Ethnobotanical Survey of Medicinal Plants Used by Traditional Healers to Treat Diabetes in the Taza Region of Morocco

Type 2 diabetes is one of the noncommunicable diseases that is becoming a pandemic in Africa. In Morocco, traditional healers have started to use herbal medicines for the treatment of diabetes either individually or in combination with food. The current study aimed to perform an ethnobiological survey of antidiabetic plants use in the Taza region of Morocco. A total of 193 traditional healers were interviewed using a semistructured questionnaire. Data collected were analyzed utilizing the use value (UV), fidelity level (FL), and relative frequency citation (RFC) indices. Forty-six plant species belonging to 28 families were recorded for the treatment of diabetes in the Taza region of Morocco. The most frequently cited plant species are Salvia officinalis, Marrubium vulgare, and Ajuga iva. Lamiaceae, Asteraceae, and Fabaceae were the most reported families. Leaves are the most used part of plants to prepare drugs, the decoction is the preferred mode of preparation, and remedies are often administered orally. Interestingly, Cytisus battandieri, Urginea maritima, Plantago ovata, and Ziziphus jujuba were reported as new medicinal plants used to treat diabetes in the Taza region of Morocco. People in the Taza region still rely on indigenous plants for their basic healthcare needs. Further research should be carried out to validate the antidiabetic effect of the newly reported plant species. This validation can be investigated by the determination of bioactive compounds and evaluation of their in vitro and in vivo antidiabetic effects.


Introduction
Herbal medicine is an alternative or a parallel treatment in many acute and chronic diseases. It is generating renewed interest in many countries around the world, particularly in North Africa. Indeed, a large number of plants are used in traditional medicine in Morocco, including some for the treatment of diabetes [1]. Despite the presence of antidiabetic drugs known on the pharmaceutical market, herbal remedies are importantly used to treat this disease [2]. Indeed, good knowledge and authentication of medicinal species in particularly by their vernacular names can avoid the problems of their side effects and toxicities [3]. However, for millennia, herbal medicines have been a valuable source of therapeutic agents, and many of today's drugs are inspired from natural herbal plants or their derivatives [4].
Scientific research on traditional herbal remedies for diabetes can provide valuable leads for the development of alternative medicines and strategies [5,6]. Despite numerous studies carried out in Morocco to bring up rational science about the use of plants by the local populations [1,[7][8][9], there is still a need to pursue investigation in order to have a comprehensive database on medicinal plants used for diabetes management. e available literature showed several Moroccan medicinal species with antidiabetic properties [6]. Although some of these plants have a great reputation in traditional medicine, many remain to be scientifically demonstrated [10].
In Morocco, as in developing countries, the use of traditional medicine is widespread, and several herbal remedies used individually or in combination with conventional medicines are recommended to treat diabetes [8]. Indeed, recently an ethnobotanical survey was carried out in the Beni Mellal region of Morocco [11] to collect the data about the traditional herbal medicine used for diabetes treatment in this region. So far, no scientific investigation has been carried out in the Taza region. erefore, the current study aims to perform an ethnopharmacological survey on traditional knowledge of medicinal plants used to treat diabetes in the Taza region.

Study Area.
is study was conducted in the province of Taza, situated in the northeast of Morocco. It is bounded by the Rif in the North, the Middle Atlas in the South, the Rharb plain in the West, and the Guercif plain in the East ( Figure 1); it constitutes the northern termination of the Middle Atlas and extends over a length of 50 km and a width of 15 km. e altitudes are between 500 and 1980 m. e temperature varies between 3.2 and 44.5°C. Although annual rainfall in this region has ranged between 84 and 120 mm over the last 8 years [12], the climate is subtropical to tropical, very dry on the coast, and wetter at altitude.

Ethnobotanical
Survey. An ethnobotanical survey was conducted from March 2019 to February 2020, and before starting the collection of ethnobotanical data, a brief explanation to the informants on the objectives of the study and the importance of the information they would provide was provided in order to obtain their consent to participate in the study. A total of 193 healers were interviewed for this purpose. e data were collected through semistructured interviews using Moroccan language (Darija). ese interviews were designed to record information about the plants used to treat diabetes mellitus and their local names, the used parts of the plant, the methods of preparation, the administration of drugs, and the demographic characteristics of the study participants.

Preservation of Plant Specimens.
e standard method was followed with a record to collect the plant materials, drying, mounting, preparation, and preservation in special glass frames; they were later identified by Pr. Latifa Doudach. ese samples of plant material were given herbarium specimen codes, and the voucher plant samples were kept in the Herbarium of the Botany Department of the Scientific Institute of Rabat, Morocco. e complete floristic list was established after the identification and verification of the samples; the identification process included the Traditional Moroccan Pharmacopeia [13], Practical Flora of Morocco [14], Moroccan Medicinal and Aromatic Plants [15], and Vascular Flora of Morocco [14] as references. e taxonomy was confirmed based on data available on the International Plant Names Index website: http://www.ipni.org/.

