Current uses and knowledge of medicinal plants in the Autonomous Community of Madrid (Spain): a descriptive cross-sectional study

Background The usage of medicinal plants as a key component of complementary and alternative medicine, has acquired renewed interest in developed countries. The current situation of medicinal plants in Spain is very limited. This paper provides new insights and greater knowledge about current trends and consumption patterns of medicinal plants in the Autonomous Community of Madrid (Spain) for health benefits. Methods A descriptive cross-sectional study was designed for a population-based survey on medicinal plants. The data were collected (May 2018 to May 2019) using semi-structured face-to-face interviews in independent pharmacies, hospital centers and primary care health centers in the Autonomous Community of Madrid. The survey had 18 multiple choice and open-ended questions. Quantitative indices were calculated: Fidelity Level (FL), Use Value (UV) and Informants Consensus Factor (ICF). Chi-square test was used for data analysis. Results Five hundred forty-three people were interviewed. The majority of the participants (89.6%) have used medicinal plants to treat health disorders in the past 12 months, mainly for digestive problems, sleep disorders and central nervous system diseases. A total of 78 plants were recorded, being Matricaria recutita, Valeriana officinalis, Tilia spp. and Aloe vera the most used. The highest UV was found for Mentha pulegium (UV 0.130) followed by Aloe vera (UV 0.097) and Vaccinium macrocarpon. (UV 0.080). The highest FL values were for Eucalyptus spp. (FL 90.47%) for respiratory conditions and, Matricaria recutita (85.55%) and Mentha pulegium (84.09%) for digestive problems. The highest ICF corresponded to metabolism and depression (ICF = 1), pain (ICF = 0.97), insomnia (ICF = 0.96) and anxiety (ICF = 0.95). Participants mostly acquired herbal medicines from pharmacies, herbal shops and supermarkets. Some side effects (tachycardia, dizziness and gastrointestinal symptoms) and potential interactions medicinal plants-drugs (V. officinalis and benzodiazepines) were reported. Conclusion Many inhabitants of the Autonomous Community of Madrid currently use herbal products to treat minor health problems. The most common consumer pattern are young women between 18 and 44 years of age with higher education. In order to confirm the pattern, further research should be focused to investigate current uses of medicinal plants in other Spanish regions.


Background
Complementary and alternative medicines (CAMs) represent different resources that complement or replace conventional therapies [1]. The World Health Organization's (WHO) strategy, 2014-2023, aims to strengthen the role of traditional medicine, emphasizing the importance of promoting and including the utilization of medicinal plants in the health systems of its member countries [2].
The use of medicinal plants has acquired a renewed interest in developed countries and constitutes the first therapeutic strategy for 80% of developing countries. The majority of the global population (87.5%) uses traditional herbal medicine to treat health difficulties [3,4]. Moreover, the growing interest in the employ of medicinal plants is evidenced by the increase of systematic reviews and prevalence surveys about herbal medicines in the last 15 years [5]. In Europe and throughout the Mediterranean area, both wild-collected and purchased from herbalists, supermarkets and pharmacies, is reemerging. This renewed interest in traditional herbal medicine in more developed societies must be seen in the context of changes in the lifestyle, in which it enhances the concept of real and natural products. This leads consumers to perceive herbal medicine as a softer option for health issues [5][6][7].
Previous studies on medicinal plants in Spain are alternatively based on their traditional use [6,7]. All these preceding works aim to study the relationships between plants and human beings in the present and in the past, based on the understanding of herbal remedies which were traditionally used to treat disorders in different health situations [8]. However, the available information on current perspectives and uses of medicinal plants in Spain is very limited compared to other European countries and USA [9,10] and additionally very restrictive to specific areas [11,12].
On the other hand, there exists a widespread belief among population that herbal products, being from natural origin, are not harmful to health [13]. However, medicinal plants can interact with other drugs and thus cause adverse reactions [13,14]. The complete monographs of the German Commission E: Therapeutic Guide to Herbal Medicines includes more than 100 plants historically employed for their therapeutic properties but they are no longer recommended, since scientific evidence has shown potential toxicity or inefficiency [15].
Therefore, based on the state of the art, the aim of this study is to comprehend and deepen the current uses (consumption patterns, perceptions and attitudes) of medicinal plants in different regions of the Autonomous Community of Madrid (Spain), identifying the risks and precautions associated with its use and/or concomitant with conventional drugs.

