Aromatic and medicinal plants used in traditional medicine in the region of Tiaret, North West of Algeria

. Herbal medicine is gaining an increasing importance in the management of various ailments, but little is known about traditional practices in Algeria. This ethnopharmacological study aims to document medicinal and aromatic plants used in traditional medicine in the region of Tiaret (northwest of Algeria) in order to contribute to safeguard the local pharmacopoeia as cultural heritage, and to provide a scientific basis for developing novel strategies for such practices which can help for drugs discovery. Semi-structured interviews with 64 traditional healers and herbalists were realized in the region of Tiaret (Algeria) throughout field studies achieved from December 2018 to May 2020. Interviews covered sociodemographic information, popular and vernacular names of the medicinal plants, mode of use and toxicity among other data. Results reveal the use of 107 plant species belonging to 45 families and 97 genera for the treatment of various ailments. Lamiaceae, Apiaceae and Asteraceae were the most represented families. The most frequently cited species were Senna alexandrina Mill. (FC=27), Atriplex halimus L. and Bunium incrassatum Amo (FC=23 each), Foeniculum vulgare Mill. (FC=22), and Matricaria chamomilla L. (FC=21) . However, the higher use values were reported for Nigella sativa L. (UV=1.5), Trigonella foenum-graecum L. (UV=1.38), Thymus serpyllum L. (UV=1.2), Ziziphus lotus (L.) Lam. (UV=1.14), Urtica dioica L. (1.13), and Senna alexandrina Mill. (UV=0.52) respectively. Interestingly, Bunium incrassatum Amo, Echinops spinosissimus Turra, Cucurbita moschata Duchesne, Pennisetum glaucum (L.) R.Br and Malus domestica Borkh. were reported for the first time as medicinal plants in the north Africa and Algeria. Moreover, 246 new therapeutic uses were described. It should be noted that Pistacia atlantica Desf. , Tetraclinis articulata (Vahl) Mast., Oudneya africana R. Br. , Euphorbia guyoniana Boiss. & Reut , Teucrium polium L. and Marrubium deserti (Noë) Coss. are endemic to North Africa-Algeria, Northern and Central Sahara. Furthermore, Artemisia herba-alba Asso , Anacyclus pyrethrum (L.) Lag., Cuminum cyminum L., Saussurea costus (Falc.) Lipsch., Boswellia sacra Flueck. and Pistacia atlantica Desf. are considered threatened, rare or endangered species. Our findings are relevant not only for the future studies and experiments in the search for novel compounds, but also for the safeguard of traditional knowledge and biodiversity.


Introduction
The use of aromatic and medicinal plants and their derivatives for food and therapeutic purposes is very common worldwide since ancient times. Currently, almost 80% of the world's population, mainly in developing countries, depend on herbal medicines to answer their basic primary health needs for the management of numerous diseases (WHO, 2004(WHO, , 2018. The difficulties to obtain essential health services along with the failure of modern medicine in finding effective treatments for several diseases have promoted remarkably the resurgence of traditional medicine (Taïbi et al., 2020a). In addition, the indiscriminate use of chemicals and synthetic drugs led to the emergence of pathogenic multidrug resistant microbes responsible of severe health issues (Ait Abderrahim et al., 2017).
In Algeria, phytotherapy constitutes an integral part of the local culture of population which holds an important knowledge acquired empirically from a generation to another. Indeed, Algeria is characterized by a very rich and highly diversified flora due to its geographical location and the significant diversity of its climatic and topographic conditions (Azzi et al., 2012;Berrabah et al., 2019;Boussaid et al., 2018;Makhloufi et al., 2021;Makhloufi et al., 2020). The diversity of plant taxa is represented by 3183 plant species which constitutes an important opportunity for focused screening of biological compounds based on traditional usages (CBD, 2020;Taïbi et al., 2020a) Indeed, the ethnomedicinal approach resulted in the search of aromatic and medicinal plants as a promising source of various bioactive compounds which constitutes the basis of new drug discovery with less or no side effects. Therefore, ethnomedicinal and ethnopharmacological studies are very required to disclose local medicinal plant species, and to document and save local popular knowledge (Orhan, 2014). Although numerous ARTICLES ethnobotanical and ethnopharmacological studies have been undertaken in various region in Algeria (Azzi et al., 2012;Benarba, 2016;Benarba et al., 2015;Benderradji et al., 2014;Boudjelal et al., 2013;Ouelbani et al., 2016;Sarri et al., 2014Sarri et al., , 2015Taïbi et al., 2020a, b), this field of study remains insufficiently covered to document the huge diversity of taxa and ancestral knowledge. Also, there is an urgent need to develop a national pharmacopoeia besides national standards and guidelines of collect and uses. Moreover, the collected data are being used as basis in research that needs to be tested in clinical and lab trials.
In this context, the current study is an ethnopharmacological investigation aiming to document the use of traditional medicines based on aromatic and medicinal plants used by traditional healers for the management of various ailments in the region of Tiaret (North West of Algeria). To our knowledge, this is the first ethnopharmacological investigation carried out in the region on high number of herbalists and traditional healers. The obtained data are believed to enrich national and world's databases of traditional knowledge and safeguard the cultural heritage as recognized by the UNESCO in 2003.