Data Analysis.
Medicinal plants inventoried in this study were organized in alphabetical order by family. e data reported concerned family, scientific name, local name, part used the utilized preparations, main therapeutic use, and identification code. e obtained results were analyzed using specific quantitative parameters.

Use Value (UV).
e use value (UV) demonstrates the relative importance of plants known locally in traditional medicine [16]. Use value (UV) was calculated using the following formula: where UV is the use value of species, U is the number of respondents who mentioned the use of the species, and n is the total number of respondents interviewed for a given species (herbalists and local population). e highest use recorded in inquiry reports for a given plant gives a rise to the highest UV value.

Fidelity Level (FL).
Fidelity level (FL) indicates the percentage of informants claiming the use of a certain plant species for the same major purpose [17]. e fidelity level is calculated by the following formula: where N p is the number of informants who independently indicated the use of a species for the same major ailment and N is the total number of informants who mentioned the plant for any major ailment.

Relative Frequency Citation (RFC).
e collected ethnomedicinal information was quantitatively analyzed using an index of relative frequency citation (RFC) (0 < RFC < 1): is index shows the local importance of each species, and it is given by the frequency of citation (FC, the number of informants mentioning the use of the species) divided by

Demographic Features.
is study enrolled 193 informants, including traditional healers, herbalists, and knowledgeable villagers represented by 169 women (87.56%) and 24 men (12.44%), and they were interviewed (Table 1). e results showed that women were more involved in the use of medicinal plants than men, and this could be explained by the activities of women at home. Indeed, they were responsible for drying, storing, and the preparation of the herbal remedy for maintaining the healthcare of their family. eir average age was 59.5 years with a minimum of 32 years and a maximum of 87 years. e age group  was the most represented with 46.11%. e majority of the respondents belong to the rural area (92%); and 84.45% are illiterate, 12.95% primary education, 2.07% secondary education, and 0.51% university education. Regarding the origin of their knowledge, the majority of them (96.89%) who participated in this survey acquired the traditional medical knowledge of their family members, mainly grandparents and parents, and this knowledge has not been documented.

Medicinal Plants and Floristic Analysis.
is ethnobotanical survey revealed the presence of 46 plant species, belonging to 28 families used for the treatment of diabetes by participants from the Taza region, and these species were reported along with their medicinal uses and their methods of use (Table 2). e most common medicinal plant family is Lamiaceae (6 species), Asteraceae and Fabaceae (5 species each), and Apiaceae and Myrtaceae (3 species each), respectively, whereas the other families were represented with a variable number of fewer than 2 species.

Ethnobotanical Indices.
In this study, the analysis of data collected in the field allowed us to determine forty-six (46) most commonly cited plants known to most medical informants about the treatment of diabetes disease (Table 2). e obtained data were analyzed and ordered based on the value of use (UV), level of accuracy (FL), and relative citation frequency (RFC). e values of the collected plant species ranged from 0.01 to 1.63 for UV; 8.33 to 95.34% for FL, and 0.01 to 1 for RFC, respectively. Among 46 inventoried species, ten plants species identified had high FL values (FL of ˃50%), which are Salvia officinalis, Marrubium vulgare, Trigonella foenum-graecum, Olea europaea, Artemisia herbaalba, Ajuga iva, Arbutus unedo, Euphorbia resinifera, Taraxacum officinale, and Ceratonia siliqua. Likewise, while Salvia officinalis (1.00) has the highest value of RFC followed by Marrubium vulgare (0.97) and Ajuga iva (0.94), respectively. ese positions correspond to the fact that these plants were reported by the highest number of informants and RFC directly depends on the number of informants mentioning the use of this plant (FC). As shown in Table 2, S. officinalis has the highest use value (1.63) followed by M. vulgare (1.53) and A. iva (1.46).

Comparative Analysis with the Ethnobotanical Literature.
Four medicinal plants have been mentioned for the first time to treat diabetes. Indeed, the literature reviewed showed that these plants have not been reported by other Moroccan studies. ese species include Cytisus battandieri, Urginea maritima, Plantago ovata, and Ziziphus jujuba ( Table 2).

