The use of plants in the traditional treatment of diabetes patients: The use of plants in the traditional treatment of diabetes patients: The use of plants in the traditional treatment of diabetes patients: The use of plants in the traditional treatment of diabetes patients: survey in southern survey in southern survey in southern survey in southern MoroccoMoroccoMoroccoMorocco

This study was conducted in public healthcare establishments in Guelmim city in south of Morocco to report medicinal plants used in folk medicine to treat diabetes. Three hundred sixty-two informants were interviewed through semi structured interviews. The inventory includes scientific, popular and common names of the plants, used parts and method of preparation. The survey shows that 24.6% of the patients use these plants. Twenty-seven medicinal plants belonging to seventeen families were inventoried and three species were cited for the first time in the treatment of diabetes in Morocco. Olea europea L., Artemisia herba-alba Asso and Trigonella foenum-graecum L. are the most plant species used to treat diabetes, and the two most cited families are Lamiaceae (5 species) and Apiaceae (4 species). Leaves represented the most utilized part of plants and decoction was the most cited mode of preparation of drugs. The present study highlights the wide variety of herbal remedies used to treat diabetes and the frequency of this use in diabetic patients.


Introduction Introduction Introduction Introduction
Diabetes is a serious chronic and metabolic disease that occurs when the pancreas does not produce enough insulin or when the body cannot effectively use the insulin it produces (WHO, 2016). The disease is characterized by elevated levels of blood glucose, which leads over time to serious damage to the heart, blood vessels, eyes, kidneys and nerves (WHO, 2016). According to Shaw et al. (2010), the world prevalence of diabetes among adults (aged 20-79 years) will increase to 7.7% by 2030, total number of people with diabetes is projected to rise from 285 million adults, in 2010 to 439 million adults by 2030, and number of adults with diabetes expected to increase 69% by 2030 in developing countries, compared to 20% for developed countries.
2 In Morocco, a country in the midst of a demographic, nutritional, social and epidemiological transition (Benjelloun, 2002), diabetes has significantly high frequency, with more than one and half million types 2 diabetics in 2010, and would reach 2.5 million by 2030 (Shaw et al., 2010). Despite the development of modern medicine, it is still difficult to achieve adequate glycaemic control in many diabetic patients due to the gradual decline in β cell function (Wallace and Matthews, 2000). All existing therapies for the treatment of diabetes, however, have limited efficacy and / or significant side effects (Moller, 2001;Rotenstein et al., 2012). The use of drugs and their side effects are of great concern, and most patients have perceived negative side effects of conventional medicine (Ithnain et al., 2020). In addition, there is also the need for chronic intake of a large number of drugs for diabetic complications (an average of four per day for each patient) (Enwere et al., 2006). Therefore, patients often resort to alternative treatments such as herbal remedies.
Traditional medicine based on the use of medicinal plants for the treatment of many diseases, including diabetes, continues to be used, and in recent years its popularity has only increased. All over the world, studies have shown that many diabetic patients use herbal medicine (Patel et al., 2012;Ezuruike and Prieto, 2014;Kamel et al., 2017;Hamza et al., 2019). Several pharmacological studies have also demonstrated the hypoglycaemic effect of plant extracts justifying their use in traditional medicine, this is for example the case of seeds of Trigonella foenum-graecum L. (Mowl et al., 2009) or leaves of Phoenix dactylifera (Mard et al., 2010).
Several studies have been carried out to describe the use of herbal medicine by people with diabetes in Morocco (Ziyyat et al., 1997;Jouad et al., 2001;Tahraoui et al., 2007;Katiri et al., 2017). So far, there is no data on the use of plants for the treatments of diabetes in the city of Guelmim. The Province of Guelmim is part of the Guelmim-Oued Noun Region and covers an area of 10,783 km , or 18% of the territory of the region. It is limited to the north by the Tiznit and Ifni Provinces, to the south by the Tan-Tan and Assa-Zag Provinces, to the east by the Tata and Assa-Zag Provinces and to the west by the Atlantic Ocean (figure 1). The Guelmim province constitutes a buffer zone between the Moroccan Sahara and the Souss plain. The proximity to the Atlantic Ocean mitigates the effect of Saharan continentality for the part close to the ocean.
Thus, the aim of this study was to identify the medicinal plants used to treat diabetes by people in public healthcare establishments in Guelmim city.

Presentation of the study area
This study was carried out in seven structures of primary health care establishments made up of seven urban health centers 1st level of the city of Guelmim (Figure 1).

