Ethnobotanical Survey and Identification of Potential Interactions of Plants Used in a City in Northeastern Brazil

The study of medicinal plants is currently one of the alternative sources of allopathic medicine for therapeutic purposes. Given the high consumption of medicinal plants and the risks of indiscriminate use, the objective of the study was the identification of potential plant-drug interactions in the pharmacotherapy of the Public Health System users in a Brazilian Northeastern city, from 2015 to 2017 regarding the plant species used, as well as their therapeutic properties. An ethnobotanical study was conducted with a questionnaire. For this purpose, 46 types of plants were used by the 402 interviewees, where 297 were women, with 279 adult participants, and 269 medicinal plants used. Only 199 people out of the total interviewed used some medication, of which 55 associated the use of the drug with medicinal plants. We analyzed associations between the use of 13 plants and 27 drugs, totaling 42 potential interactions. Lemon balm was the vegetal species that presented the most common interactions among the interviewees. Thus, it was possible to conclude that medicinal plants are quite used for therapeutic purposes. However, one must be cautious about its use since they can interact with drugs, reducing or potentiating their effects.


Introduction
The use of medicinal plants (MPs) has been noted since the beginning of the civilization and this practice has been passed down through generations, drawing popular taste and leading to their planting in the houses, trade in free markets and popular market, as well as their use as a medicine [1]. According to the World Health Organization, almost 80% of the worldwide population uses medicinal plants to treat minor health problems and for several patients this is often the only available health resource [2]. In Brazil, it is estimated that there are between 350,000 and 550,000 plant species, where only 55,000 are cataloged and are distributed among different regions of the country. However, some of these species do not have studies about their therapeutic potential, although this is a process that has been evolving significantly [3]. In addition, Brazil also has a long tradition of using medicinal plants linked to popular knowledge transmitted through generation [4].
Because of their pharmacological properties, the use of MPs has been encouraged by health regulatory agencies in order to develop integrative/complementary methods for resolving health problems 156 System. Brazilians are also increasingly interested in "natural" ways to promote a healthier life. Approximately 82% of the population uses medicinal herbal products [6]. For many patients, the use of a single drug is not sufficient, and when two or more drugs are prescribed, the desired benefit is not always achieved, since they may interact negatively, increasing or reducing the therapeutic effect or the toxic effect of one or the other [7]. It should be noted that these interactions do not reduce to the universe of the synthesized chemical substances, but they can occur between those present in plants used in the form of teas, homemade syrups and phytotherapics [8]. Thus, this study aims to evaluate the use of medicinal plants by patients from a community in the Northeast of

Methods
This is an ethnobotanical study with a questionnaire interview and collection of botanical material (when necessary). It was carried out in the municipality of Lagarto, comprising an area of approximately 968,921 km² situated in the southern portion of the state of Sergipe, Northeastern region of Brazil Figure 1, 78 km away from the capital, Aracaju. It presents a semi-arid transition climate dominating most of its lands on the western part of the municipality, where a local vegetative variety can be found [9]. It has about 103,188 inhabitants, with basically half of them residing in the rural area and the other half in the urban zone [10]. This research was carried out at the Maria do Carmo Nascimento Alves Health Center located in the municipality of Lagarto-SE. This unit targets 6 micro-regions comprising different neighborhoods and accompanied by 6 different community agents. Data collection was carried out in the region comprised by the Ademar de Carvalho neighborhood, which consists of 1,282 families accompanied by home visits of community health agents, in addition to consultations with physicians and nurses of the unit (Figure 1). In order to obtain the number of users to be interviewed, the sample calculation was performed considering a tolerable error of 5% (95% confidence), where after the calculation the minimum sample size was 296, but it was possible to apply the questionnaire to 406 users. For the calculation, the following equation was used: where Ip = Number of informants who suggested the use of a species for the same main objective (therapeutic use), ( ) Iu = Total number of informants who mentioned plant species for any use [2].
The identification of potential drug-plant interactions was carried out by means of a bibliographical survey of the plants used, in scientific articles indexed in national and international bases, being the bases used: Pubmed, Scielo, Lilacs, Science direct. In addition, it was consulted through the site, the Plant-Drug Interaction Observatory of the Faculty of Pharmacy of the University of Coimbra. Subsequently, interactions were classified on the pharmacodynamic or pharmacokinetic mechanism and on the risk: mild, moderate and severe. After the questionnaires were applied, the data were tabulated on the Microsoft Office Excel ® 2007 spreadsheets, submitted to descriptive statistical analysis. and gastrointestinal problems (5%). In 2000, the prevalence of arterial hypertension in the world population was 25% and the estimate for the year 2025 is 29% [12].