Study area
The Autonomous Community of Madrid is the most densely populated territory in Spain (676 inhabitants per km 2 ), it hosts the capital of Spain (Madrid). Most of the population is concentrated in Madrid Capital City and in its surrounding metropolitan areas. Even rural areas have Madrid as their referent in the urban lifestyle. The Autonomous Community of Madrid has a very diverse population in terms of its origin (being most of it from other Autonomous Communities), its cultural and socioeconomic terms [16]. This study has tried to represent different random localities with different social environments. In order to determine if the sample surveyed was representative of the population, the latest statistical data available on the website of Institute of Social Sciences (http://www.madrid.org/iestadis/) related to sex, age and occupation were analyzed.

Study setting
A descriptive cross-sectional study was designed for a population-based survey on medicinal plants. This research (PR016/04) was approved on November 2016 by the Ethics and Animal Experimentation Committee, Faculty of Pharmacy, University Complutense of Madrid (Spain).

Questionnaire
The questionnaire (Additional file 1), developed in Spanish language and designed for this study, was based on previous works on medicinal plants [9,17,18] and reviewed by experts in traditional plant-based medicines and pharmacognosy and agreed with experts in public health in order to evaluate the structure, relevancy and clarity of the questions. Before gathering research data, a pilot study was conducted on a sample of 50 people to validate the degree of acceptance and understanding of the questionnaire. Minor modifications, based on the pilot survey, were made in the questionnaire. The final version of the questionnaire consisted on five differentiated parts with a total of 18 multiple choice and openended questions to achieve a better understanding of the knowledge and use of medicinal plants for healthseeking behavior. The first part with five questions collected information on demographic data, including age, gender, educational level, area of residence and occupation. The second part, with four issues, focused on the utilization of herbs for medicinal or health purposes (disease categories, frequency, therapeutic uses, types of medicinal plantsexcluding multi-herbal drug combinations -and forms of administration). This part of the questionnaire included a definition of medicinal plants: "Plants that contain properties or compounds that can be used for therapeutic purposes or those that synthetize metabolites to produce useful drugs" [19] and, being respondents allowed freely to comment which medicinal plants they use to prevent or treat pathologies (open list of medicinal plants). Moreover, regarding the frequency of consumption, it has been considered frequent when the interviewee consumes medicinal plants at least once a month. The third part had three questions about where the consumer acquired the medicinal plants and information on their therapeutic uses. The fourth and the fifth sections containing both 3 questions, were related to the knowledge of potential side effects and identification of concomitant consumption of medicinal plants with conventional medicines, respectively.

Data collection and sample size
Data were collected on a Tablet computer by a research group from May 2018 to May 2019 using a face-to-face interview technique. Participants were recruited directly in a total of 30 independent pharmacies, hospitals and primary care health centers of different districts of the Capital City of Madrid and municipalities of the Autonomous Community of Madrid. The average number of interviewees from each place was from 15 to 20.
Sample population interviewed was voluntary, randomly selected and previously informed (Fig. 1). Over the period of data collection, we conducted a total of 543 surveys. This sample size, based on population size, provides a margin error of 4% at 95% confidence level [20][21][22].

Quantitative indices
The quantitative indices Fidelity Level (FL), Use Value (UV) and Informants Consensus Factor (ICF) were calculated.

Fidelity Level (FL)
FL corresponds to the percentage of informants that use a certain medicinal plant to treat a specific condition and it is calculated as FL (%) = (Np/N) × 100 (Np: number of informants citing a certain medicinal plant to treat a specific condition and N: number of informants citing a medicinal plant to treat any given disease) [23]. This index is used to identify the most frequently used plants to treat a disease or condition.