Methodology
The study was conducted from February until June 2019 at health centers in Guelmim where 362 diabetic patients were interviewed. All registered diabetics more than age 18 and above and a minimum followup of three months at health centers, Guelmim, were eligible for the study.
The data were collected through semi-structured interviews, and subsequently codified and categorized for proper statistical analysis. Interviews were carried according to a three-part questionnaire. The first part includes the profile of the interviewed diabetics (sex, age, family situation, level of study, professional activity and medical background). The second part contains diabetes-related characteristics (type of diabetes, diabetes treatment, medical follow-up), while the third part concerns plants and their uses (reasons for using medicinal plants, vernacular names, mode of preparation and administration and the duration of administration, part used, results of phytotherapy, effects of the drugs used).
Access to information on people with diabetes was obtained following an authorization from the regional health directorate of Guelmim. All participants were made aware that this study is for research purposes and their participation was voluntary. The patient's consent was obtained before each interview with courteous information regarding the objectives and the nature of the work. The survey respondents have been identified by an anonymous study number corresponding to each of them and information on all participants is kept confidential.
At first, a list of vernacular names of medicinal plants used by this population was created. These plants were identified according to flora of Morocco (Fennane et al., 2007;. Scientific names of plant species were determined according to the Plant List (http://www.theplantlist.org).

Data analysis
The data reported on the questionnaire were entered and listed on a Microsoft Excel database and Statistical Packages for Social Sciences (SPSS) version 24.0 and analysed to determine the proportions of di erent variables, the statistical significance was set at p < 0.05. Medicinal plants inventoried in this study were organized in alphabetical order by family. The data reported concerned family, scienti c name, local name, part used, the utilized method, route of administration, and duration of treatment. These results were analysed using speci c quantitative parameters.
In addition, ethnobotanical data was analysed using relative frequency of citation (RFC) to determine the well-known and most used species among diabetic patients. The relative frequency of citation (RFC) shows the local importance of each species and it's obtained by dividing the number of informants mentioning a useful species frequency of citation (FC) by the total number of informants in the survey (N) (Tardío and Pardo-de-Santayana, 2008). This index was calculated by the following formula: RFC = FC/N (0 < RFC < 1).