Discussion
is study reports the medicinal plants used in the Taza region to treat diabetes. e demographic features showed that women were often at home during survey hours. Some previous studies have also shown this trend [7,8,11].     [5].
Medicinal plants diversity showed a floristic diversity. Indeed, the findings were in agreement with previous studies, where these families were the most represented in diabetes mellitus treatment in Morocco [8,44,47,64], Turkey [84], and Togo [85]. e reasons for the high degree of ethnomedicinal plants of families Lamiaceae, Asteraceae, Fabaceae, Apiaceae, and Myrtaceae in the region is their wide occurrence with several traditional uses known by the local informants [8].
e survey revealed that S. officinalis, M. vulgare, and A. iva are the most used in traditional medicine to treat diabetes in this region. Literature reports showed that several of these plants have been reported in other ethnomedical surveys for the treatment of diabetes    Evidence-Based Complementary and Alternative Medicine Evidence-Based Complementary and Alternative Medicine 9  [7,44,45,47]. e antidiabetic activity of certain plants has also been experimentally proven by in vivo or in vitro studies. ese species include A. herba-alba [21,33,34], S. officinalis [27], O. europaea [29], A. iva [35], A. unedo [63], and M. vulgare [24]. Actually, certain mentioned plants open up interesting perspectives in the search for new therapeutic means, which can thus provide credible solutions by the production of low-cost and effective drugs for the treatment of diabetes. However, the use of C. battandieri, U. maritime, P. ovate, and Z. jujube for managing diabetes has not been reported. International literature has shown P. ovate and Z. jujube have been used for diabetes in other countries like Iran [30,31,36]. e majority of these plants have been reported as medicinal plants in the treatment of other diseases. C. arvensis has been used as a disinfectant, antispasmodic, antipyretic, anti-inflammatory, antiepileptic, antimicrobial, and diuretic [37,38]. Urginea maritima was used for the treatment of cardiac failure, chronic bronchitis, asthma, and diuretic [86]. Salix alba has been used for the treatment of various ailments due to its potent antipyretic, analgesic, and anti-inflammatory properties [87].
In addition, the part of the plant most frequently used in this study was the leaves, which corresponds to previous studies that declared that the leaves are part of the plant mainly used in the treatment of diabetes in Morocco [8,11], Kenya [88], Togo [81], and Pakistan [23]. e reason for the high use of leaves can be explained by their availability and their ease of collection compared with other parts like roots, flowers, and fruits [89].
Concerning the mode of preparation, similar types of results were obtained in other studies, where decoction was the most frequent mode of preparation [11,17,25,41]. e most frequently used mode of herbal remedy administration is oral ingestion (98.30 %). Today, most of the medicines were given orally, which is in agreement with other studies [11,90,91].
A bibliometric study was carried out to identify which cited medicinal plants were already tested in vitro and in vivo for their antidiabetic effects. In vitro investigations showed that some plants were studied in vitro. Indeed, Abudunia et al. [78] have tested the in vitro antidiabetic effects of methanolic, hexane, and aqueous extracts of C. arvensis collected from the region of Khemisset. All tested extracts exhibited enzymatic inhibitory effects on α-amylase, α-glucosidase, and β-glucosidase with some variability. Indeed, methanolic extract seems to be the most effective product, in particular, against α-amylase (IC 50 � 573.37 ± 36.85 µg/mL) and α-glucosidase (IC 50 � 848.83 ± 49.93 µg/ mL). Saad et al. [35] showed that aqueous and methanolic extracts of Ajuga iva exhibited remarkable inhibition of α-amylase (IC 50 � 0.210 ± 0.003 and IC 50 � 0.180 ± 0.005 µg/ mL, respectively) and α-glycosidase (IC 50 � 0.172 ± 0.012 and IC 50 � 0.130 ± 0.008 µg/mL, respectively). e authors suggested that these effects are related to the phenolic compounds present in plant extracts. Moreover, the acute toxicity evaluation on rats showed that these extracts are not toxic [35]. e root aqueous extract of A. unedo has revealed significant enzyme inhibition of α-amylase and α-glucosidase [63]. e inhibitory effect was significantly important against α-glucosidase (IC 50 � 94.81 ± 5.99 mg/mL). is remarkable result led Naceiri Mrabti and collaborators to fractionate the root aqueous extract of A. unedo and to isolate the major compounds.
e results revealed the presence of catechin as the main compound, which was isolated and tested for its inhibitory effect against α-glucosidase [92]. Indeed, the inhibitory activity of α-glucosidase was increased (IC 50 � 87.55 ± 2.23 mg/mL), compared with the inhibitory activity of aqueous extract [92]. Marmouzi et al. [79] tested the methanolic extracts of leaves and fruits of Z. lotus (Rhamnaceae) showed significant inhibition of α-amylase and anti-α-glucosidase at lower concentrations Evidence-Based Complementary and Alternative Medicine with some differences between fruit and leaf extracts. Indeed, the leaf extract revealed higher inhibitory potency as antiα-amylase and anti-α-glucosidase compared with the fruit extract for which IC 50 � 20.40 ± 1.30 and IC 50 � 8.66 ± 0.62 mg/mL, respectively [79]. However, several medicinal plants cited in this survey have shown important in vivo antidiabetic