Use Value of species (UV)
UV measures the relative importance of a medicinal plant to the informants and it is calculated as UV = Ui/N (Ui: number of citations for each medicinal plant and N: total number of informants). It is a quantitative parameter that indicates the relative importance of the different plant species in a community. It is useful to determine plants with the greatest use (most frequently used) in the treatment of a condition. It also allows knowing the confidence in the use and pharmacological characteristics of related plants [17,24].

Informants Consensus Factor (ICF)
ICF estimates the user variability of medicinal plants and it is calculated as (N ur − N t )/(N ur − 1) (N ur : number of used citations in each ailment category, and Nt: number of medicinal plants reported in each ailment category). This index is used to indicate to what extent the information is homogenous. The ranges obtained for this factor vary between 0 and 1. A value close to 1 indicates a relatively high use of the medicinal plant, while a low value close to 0 shows that this plant species is not used by informants for the treatment of an ICF condition. This factor was originally developed by Trotter and Logan (1986) [25] and then readapted by Heinrich et al. 1998Heinrich et al. , 2000.

Data analysis
All data were entered and stored in an Excel Spreadsheet. Frequencies and percentages were calculated using Microsoft Excel. Statistical analysis was performed using chi-square tests in Sigmaplot version 14.0, to analyze data with correlations between the frequency of medicinal plants and certain demographic characteristics. The level of statistical significance was p < 0.05.

Uses and consumption patterns of medicinal plants
The majority of the population interviewed (n = 491, 89.6%) used specifically medicinal plants to treat a disease or a health disorder, from which 20.1% (n = 110) were habitual (more than 4 times/month) consumers and 69.5% (n = 381) were occasional users (1-4 times/ month). Only 10.4% of respondents (n = 57) had never consumed medicinal plants in the last 12 months (Table 2).
A total of 78 medicinal plants used for health problems, were identified in this study ( Table 3) (Fig. 2). Some of these plants were also consumed in combined preparations, such as Valeriana officinalis, Passiflora incarnata and Eschscholzia californica Cham; however, these mixtures have not been taken into account in the study.

Quantitative indices The Fidelity Level (FL)
The results of the Fidelity Level for the 10 most cited medicinal plants showed that the highest values were for Eucalyptus spp. (FL 90.47%) for respiratory conditions followed by Matricaria recutita (85.55%) and Mentha pulegium (84.09%) for digestive problems treatment and, Valeriana officinalis (76.38%) for insomnia ( Table 5).

Place of acquisition preferences and therapeutic resources
Regarding to the place where herbal products were acquired, almost half of the participants preferred pharmacies (n = 253, 51.9%) followed by herbal shops (n = 209, 42.9%) and supermarkets (n = 170, 34.9%), being. The internet resulted in the last position (2.7%) ( Table 8).
Most interviewers initiated the consumption of medicinal plants for prevention and treatment following the recommendations of friends and family (n = 226, 46.4%), being less who started by their own initiative (n = 216, 44.3%) ( Table 8). The information concerning the therapeutically uses of medicinal plants came mainly from family and friends (n = 234, 48.1%), followed by pharmacist (n = 210, 43.1%) and the internet (n = 160, 32.8%) ( Table 8).

Subjective perception of risks and precautions of medicinal plants
Half of the respondents (n = 227, 46.6%) believed that medicinal plants could cause adverse reactions such as conventional drugs do while the other half of the sample population did not (n = 260, 53.4%). Moreover, it was investigated if any of the respondents had suffered any side effect when consuming herbal products for therapeutic purposes. Of those respondents, 17 (3.5%) reported that they had suffered some adverse reaction such as anxiety, tachycardia, dizziness and gastrointestinal symptoms ( Table 9). The potential risk in respect of interactions between medicinal plants and conventional drugs was also investigated. Several respondents have consumed medicinal plants along with conventional medicines (n = 103; 21.1%) (