Study area
The present study is achieved in the region of Tiaret, northwest of Algeria. Interrogated residing population is distributed mainly in nine principal towns i.e., Ain Deheb, Frenda, Ksar Chellala, Medroussa, Mehdia, Rahouia, Sougueur, Thekhmaret and Tiaret besides numerous villages nearby (Figure 1). The study area includes a part of the Tell Atlas chain located at 1150 m asl on Mount of Guezoul and the Massif of Saida and Frenda at 1200 m asl. The study area also covers the mounts of Nadhor on the edge of the steppe plains of Ain Deheb and the Eastern zone of Chott Chergui to the south. In general, the relief is very heterogeneous including a mountainous area to the north, high plains in the center and semi-arid areas and steppe to the south. This significant natural potential includes more than 1,600.000 ha of agricultural lands dominated by the culture of cereal and fruit trees, 142.422 ha of forest area characterized by a rugged and wooded relief covered mainly by holm oaks and Aleppo pines, and 143.000 ha of steppes dominated by the typical formation of Stipa tenacissima L., Artemisia herba-alba Asso, Atriplex halimus L. and the associated vegetation. The variety of relief implies as well a very heterogeneous soil types which are characterized in general by the presence of lime accumulation, low content of organic matter and high sensitivity to erosion and degradation (Achir, 2016).
The climate is semiarid typically Mediterranean characterized by a harsh cold winter and hot and dry summer. Climatic data recorded from 1986 to 2018 indicated that annual rainfall ranges from 200 to 400 mm per year with a seasonal fluctuation ranging from 157 mm in winter to 31 mm in summer with an average temperature of 37.2°C. The warmest months are from Jun to September, while the coldest months are from November to March (Taïbi, 2009).
The health sector of the region is composed of five public hospital establishments, three specialized hospital establishments along with many proximities to public health establishments for an estimated population of 1,007.635 inhabitants. According to the epidemiological assessment launched in 2017, this region had a high rate (21.1%) of deaths caused by different diseases (mainly cardiovascular diseases, cancer, chronic respiratory diseases, chronic kidney diseases and diabetes among others). This may be due to several factors such as the significant deficit in specialist doctors, the lack of equipment, the poverty of the populations, the difficulty of access to medications among others which have led unfortunately to a remarkable deterioration of people health in the region. Historically, the region of Tiaret was an important political and economic center in the northwest of Algeria and constitutes a crossroads of several civilizations namely Ziride, Hammadite, Abdelwadid, Rostemide, Ottoman Empire and French colonization (Kouzmine et al., 2009). In addition to its location as a connection city between east and west regions of the country, Tiaret region is also considered as the Saharan gate which ensures the connection and the passage of travelers from the north to the south regions of Algeria. The historical view and geographical location make the region of Tiaret a place of diffusion and center of transfer of a great traditional knowledge. Local population works mainly in agriculture (animal farming, pastoralism and plant farming), commercial sector and service industries. Socio-demographic characteristics of the informants are exposed in Table 1.