effects. U. dioica aqueous extracts were tested using the oral glucose tolerance test and intravenous glucose tolerance test and showed that the administration of extract orally at 250 mg/kg decreased glycemia significantly, which indicates a significant inhibition of glucose absorption. Moreover, using oral glucose tolerance on normal and streptozotocin-induced diabetic rats has shown that the same extract decreases plasma glucose levels at 27.4% [62]. Moreover, at the same concentration, another study revealed that the antidiabetic effect was also accompanied by hypolipidemic action [65]. Calamintha officinalis is another Moroccan antidiabetic medicinal plant that belongs to Lamiaceae family. On the other hand, Eddouks et al. [70] reported that the L. sativum aerial part aqueous extract (Brassicaceae) administered orally at 20 mg/kg exhibits a potent hypoglycemic effect without affecting basal plasma insulin. However, oral and intravenous administration of the same extract at 10 mg/kg/ h in normal and STZ-induced diabetic rats caused a significant reduction of blood glucose levels in both normal and diabetic rats. erefore, this extract normalized glycemia, enhanced glycosuria, and decreased the amount of urinary TGF-β 1 in diabetic rats. ese suggest that the plant extract has a potent inhibition of renal glucose reabsorption, which reduces blood sugar [70]. Eddouks et al. [70] showed that the oral administration of C. humilis leaf aqueous extract at 10 mg/kg decreased plasma glucose levels in normal and obese-hyperglycemic-hyperlipidemic (OHH) Meriones shawi rats. Moreover, another study showed that, at the dose of 20 mg/kg, the hypoglycemia effect was also accompanied by the potent inhibition of renal glucose reabsorption [71]. However, in vitro study using short-circuit current technique revealed that the aqueous extract caused significant inhibition of the electrogenic intestinal absorption of glucose [75]. Bnouham et al. [80] studied the hypoglycemic effect of aerial part aqueous extracts of U. dioica (Urticaceae) using oral glucose tolerance test (OGTT) at a dose of 250 mg/kg in normal and alloxan-induced diabetic rats. e results showed a strong glucose-lowering effect in normal rats and no effect in alloxan-induced diabetic rats. In another work, intraperitoneal administration of aerial part aqueous extracts of this plant at a dose of 400 mg/L in the chronic treatment of streptozotocin-induced diabetic rats and 150 mg/kg in the oral glucose tolerance test caused a significant reduction of glycemia in oral glucose tolerance and plasma glucose levels [62].
e study highlighted results about antidiabetic medicinal plants as a source of antidiabetic drugs for further investigations, in particular for medicinal plants that have not been yet investigated. However, some limitations were found during this study. e first concerns the limits in the samples of traditional healers consulted because the majority of people with significant traditional knowledge refuse to provide information through the interviews. Indeed, some participants refuse to give the names of certain plants because they consider that it is a secret in itself and quickly it limits the transmission of this ancestral knowledge. e second limitation concerns the intellectual level of these traditional healers who risk passing information that is not clear enough. e number of traditional healers interviewed is also an important limitation of this study. is limit is indeed due to the low participation of traditional healers in this survey. Moreover, other difficulties related to reaching certain areas of this region because of a bad infrastructure, which justifies the reduced number of questionnaires. In addition, despite the efforts to reach some of these regions, the questionnaire has not been completed because these areas speak the Tamazight language, which we do not speak. In this sense, future work with a well-equipped research team full of linguistic skills could yield other interesting information about traditional knowledge.

Conclusion
is work has enabled us to inventory forty-six medicinal species used in traditional medicine in the treatment of diabetes, in the Province of Taza. e frequency of the use of medicinal plants is very linked to the profile of the interviewees; younger people generally ignore this know-how. Women and men have shared medicinal knowledge, with a slight difference in favor of the former in terms of the use of medicinal plants. e most widely used medicinal plants in the studied region belong to 28 families, the most popular of which are Lamiaceae, Asteraceae, and Fabaceae. In traditional medicine, the leaves mainly represent the parts of the plant used. e decoction is the galenic form most practiced by the local population whose oral route constitutes the most used route of administration. is study allowed us to appreciate and know the practices of traditional medicine in the treatment of diabetes, transmitted by the population in this region.

Data Availability
e data used to support the findings of this study are included within the article.

Additional Points
Highlights. Medicinal plants used by traditional healers to treat diabetes in the Taza region of Morocco were reported. Lamiaceae, Asteraceae, and Fabaceae were the most represented familiesSalvia officinalis L., Marrubium vulgare, and Ajuga iva are the most frequently used medicinal plants against diabetes.

Conflicts of Interest
e authors declare that they have no conflicts of interest. 12 Evidence-Based Complementary and Alternative Medicine