Discussion
This work reveals new insights and greater knowledge about the main reasons and current consumption mode of medicinal plants in the population of the Autonomous Community of Madrid for health benefits.
The Community of Madrid has a very varied population and it is very densely populated. Therefore, data from our study were compared with those available from the Institute of Social Sciences to find out whether the surveyed population is representative of the population of this Spanish region. As evidenced demographic parameters are representative (i.e. active population percentage which is 43.6% and range of age which are 55.3% for 18-44, 27.3% for 45-64 and 17.3% for ≥65 years) [16].
Regarding medicinal plants, it was unconcluded that it was higher than the one estimated for other Spanish cities [12]. The main reasons for this finding are the consumer's perception of efficacy and safety as well as the easy access. In this study, the most common consumption pattern of medicinal plants is young women, between 18 and 44 years of age, with higher education. There is statistically significant differences in  consumption frequency related to gender respondents, being higher in women (P < 0,001). This high prevalence in the preference of medicinal plants by the female gender has been also confirmed in previous studies [28]. As surveys have been conducted in different health centers, the fact that participants were predominantly women may be due that visits to pharmacies, nurses and doctors in Spain are more frequent in women [29] alongside satisfaction with complementary and alternative medicines [30]. Moreover, a statistically significant finding related to age ranges was found [respondents aged 18-44 consumed medicinal plants more often than those in 45-64 age range (P = 0,010) and even more often than those ≥65 years (P < 0,001)]. This pattern, contrasts with studies performed in other parts of Europe where the frequency of consumption is higher in older people rather than in younger people [31]. Moreover, studies from the USA found that medicinal plants consumption is more frequent in middle-aged people [10]. These differences may lie in the area where study was conducted, economic level and consumer trends. Particularly, the Autonomous Community of Madrid has the highest Gross Domestic Product per capita in Spain. In addition, it is one of the Spanish regions most influenced by urbanization and where there is not such a strong connection to traditional use of medicinal plants as in other areas of Spain. Furthermore, there is a growing trend, especially amongst younger people with higher educational level, to use natural products to succeed a healthy lifestyle and mentality [3,31].  One of the limitations found in former published studies on prevalence of medicinal plants consumption, unlikely to the one presented, is on the one hand that "medicinal plants" concept is not properly defined, and on the other hand, a list of medicinal plants is providing limiting the knowledge of their use [5]. Of the 78 identified plants, women reported using 72 while men reported 49. Moreover, most people surveyed use them appropriately in relation to diseases for which they are found to be effective. There were no significant differences (p = 0.242) in medicinal plants consumption between female and male. However, preferences for some medicinal plants were found among gender. Melissa officinalis L, Cynara scolymus L., Echinacea angustifolia DC, Equisetum arvense L. and Mentha piperita L. were preferred by women whereas Vitis vinifera L. and Tribulus terrestris L. were preferred by men. Moreover, in this study, Vaccinium macrocarpon Ait. Consumption was exclusive to women in order to prevent uncomplicated acute lower urinary tract infections recurrence.
Women's urethra is shorter than that of men's allowing bacteria rapid access to the urinary bladder [32].
It is necessary to emphasize that some of the medicinal plants consumed by the population of the Autonomous Community of Madrid are considered as threatened/vulnerable/endangered by the IUCN Red List. These plant species include in this Red list are Aesculus hippocastanum (vulnerable), Arnica montana (least concern), Coffea arabica (endangered), Ginkgo biloba (endangered), Laurus nobilis (least concern), Rhamnus purshiana (least concern) and Tilia cordata (least concern). Particularly, those plant species classified as least concern are not considered to be at threat from extinction and, the future conservation actions are aimed at controlling agriculture practices and include an international legislation. However, Aesculus hippocastanum is classified as vulnerable because this plant species suffer from severe defoliation by the invasive insect pest Cameraria ohridella. The conservation actions consists on Cameraria ohridella control and research, ex situ  . high temperatures). There are several conservation actions for Coffea arabica such as exsitu conservation and, education and awareness programs. Finally, Ginkgo biloba is threatened because its logging and wood harvesting. The conservation action for this specie has been widespread in cultivation. It is therefore important that investigations with these species follow the guidelines "IUCN Policy Statement on Research Involving Species at Risk of Extinction" that guarantee the increase and survival of these plant species, bearing in mind that the conservation of these research sources is of clear scientific interest, and in the case of our study, of great therapeutic interest [33][34][35][36][37][38][39].