Results Results Results
Socio-demographic characteristics of respondents are shown in Table 1. During our survey, we interviewed 362 diabetic patients from which 60.22% were female and 67.4 were married. The diabetic patients were arbitrarily divided into four age groups: < 38 years, 38-52 years, 53-67 years and > 67 years. Average age is 52.54 ± 15.45 years, and about 80 percent are aged 38 and over. For the educational level, over half of the participants (59.67%) had never been to school and only 7.18% of patients had attended a higher education institution. Among the diabetic patients of the survey, 41.71% had type 1 diabetes, 56.63% had type 2 diabetes and 1.66% had gestational diabetes. They managed their disease in 53.31% with oral hypoglycaemic and in 38.95% with insulin. In this study, 24.6% (55 women and 34 men) of the respondents used herbal medicine to treat their diabetes ( Table 1) and 83% of these users consumed herbal and prescribed medicines concurrently ( Figure 2). Response by the users showed that experience of others (54%) were the main sources of information on the use of herbal medicine ( Figure 3).     Table 4). The families with most antidiabetic plants included Lamiaceae (5 species) and Apiaceae (4 species) (Table 4). It was also found that Olea europaea L. (22.6%), Artemisia herba-alba Asso (16.7%) and Trigonella foenumgraecum L. (9.5%) were frequently used by diabetics ( Figure 4). From the twenty-seven plant species inventoried, eight were used for diabetes type 1 only, ten plants were used for diabetes type 2 only, and nine plants were used both for type 1 and type 2 diabetes (Table 5) Table 4).
The most used organ parts in present study were leaves (33.7%), seeds (25.8%) and leafy stems (21.3%) ( Figure 5). Diabetic patients used different preparation modes such as decoction, infusion or maceration ( Figure 6). The most common mode of preparation was decoction (52%). Some plants were used in more than one method of preparation. The oral route of administration (100%) was the only used route by diabetic patients who participated in this survey. The duration of treatment varied considerably from one plant to another and for the same plant. The most common treatment duration was one week (48.31%) followed by one month (32.58%), and lifelong treatment (16.85%).
As a result of treatment, over sixty percent of the patients stated there is an improvement and 25.8% stated they were not (Table 2). Moreover, one or more side effects concurrent with use of medicinal plants were 6 observed in 17 patients (19%). Thirteen respondents presented gastrointestinal disorders (Gastritis, vomiting, constipation, diarrhea, Epigastralgia…) and three cases presented hypoglycaemia (Table 3).      Table 3. Table 3. Table 3.  Our survey was conducted at health centers in Guelmim City and included 362 diabetic patients. Results revealed that patients with diabetes frequently use medicinal plants to control the disease. Indeed, 24.6% of the respondents used herbal medicine to treat their diabetes and 83% consumed medicinal plants in association with pharmaceutical drugs. This was in accordance with several studies, which reported the interest of diabetic patients in medicinal plants to treat their diabetes in Morocco (Eddouks et al., 2002;Tahraoui et al., 2007;Skalli et al., 2019 ;Alami et al., 2015;Laadim et al., 2017 ;Barkaoui et al., 2017;Katiri et al., 2017;Mrabti et al., 2019;Chetoui et al., 2021) and in other countries (Bell et al., 2006;Otoom et al., 2006;Inanç et al., 2007;Khalaf and Whitford, 2010;Ali-Shtayeh et al., 2012;Ching et al., 2013;Kamel et al., 2017;Mekuria et al., 2018).
Sociodemographic data indicated that more than 80% of diabetic patients who used medicinal plants are aged 38 years and above. Our results are in line with the previous studies conducted in other regions of Morocco (Jouad et al., 2001;Skalli et al., 2019;Barkaoui et al., 2017). According to Skalli et al. (2019), older diabetic patients have acquired valuable experience during their life as users of medicinal plants or have learned from the experiences of others.
The distribution by sex showed that women (61.8%) used herbal medicine more often than men, although this is not statistically significant (p= 0.05). In comparison with other Moroccan regions, the more frequent users of plants were women with the respective percentages of 81% (Skalli et al., 2019), 74.5% (Chetoui et al., 2021) and 58.5% (Alami et al., 2015). Similar findings were also reported in elsewhere in the world (Ogbera et al., 2010;Amaeze et al., 2018).
This study showed that illiterate diabetic patients seem to be the more frequent users (59.67 %) of plants for diabetes. This is consistent with findings in other studies (Chetoui et al., 2021;Laadim et al., 2017;Alami et al., 2015;Kpodar et al., 2015;Kadir et al., 2012;Jouad et al., 2001). Contrary, Kumar et al. (2006) in India, Kamel et al. (2017) in Saudi Arabia and Amaeze et al. (2018) in Nigeria indicated that the educational level positively influenced herbal medicine use.
The current study emphasized that the rate of herbal medicine use was high among participants managing their disease with oral hypoglycemic (44.9%) and among those using insulin (43.8%). Previous studies conducted in the Beni Mellal-Khenifra region (Chetoui et al., 2021) and Oriental Morocco (Alami et al., 2015) showed that the rate of herbal medicine use was high among patients taking oral medications alone or treated by both oral hypoglycaemic agents and insulin injection. Patients use herbal medicine to reduce their daily insulin dose (Chetoui et al., 2021) or to potentiate the anti-diabetic activity of the allopathic treatment and thus contribute to the management of their disease (Alami et al., 2015).
This study also found that 83% of the respondents consumed herbal and prescribed medicines concurrently; same comportment has been reported amongst diabetic patients in other studies. Thus, Alami et al. (2015) showed in oriental Morocco a significant result of using herbal medicine alongside allopathic treatment among patients treated by both oral hypoglycaemic agents and insulin injection. In Rabat, Skalli et al. (2019) reported that 53.6% of the patients' used plants in combination with their conventional treatment. Amaeze et al. (2018) in Nigeria indicated that 35.4% of the respondent's consumed herbal in addition with prescribed medicines. According to Suroowan et al. (2021), herbal and conventional medicine combination is a potentially dangerous practice leading to perilous Herbal drug interactions and toxicity. In addition, Chelghoum et al. (2021) revealed, through several clinical trials, that the anti-diabetic plants had a synergistic effect with oral anti-diabetic agents, which can increase the hypoglycemia of diabetics.
The most used plant families in this study were Lamiaceae, Apiaceae and Asteraceae. This has been confirmed by other studies conducted in different areas of Morocco (Chetoui et al., 2021;Idm'hand et al., 2020;Skalli et al., 2019;Laadim et al., 2017;Katiri et al., 2017;Barkaoui et al., 2017) where diabetic patients mostly use plants belonging to these three families. The richness of Morocco flora by species belonging to these families might explain this wide use. In this study, 27 species were identified and most of them have been validated experimentally in previous research for their hypoglycemic activity (Guex et al., 2019;Boudjelal et al., 2015;Al-Khazraji et al., 1993).
The comparison with previously literature conducted in different regions of Morocco showed that Saussurea costus (Falc.) Lipsch., Aquilaria malaccensis Lam. and Nardostachys grandiflora were mentioned for the first time in Morocco as hypoglycemic plants. These three plants are known for their medicinal uses and are used in many countries for the treatment of various ailments. Saussurea costus (Falc.) Lipsch. is recommended for rheumatism, abdominal pain, anorexia, nausea (Choi et al., 2012) for colds and join paint (Rani and Rana, 2014) for asthma, inflammatory diseases, ulcers and stomach problems (Pandey et al., 2007).
Nardostachys jatamansi (D. Don) DC. has been reported to have many therapeutic activities like antifungal, antimicrobial, antioxidant, hepatoprotective and cardio protective properties. It is used in the treatment of insomnia and CNS disorders. The vasodilator, bronchodilator, spasmolytic and platelet aggregation inhibition activities of the plant have also been reported (Sahu et al., 2016).
Relative RFC values obtained from the reported species indicate the degree of indigenous knowledge shared by local people regarding the use of medicinal plants for the treatment of diabetes. The plants having the highest RFC are, in fact, predominantly used and commonly known by the local people. These may prove important for linking and evaluating research for future drug discovery and sustainable use of medicinal plants for the treatment of diabetes.
In our study, plant leaves were the most used plant part by the patients. This could be explained by the availability of leaves as the main photosynthetic organs throughout the year (Yetein et al., 2013) and their richness in therapeutic substances (Skalli et al., 2019;Yetein et al., 2013). The preference for leaves may be linked also to the fact that use of leaves is less damaging to the plant species compared to the use of entire plant or other parts (Zheng and Xing, 2009). This predominance of plant leaves had also been recorded in several studies (Chetoui et al., 2021;Skalli et al., 2019;Barkaoui et al., 2017;Katiri et al., 2017;Gnagne et al., 2017;Kadir et al., 2012), which confirmed the effectiveness and importance of the use of this plant part worldwide.
Regarding the plants noted in our survey, the most common method of preparation used by the patients is decoction. The dominance of this mode of preparation has also been reported by other studies (Chetoui et al., 2021;Barkaoui et al., 2017;Eddouks et al., 2017;Katiri et al., 2017;Gnagne et al., 2017;Hachi et al., 2016;Orch et al., 2015). These results were in disagreement with other works performed in Rabat (Skalli et al., 2019), which showed that the infusion is the most requested mode. The use of decoction to treat diseases might be explained by the fact that the decoction allows collecting the most active substances and reduces or cancels the toxic effect of certain recipes (Salhi et al., 2010).

