasis in the Algerian convergence, the Algerian population uses traditional medicines as an alternative to antimony salt-based medicines to prevent, limit, and treat super infections resulting from the disease.
This ethnopharmacological survey conducted in Ain Sekhouna is the first survey in the study area, wherein 100 interviewees identified three plant species that are used to treat skin lesions in CL. Moreover, H. scoparium was identified as the most widely used species for the treatment of CL in the study area by 73% of the respondents. These results agree with those of El Rhaffari et al. (2002), who showed that H. scoparium is the most cited plant species used to treat CL by the local population in the Oasis of Tafilelt, Morocco. This species is known for its pharmacological and biological properties and contains many bioactive compounds such as alkaloids (Li et al., 2010) and phenolic compounds (Haida et al., 2020), which are lethal to the promastigote form of Leishmania and prevent flagellum formation in macrophages (Mahmoudv et al., 2014) or inhibit the arginase activity that maintains the Leishmania population in the host (Manjolin et al., 2013). A total of 8% and 9% of the respondents identified A. herba-alba and C. sinensis for the treatment of CL, both of which are used as plants with anti-leishmanial activity in their homes. Although members of the families Asteraceae and Theaceae have been used in traditional medicines to treat dermatological diseases (Salhi et al., 2010;Zeggwagh et al., 2013;Vandi et al., 2016), to the best of our knowledge, there have been no studies on the anti-leishmanial potential of C. sinensis.
The present survey also revealed that the aerial parts of the identified plant species constituted a major portion of the treatment (10%-35%). These findings are similar to those of previous studies (Jaradat et al., 2016;Wubetu et al., 2017). The use of these species and their parts can be explained by the fact that they are easily harvested (Doukkali et al., 2015) and their leaves are rich in biologically active secondary metabolites (Benabdesslem et al., 2017).
According to all the respondents, the powdered form of the medicinal preparations, which is applied exogenously as a poultice on the infected part of the epidermis, is the recommended mode of application. Previous studies on traditional medicines revealed that the poultice method of remedy preparation and external  , 2017). This can be explained by the speed and efficacy of the poultice method, both of which depend on the type of disease and infection (Al-Qura'n, 2009;Zeouk et al., 2018). Furthermore, the remedies were prepared in butter, cade oil, olive oil, or honey to facilitate their action (Uzuna et al., 2004). These excipients are commonly used for dermatological treatment owing to their remarkable pharmacological and cosmetic properties (Koruk et al., 2005;Fontanel, 2012;Domerego et al., 2016).

Conclusions
In this study, we evaluated the use of plants to treat CL by the population of Ain Sekhouna; the study offered a practical approach to describe, valorize, and preserve local pharmacopeia, thereby preventing its uprooting.
The population of Ain Sekhouna exploits the biological properties of H. scoparium, A. herba-alba, and C. sinensis to prevent and treat CL. The preparation and administration of the remedies, that is, exogenous use of cataplasm, fit the logic of the galenic system. Overall, the findings of this study encourage further research in the field of phytochemistry, with the aim to identify novel natural active principles that can be used in pharmacology.

Authors' Contributions
Conceptualization and methodology: MMH and KH; Investigation: AA; Formal analysis: KH and MMH; Writing -original draft: AA and KH. All authors read and approved the final manuscript.