Medicinal Plants Used by Indigenous Communities of Oaxaca, Mexico, to Treat Gastrointestinal Disorders

The use of medicinal plants for the treatment of gastrointestinal disorders and ethnodiseases such as diarrhea, stomachache, dysentery, “empacho” (blockage), and bile is a common strategy among indigenous communities. It is estimated that approximately 34% of medicinal plants are used to treat diseases of the digestive tract. In Mexico, gastrointestinal infections caused by bacteria, parasites, or viruses represent one of the main causes of death in children in rural populations. Our objective was to document the use of medicinal plants used by the indigenous groups of Oaxaca, Mexico, for the treatment of gastrointestinal disorders, based on previous studies, experiences, and field observations in indigenous communities and supplemented with bibliographic references. In Oaxaca, there are 16 indigenous groups, the largest being the speakers of the Zapoteco, Mixteco, Mazateco, Mixe, Chinanteco, Amuzgo, Tacuate, Chatino, and Cuicateco languages. In this review of the medicinal plants used for gastrointestinal disorders, 186 species were grouped into 147 genera and 71 botanical families, among which the largest number of species belonged to Asteraceae (29), Fabaceae (15), Euphorbiaceae (9), Solanaceae (9), and Lamiaceae (9). Different pharmacological studies showed potential for preventing microbial and fungal pathogens that cause gastrointestinal disease.


Introduction
Medicinal plants are key elements of traditional medicine because they are part of the collection of knowledge and cultural heritage of sociocultural communities. Communities are often repositories and users of medicinal plants, and both rural and urban social groups with rural or indigenous origins have knowledge of these plants. Based on ethnobotanical, ethnomedicinal, and ethnopharmacological studies, the plants that are used by different healers and families of the Tarahumara, Yaqui, Chontal, Nahuatl, Mazahua, Otomi, Mixteco, Zapoteco, Mixe, Maya and Tzotzil groups, and all Mexican indigenous groups are symbolic [1].
In Mexico, gastrointestinal diseases are common in communities that are highly marginalized and poverty-stricken and are often transmitted through the fecal-oral route and the consumption of contaminated water and food. The infant population is the most vulnerable, both in terms of incidence and vulnerability [2]. In 2012, approximately 20% of the population of Chiapas, Guerrero, and Oaxaca did not have access to an adequate quality of water. This problem was exacerbated because only between 65 and 75% of houses have adequate waste management systems. Gastrointestinal diseases in children under 5 years of age directly affect mortality rates (19.2-19.4%) and mainly occur in marginalized communities [3]. These observations suggest that minimizing gastrointestinal diseases is dependent on the social environment of the community, access to clean water and food safety. As such, the symptoms and syndromes of diarrhea, stomachache, gastric atrophy, and enteric fever are associated with bacterial, fungal, parasitic, and rotavirus agents [2], and the frequency of these symptoms among children varies from community to community.
Medicinal plants are commonly used by communities for the treatment of gastrointestinal disorders through plant infusions, maceration, chewing, poultices, and different types of extracts (alcoholic or aqueous) [1]. Some studies have documented the traditional uses of medicinal plants by healers, their conservation, and their cultural importance in different indigenous groups [4][5][6][7][8][9]. Other studies have contributed ethnobotanical knowledge of medicinal plants [10][11][12]. The evaluation of phytochemical compounds with medicinal activity is also a subject of interest [13][14][15][16]. One aspect in which different authors have devoted a great amount of attention to is the antiparasitic and antimicrobial effects of medicinal plants for the treatment of diarrhea and other gastrointestinal disorders [17][18][19][20][21][22][23][24][25].
Research in natural products is often based on ethnobotanical information. One goal of ethnopharmacology is to improve the understanding of the pharmacological effects of plants on health, especially for indigenous communities that are highly marginalized and poverty-stricken. In this study, we examined plants used for the treatment of gastrointestinal disorders such as diarrhea, dysentery, and abdominal pain. The objective of this work was to document the use of medicinal plants used by the indigenous groups of Oaxaca, Mexico for the treatment of gastrointestinal disorders, based on previous unreported studies, experiences, and field observations in indigenous communities. Our results are supplemented with bibliographic reviews.

Sociocultural and ethnographic context of Oaxaca, Mexico
Mexico has an indigenous population of 12.25 million (10.1% of the total), of which 7.38 million speak an indigenous language [26]. It is estimated that there are 1.2 million speakers in Oaxaca over 3 years of age that speak an indigenous language. Oaxaca is the state with the largest indigenous population (32.2% of its total population) and has 245 municipalities where more than 40% of the population speaks indigenous languages [26][27][28]. However, in Mexico, 24.4 million people consider themselves indigenous [26,29], a figure that is higher than the total number of inhabitants of several European countries and is of great importance in the preservation of culture, biodiversity, and biocultural heritage. Indigenous peoples are also associated with the use of medicinal plants.
Based on the vegetation, ecosystem, biome, and indigenous settlement maps, Toledo et al. [30] identified 26 indigenous regions in Mexico. These regions coincide with the zones of greatest biodiversity and pluriculturality or indigenous settlements and are also where protected natural areas are located. In Oaxaca, eight