Data collection
The present ethnopharmacological study was conducted through field studies achieved from December 2018 to May 2020 to list the most medicinal plants used for the treatment of various diseases in the region of Tiaret, North West of Algeria.
In total, sixty-four herbalists and traditional practitioners interviewed throughout this study (n=64). This study is directed in agreement with the requirements of the declarations of Helsinki and was approved by the scientific committee (PVCSF/FSNV/27 Nov 2018) for ethical criterion in the faculty of Natural and Life Sciences, Ibn Khaldoun University of Tiaret (Algeria). Hence, semi-structured interviews based on note-taking while interviewing were conducted with the local dialect and were generally took place in public spaces in collecting the ethnopharmacological data as described by Martin (1995).
Informant consent was obtained through oral agreement prior to the interviews to authorize the collection, use and publication of data, then informants were asked to list aromatic and medicinal plants used for the treatment of various ailments and were requested to provide detailed information about their uses .
Interviews covered popular and vernacular names of the used species, parts used, mode of preparation and administration, dosage, period of treatment and toxicity or side effects among other information. Local names were provided mostly in Arabic language and informants were asked whether they would be willing to deliver a sample or to recognize it in photos if the material was not available. The collected specimens were pressed and dried on site then the voucher specimens were identified by specialists and conserved in the laboratory at the Faculty of Natural and Life Sciences, University of Tiaret (Algeria). The identity of plant species was verified according to the available bibliographical resources and scientific names were confirmed in accordance with the International Index of Plant Name (http://www.ipni.org) and the Plant List database (http://www.theplantlist.org).

Data analysis
The obtained ethnopharmacological data were assigned into various ailments categories which have been reported by informants. The use report (UR) was assessed by calculating the total uses for the plant species by all informants within each use-category for that plant (Prance et al., 1987).
The Frequency of Citation (FC) is calculated as the sum of informants that cite a use for the plant species (Prance et al., 1987).
The use value (UV) is a quantitative method that can be used in order to prove the relative importance of the plant species known locally. It was calculated following the adaptation of da Silva et al. (2014) using the following formula: where UV is the use value of the plant species p mentioned by the informant i; ΣUR ip is the number of uses reports of the plant species s mentioned in each event by the informant i; n ip is the number of events in which the informant i cited the plant species p.
The homogeneity on the informants' knowledge was evaluated by calculating the Informants' Consensus Factor (F IC ) (Andrade-Cetto & Heinrich, 2011) using the formula: where N ur is the number of use reports for a particular ailment category and N t is the number of species cited for the same ailment by all informants. The values of the index range between 0 and 1, where values close to '1' indicate the highest level of consensus.
All the statistical analyses were performed using the computing environment R (R Development Core Team, 2013). Continuous data were represented as mean ± standard deviation while frequencies and percentages were calculated for categorical variables.

Sociodemographic features
In the present study, the number of men herbalists was higher than that of women (60 men versus 4 women). The observed gender bias might be due to the cultural traditions and structure of the society, where work outside the family, such as this kind of activity, is not allowed for women. Overall, the age group of 30-45 years-old is the most frequent amongst the herbalists involved in this study (45%). However, the age group over 60 yearsold is less represented (about 11%). Besides, most of the herbalists have secondary (42%) or middle (33%) institutional level while around 9% were illiterate. Nevertheless, only 4 herbalists (6%) are undergraduate or graduate from the university. This could be explained by the fact that the majority of herbalists belongs to rural poor regions where the access to school and university is not usually allowed.
Almost all the interrogated herbalists have acquired their knowledge from other persons, and they refer mainly to the experiences of their ascendants or of other traditional healers to use medicinal plants as remedies. It should be noted that older herbalists, mainly illiterates, have shared more knowledge about the diversity and uses of medicinal plants. This is due certainly to vast experience accumulated along times and transmitted from generation to generation throughout practices especially where no other alternative was available. In fact, the transmission of this valuable ethnomedicinal knowledge is presently in danger of loss especially that the new modern generations have changed their lifestyle and habitudes and tend to not believe too much of using plants as remedies (Bouasla & Bouasla, 2017;Sargin et al., 2015).