Results and Discussion
The increase among individuals with blood pressure matches an increasing risk factor for cardiovascular diseases [13]. to human health, provided the user has prior knowledge of its purpose, risks and benefits [15].   [17]. Besides, this tea also has anti-inflammatory and immunomodulatory properties, which aid in the treatment of various atherosclerotic, dietetic and even carcinogenic diseases [4].
Similarly, eggplant (Solanum melongena L.) has been reported to lower cholesterol. Despite this, the literature shows that a deeper understanding of this therapeutic activity is necessary since it has not been fully elucidated [18]. Another plant that was also used with divergent purposes of the literature was the elderberry  (Table 2). Fidelity levels higher than 50% are considered as reliable for use, which was observed for most plant species, showing the importance of the use of these species in the treatment of the diseases mentioned in the study area. Peumus boldus and Equisetum sp were highly utilized plants that had the highest fidelity levels of 93.12% and 87.87% in the treatment of gastrointestinal discomforts and inflammations, respectively. Some plants had 100% fidelity level, yet these plants were little used by the interviewees, which accounts for the great index of level.
However, 55% (148) of the interviewees also use drugs and medicinal plants, presenting potential risks of interaction between MP and drugs. Therefore, we evaluated the potential interactions as shown in Table 3 and identified 42 potential interactions between MP and drugs. Of these, 90.5% (n = 38) were identified as pharmacodynamic interactions and modifications of the effector organ responses may occur, giving rise to synergistic, antagonistic, and potentiating events. Besides, 9.5% (n=4) were considered as pharmacokinetic interactions, since they are caused by a triggering drug on the absorption, distribution, biotransformation and excretion procedures of another drug, whose effect is modified (Table 3) Potential plant-drug interaction. The lemon balm was the plant that presented the most common interactions among the interviewees since it was the most used by them. Their interaction with sedative and anxiolytic drugs such as fluoxetine, amitriptyline, clonazepam (medicines that the respondents reported use), cause increased sedative activity, and this may occur because the lemon balm exerts an additive effect when simultaneously with central nervous system depressant drugs due to their neurocognitive properties [19]. The clinical significance of drug interactions is related to their type (mechanism) and magnitude (severity). In fact, this information is useful to support the need and intensity of patient monitoring or changes in therapy to avoid possible adverse consequences [20][21][22][23][24][25], since of the 66 Besides, since a great part of the interviewees is of low class, many are not able to acquire these medicines [32][33][34][35][36][37][38].

Conclusion
In summary, when tracing the epidemiological profile and the medicinal plants used, it was possible to conclude that the use of MPs is part of the popular culture of a city of Sergipe, a state of northeastern Brazil, and is frequently used to aid in the relief and/ or cure of symptoms or diseases, as it is also observed in other regions of the country [39][40][41][42][43]. It was also observed that despite advances in the production of medicines, people still use medicinal plants for therapeutic purposes, where the sociocultural aspect has a strong influence [44][45][46][47]. However, medicinal plants are not exempt from causing any harm to human health, since, in addition to toxicity, they may interact with some medicinal products [48][49][50][51][52], if used concomitantly with the plant, reducing or potentiating its effects, as presented in this study. In view of this, there is a need for a rational and safe use of alternative medicines and therapies, as well as the orientation of qualified health professionals and the awareness of the risks and benefits of the concomitant use of the therapies under study in order to prevent health problems [53][54][55][56][57].