12
The plants were mostly consumed by oral way which might be due to easy administration of this mode (Skalli et al., 2019) or can be explained by the fact that this pathology is linked to deep organs. This is consistent with the results of others studies (Skalli et al., 2019;Gnagne et al., 2017). The duration of treatment varied considerably from one day to lifelong treatment. Skalli et al., (2019) have also noted this variation. Lifelong use of plants with conventional treatment testifies patient trust in herbal medicine (Skalli et al., 2019). Additionally, Jouad et al. (2001) reported that patients did not take into account the accumulation of certain constituents in the body after prolonged use of plants, which could cause serious side effects.

Conclusions Conclusions Conclusions Conclusions
This study is the first one on the use of medicinal plants in diabetic patients in the city of Guelmim (Morocco). The findings of the present investigation indicated a low utilization of herbal medicine to treat diabetes in comparison of others areas in Morocco. Over a three quarter of the diabetic patients used herbal medicine alongside allopathic treatment, thus increasing the potential for herb-drug interactions and consequently, therapy failure. The present study highlights the wide variety of herbal remedies used to treat diabetes and the frequency of this use in diabetic patients. In addition, and to our knowledge, three plants (Saussurea costus (Falc.) Lipsch., Aquilaria malaccensis Lam. and Nardostachys jatamansi (D. Don) DC.) were reported for the rst time to treat diabetes in Morocco and more of five plants were used in the traditional treatment of diabetes has been proven toxic by several scientific research. Consequently, these results on the medicinal plants used in Guelmim constitute a database for future studies to experimentally assess the potential of these plants. Despite