Plant parts used
Leaves were the most frequent used plant part (27%), followed by aerial parts (23%), seeds (15%), roots (9%), flowers (7%), and fruits (6%). However, the use of stems, barks, tubers, rhizomes and bulbs was less frequent and was cited less than 5% each ( Figure 3). It should be noted that phytochemical compounds differ in quantity and quality according to the plant part in which they are accumulated. The interrogated herbalists throughout the present study are not fully aware of this aspect but they use the different plant parts according to traditional heritage rather than a scientific basis. Most of ethnobotanical studies have reported the frequent use of leaves in herbal remedies (Adnan et al., 2014;Sher et al., 2015). Leaves are very useful for plants identification, very abundant, easily accessible to local populations and rich with bioactive compounds derived from photosynthesis (Bouasla & Bouasla, 2017;Sargin et al., 2015). Besides, the use of leaves is better for the survival of plants as the use of whole plant or roots can seriously threaten the local flora (Umair et al., 2017).

Modes of preparation and administration
Most of plants are used as infusion (47%), decoction (28%) or even powdered (10%) to be ingested or used in other mixtures and preparations. However, some plant parts are eaten raw (6%) or used for inhalation (2%) and maceration (1%) (Figure 4). The mentioned methods of preparation could be suitable for some plants but not for the others. In fact, the boiling procedure can cause severe degradation of the therapeutic components in some medicinal plants. In addition, the suitable dosage required to reach the expected benefits could not be acknowledged with precision since it was dissimilar among informants interrogated throughout this study. This concern has been raised also by several researchers indicating that the fixed doses to be administered by patients in traditional medicine is still not yet well-defined (Jaradat et al., 2016). Therefore, further studies are needed to determine the concentration of active ingredients with respect to their method of preparation.
Herbalists prescribed most of their preparations through oral administration (91%) followed by topical application (7%) and nasal and gargling (1% each). These findings agree with those of Ahmad et al. (2014), Rashid et al. (2015). Oral and topical modes of administration permit rapid physiological action to promote healing power (Rehman et al., 2015).
Herbalists advised the use of mixtures based on several plant species with other ingredients such as honey, olive oil, goat milk and butter, water, yogurt, couscous, eggs, etc. to improve the taste and enhance the therapeutic effects. Mixtures of various species might have positive synergic effects and attenuate the adverse effects or toxicity of some plants of the mixture (Ait Abderrahim et al., 2019a, b, c).