Regarding forms of consumption, the effectiveness of medicinal plants depends on the correct use and preparation. Decoction and infusion are the main preparation methods for herbal teas of roots, barks and seeds. Herbal teas are closely linked to self-medication, being this form of administration not suitable for active principles with narrow therapeutic margin. Tablets/capsules are commonly used for medicinal plants oral administration because of good bioavailability, therapeutic adherence and patient comfort [40].
Concerning accessibility to medicinal plants, most of the herbs are freely available in different places for its acquisition, even at supermarkets (i.e. Matricaria recutita, Camellia sinensis and Mentha pulegium) whereas there are other medicinal plants that are only available in local pharmacies and herbal shops (i.e. Verbascum thapsus and Ajuga chamaepitys). Participants' perception is that medicinal plants dispensed in pharmacies have better quality and efficiency than those from other acquisition places; however, medicinal plants bought in pharmacies are more expensive than in other sales establishments. This explains why the purchase of medicinal plants in supermarkets and herbal shops is very high. This pattern of herbal products acquisition for therapeutic purposes has also been observed in other countries [41]. However, within Spain, patients from a social security primary health care center in Barcelona bought medicinal plants first in herbal shops, then in supermarket and in pharmacies in third place [12]. The role of the pharmacist is consolidated as the health professional and expert in medicinal plants and pharmacy offices as a reference in the dispensation of medicinal plants, offering quality guarantees.
Due to the wide traditional utilization of medicinal plants and the limited existing clinical trials, there is a lack of scientific evidence on the efficacy and safety of medicinal plants [4]. Adverse drug reactions is defined as "all noxious and unintended responses to a medicinal product" [42,43]. There is a common perception of safety of medicinal plants as "natural" and "harmless", which could lead to an under-reporting of adverse reactions. Adverse reactions may be due both to medicinal plants and to other factors (i.e. adulteration, lack of botanical identification) [44]. Studies conducted on natural products' perception for health, show an increase in the demand for information about medicinal plants [45,46]. It is necessary to include medicinal plants consumption in the usual medical history to identify possible adverse reactions and drug interactions [47]. Many health professionals have not received academic preparation on medicinal plants during their Degree studies [48]. In Spain, only pharmacists receive university education on medicinal plants. This lack of knowledge is a limiting factor when health professionals recommend medicinal plants and identify possible adverse reactions and interactions. The need to include medicinal plants in undergraduate training to the rest of health professionals is presumed.
Currently, there are a paucity of robust data on interactions between medicinal plants and conventional medicines [49]. However, it has been found that certain plants can lead to therapeutic inefficiency or drug toxicity. There is evidence of interactions for Hyperycum perforatum L. with digoxin, indinavir and cyclosporines [50]. Moreover, Ginkgo biloba L. Mant. Pl. can increase insulin elimination or interfere with omeprazole [51]. Furthermore, and in relation to the medicinal plants, that are more consumed concomitantly in this study, there are evidences of pharmacodynamics interactions between M. recutita and lormetazepam, M. officinalis and alprazolam, and V. officinalis and lormetazepam, increasing hypnotic effect of these benzodiazepines [51]. The clinical effects of the interactions depend on patient (age, genetic and pathologies), medicinal plants (species, dose and duration) and concomitant medication (dose, activity and posology) making it difficult to detect interactions if health personnel do not know its use.
Finally, several participants told that neither they reported medicinal plants consumption to these health professionals nor did they ask. This leads to a potential underreporting of adverse reactions and interactions with medicinal plants and, supports the need in the academic training of health sciences personnel to include subjects of medicinal plants in undergraduate degree.

Conclusions
In this paper, we have explored medicinal plant uses, consumption patterns and attitude towards medicinal plants of the population of the Autonomous Community of Madrid that attend health-related centers. This study