Categories of diseases and therapeutic indications
The ethnomedicinal plants reported throughout this study were used to treat 68 different ailments classified into 13 categories; digestive (52 species), circulatory (39 species), respiratory (37 species), urogenital (33 species), glandular (29 species), neurological and psychological (28 species), dermatological (27 species), osteoarticular (25 species), cancer (15 species), ocular (10 species), mouth (8 species), general ailments (21 species) and others (7 species) ( Figure 5). The obtained results indicated that 31% of the reported plant species are recommended for the treatment of digestive diseases. However, 16% of the plant species are used to treat respiratory diseases. Nevertheless, the management of circulatory system, skin alterations and nervous diseases was secured by 10% of the inventoried plant taxa for each ailment. The remaining 23% of the cited species are used for the treatment of a wide range of diseases such as urinary ailments and metabolic disorders including diabetes and cancer (Figure 4). These findings are in accordance with previous studies carried out in Algeria and in the Mediterranean region. Most of medicinal plants listed by Boudjelal et al. (2013) in the region of M'Sila (north east of Algeria) were recommended to treat digestive problems, diabetes, blood pressure and cancers. In addition, Ouelbani et al. (2016) have reported the use of medicinal plants mainly for the treatment of gastrointestinal disorders in the region of Constantine and Mila (north east of Algeria). Similar findings were reported by González-Tejero et al. (2008) and Slimani et al. (2016) in the Mediterranean region.
The use of the perennial halophyte shrub Atriplex halimus is reported for the treatment of cancer, inflammatory diseases and hypertension. Benhammou et al. (2009) have reported its use to treat diabetes and internal parasites while Lakhdari et al. (2016) have noted its use for the management of gastrointestinal, cardiovascular, inflammatory and respiratory diseases besides diabetes and fall of placentae. This species is rich in tannins, flavonoids (flavone, flavanone, flavonols and isoflavone glycosides), saponins, alkaloids, resins, naringin, and naringenin 7-O-glucoside (Benhammou et al., 2009;Emam, 2011). The previous studies of Kabbash & Shoeib (2012) and Al-Senosy et al. (2018) have demonstrated its antioxidant, antimicrobial, antileishmanial, anti-inflammatory, antiproliferative and antidiabetic effects.
Furthermore, Bunium incrassatum is indicated to treat allergy, asthma, cough, cysts, tonsillitis and thyroid disorders. According to Benarba et al. (2015), this species is used in the treatment of allergy, bronchitis and cough. The powder of dried tubers of this species was used for bronchitis, cough, inflammatory hemorrhoids and as astringent and anti-diarrheal agent (Bousetla et al., 2015). The phytochemical analyses have demonstrated its richness in several active compounds such as scopoletin, coumarins, scoparone, β-sitosterol, caryophyllene, germacrene and farnesene (Bousetla et al., 2014;Bousetla et al., 2015;El Kolli et al., 2017). In addition, the tested activity of its essential oil has shown antioxidant, anti-hemolytic, antiinflammatory, antibacterial and antimicrobial properties (Bousetla et al., 2014;El Kolli et al., 2017).
All plant parts of Foeniculum vulgare are used for the treatment of digestive, reproductive, respiratory and endocrine disorders. In general, this plant constitutes a common remedy for gastrointestinal disorders including bloating, indigestion (Kaur & Arora, 2009). Ouelbani et al. (2016) stated that it is used in the treatment of rheumatism, muscular problems, lactation, weight loss as it possesses an antispasmodic activity. Its seeds are known to improve the unpleasant odor of the mouth (Badgujar et al., 2014). They are consumed either raw or as a tea made by adding boiling water to a teaspoon of seeds. Its extracts are also useful in the treatment of hypertension and glaucoma (Rather et al., 2016). This plant is a rich source of polyphenols, flavonoids, terpenoids, carotenoids, coumarins, curcumin, fenchone, estragole, phenolic glycosides and trans-anethole (Rather et al., 2016;Zellagui et al., 2011).
As well, Rubia tinctorum is reported in this study to treat anemia. Baghalian et al. (2010) have cited that its roots are useful for the treatment of kidney and bladder stones due to the presence of 1-hydroxyanthraquinone which is a laxative and sedative agent. In addition, Esalat Nejad & Esalat Nejad (2013) have indicated it to treat urinary diseases and menstruation pain. This plant is also indicated against cancer, inflammation, tuberculosis, wounds, rheumatism and metrorrhagia (Nejat et al., 2017). Ford et al. (2015) and Nejat et al. (2017) have attributed the biological properties of this species mainly to the anthraquinones along with other bioactive phytochemical compounds such as polyphenols, flavonoids, alkaloids, terpenes, tannins, cardiac glycosides, coumarins and iridoid asperuloside.
However, many species has been reported just once such as Thapsia garganica, Vicia faba, Tilia cordata and Ricinus communis which may translate the lack of knowledge about their uses and their beneficial effects.

New therapeutic uses and new ethnomedicinal plant species
In general, 246 new therapeutic uses of 55 known medicinal plant species belonging to 29 botanical families have been reported for the first time in the north Africa throughout the present study (Appendix 1). These species are belonging mainly to Apiaceae (8 species), Asteraceae (8 species), Lamiaceae (7 species), Fabaceae (5 species) and Rosaceae (4 species) families. These findings consolidate the importance of the cited botanical families as effective source of bioactive molecules holding potential therapeutic effects Meddour & Meddour-Sahar, 2016;Sarri et al., 2014Sarri et al., , 2015.
Moreover, five plant species have not been previously reported as medicinal plants in the north Africa and Algeria namely Bunium incrassatum, Echinops spinosissimus, Cucurbita moschata, Pennisetum glaucum and Malus domestica.
Interestingly, Bunium incrassatum was used to treat asthma, cysts, thyroid disorders and tonsillitis. However, Echinops spinosissimus was indicated for cough, influenza, inflammation and it is widely used to clean the female genital apparatus after childbirth. In addition, Cucurbita moschata was indicated for renal lithiasis while Pennisetum glaucum was recommended for anorexia, breastfeeding and osteoarthritis. Besides, Malus domestica was used to normalize cholesterol and high blood pressure.

Endemic, rare and endangered plants species
Among the 107 medicinal plants species reported throughout this study, 6 species are endemic to North Africa-Algeria, Northern and Central Sahara i.e. Pistacia atlantica, Tetraclinis articulata, Oudneya africana, Euphorbia guyoniana, Teucrium polium and Marrubium deserti. Furthermore, six species are considered threatened, rare or endangered i.e. Artemisia herba-alba, Anacyclus pyrethrum, Cuminum cyminum, Saussurea costus, Boswellia sacra and Pistacia atlantica. In addition, 7 species are listed as uncultivated plant species protected by the Algerian law (executive decree corresponding to January 2012) i.e. Pistacia atlantica, Oudneya africana, Teucrium polium, Juniperus oxycedrus, Juniperus phoenicea and Tetraclinis articulata. Unfortunately, the intensive use of rare and threatened plant species by the local population might lead to the loss of these genetic resources and consequently to their extinction.
These results corroborate the previous findings of Benarba et al. (2014), Ouelbani et al. (2016) and Eddouks et al. (2017) which demonstrated also higher use values for Trigonella foenum-graecum and Nigella sativa. The traditional indication of N. sativa to treat anemia and inflammation has been proven and attributed mainly to its thymoquinone and nigellone molecules which can act as inhibitors of the generation of eicosanoids, leukotrienes, and histamine (Al-Saleh et al., 2006;Tayman et al., 2013). As well, the antioxidant activity of N. sativa was also determined (Bouasla et al., 2014). In addition, T. foenum-graecum has also a long history of use in the treatment of respiratory infections, reproductive disorders, treating hormonal disorders, increasing milk supply, and reducing menstrual pain and reduce fever. This species has been shown to possess antiviral, antimicrobial, hypotensive, antioxidant, anti-inflammatory, hypoglycemic, hypolipidemic and antitumor activity (Al-Oqail et al., 2013). (2017) (Neves et al., 2009) and Italy (Idolo et al., 2010) to treat different respiratory ailments such as bronchitis, allergy, cold, flu and cough. Thymus spp. are rich in several active compounds mainly in thymol, carvacrol, p-cymene, eugenol, and luteolin that may explain its remedial potential (Monira & Naima, 2012). These compounds are known to have antiviral, anti-inflammatory, antioxidant, anti-nociceptive, antianaphylactic and antibacterial properties (Javed et al., 2013).

Informant consensus factor
The documented use reports data have been classified into different ailment categories. The informant consensus factor (FIC) was calculated for each ailment category to select the categories of diseases for which the species are traditionally used, and the range was from 0.54 to 0.81 (Table 4). The highest F IC value (0.81) was reported for digestive diseases with 52 used plant species and 274 reported uses, followed by cardiovascular and urogenital diseases (0.73 each). The higher values of the index indicate higher homogeneity of knowledge among informants. Similar results have been reported by Benarba et al. (2015) in Mascara (northwest of Algeria), Bouasla & Bouasla (2017) in Skikda (northeast of Algeria), Fakchich & Elachouri (2014) in Morocco and Tuttolomondo et al. (2014) in Italy. The high F IC value of digestive diseases may be explained by its high incidence in the region from apart, and the ability of the traditional healers to easily diagnose these pathologies from another part (Punnam Chander et al., 2014). The high incidence of digestive disorders might inform probably an unhealthy lifestyle. Interestingly, cancer is reported to have the 5 th highest F IC value (0.66) which could be attributed mainly to the high incidence of cancers in the region.  It should be noted that Pistacia atlantica, Tetraclinis articulata, Oudneya africana, Euphorbia guyoniana, Teucrium polium and Marrubium deserti are endemic to North Africa-Algeria, Northern and Central Sahara. Furthermore, Artemisia herba-alba, Anacyclus pyrethrum, Cuminum cyminum, Saussurea costus, Boswellia sacra and Pistacia atlantica are considered threatened, rare or endangered species. Therefore, an urgent intervention is required to protect these genetic resources from the abusive use by local population which might lead to their loss and extinction.
Evidently, it is the time to increase effective scientific studies on the determination of the nature and mechanisms of action of bioactive compounds included in these medicinal plants in order to produce effective and safe drugs.