Relationship between indigenous groups and endemic medicinal plants used for gastrointestinal disorders
Among rural and indigenous communities, the concept of health and disease is holistic. As such, the human body develops its organic and metabolic functions without physical deterioration and includes mental, mystical-spiritual, and psychological aspects (symbolic reality). Social, cultural, and ethnic concepts are implicit in the perceptions of health and disease, and based on these concepts, the healingtherapeutic benefits of medicinal plants are sought. From the indigenous perspective, the causal explanations of illness are complex. The body suffers symptomatic imbalances resulting from physical, emotional, or mental deterioration, which are consequences of "susto" (fright), anger, interpersonal conflicts, cold currents, harmful foods (cold, hot, types of meat, cravings, etc.), sexual relations, witchcraft, etc. [34][35][36][37][38]. Consequently, the factors that produce imbalances in the body, in this case stomach problems, are to be avoided.
The knowledge and use of medicinal plants in indigenous communities is changing due to the introduction of pharmaceutical products recommended by health professionals. Giovannini et al. [39] note two trends in support of this fact: the complete displacement of medicinal plants by pharmaceutical products and the coexistence between clinical medicine and the use of medicinal plants. Thus far, local indigenous knowledge for the treatment of cardiovascular diseases, cancers, diabetes, and other prevalent diseases has been disseminated, which is why patent medicine is used. However, there are some examples of healing via the use of medicinal plants. In cases of chronic diarrhea caused by pathogens, the use of plants has been beneficial, such as plants used to treat diarrhea caused by Salmonella spp. [24]. In Oaxaca, acute diarrhea and acute respiratory infections are the main causes of mortality in children under 5 years of age [40].
The prevalence among Oaxacan children of microbial or parasitic gastrointestinal diseases, which cause acute diarrhea and other problems, has forced communities to resort to medicinal plants. Consequently, under these circumstances, there is a set of common species among indigenous communities that are used similarly, provided that their ecological conditions are also similar. It should also be noted that knowledge may be treated differently between different ethnic communities, especially when faced with common health problems. For example, the Mixe, Mixteco, and Zapoteco groups of the Sierras, located in temperate regions, commonly use Chenopodium graveolens, Lantana achyranthifolia, Baccharis salicifolia, and Miconia mexicana, although the local names used by each region are different. Additionally, the Chinanteco groups and Zapoteco of the Istmo use similar plant species ( Table 2).

Healers and medicinal plants
Within Oaxacan indigenous groups, the healers play essential roles as therapists or ethnopractitioners and are not referred to as shamans, witch doctors, or herbalists. Here, we only refer to the cures or treatments using plants recommended by healers for the treatment of gastrointestinal disorders. The indigenous healers have social recognition in the communities as persons of knowledge, skills, and healing practices. These healers have the facilities to explain the physical and nonphysical causes of diseases through a symbolic, verbal and corporal language, and resort to deities to exercise healing techniques. The body of knowledge is a legacy inherited or acquired from their ethnic medical culture and becomes a depository with the capacity to incorporate medical experiences regarding the descriptions of diseases, anatomy, and physiology of the human body [1,34,38,46,47].
The healer's diagnosis is based on the spirit, soul, and body, which are closely interconnected, to define health and disease. In Oaxacan communities, Mixe and Mazateco healers use psychotropic or hallucinogenic plants and mushrooms for successful diagnoses and healing. These hallucinogens are used as a mechanism to access supernatural forces and as interlocutors to ward off malignant agents [34,46,47]. The remedies or treatments recommended by healers for gastrointestinal problems vary from diets, teas, maceration or poultices of medicinal plants, changes in eating habits such as avoiding foods considered "hot" or "cold," avoiding animals or people, sun exposure, or environmental changes in temperature, such as avoiding cold water, etc.
María Sabina was a well-known healer among the Mazateco Indians of the Sierra de Huautla de Jiménez in Oaxaca and throughout Mexico. After her death, she was recognized as a symbolic character of the Mexican healers. She used mushrooms (e.g., Psilocybe zapotecorum and Psilocybe mexicana) and hallucinogenic plants (e.g., Salvia divinorum) to obtain divine powers both to diagnose and to restore the health of the patient. In the case of gastrointestinal diseases, all recommendations are preventive/curative and are accompanied by psychospiritual rituals of protection, reintegration, and cleanliness of the soul. She is known to have said, "The health services provided by healers and Western medicine should not be lucrative," [48,49]. Gouania lupuloides (L.) Urb.

Plants used in indigenous communities for the treatment of gastrointestinal disorders
Medicinal plants are essential natural resources in the indigenous communities of Oaxaca, Mexico; they are easily accessible and there is a high diversity of species and forms of use for the treatment of diseases of the digestive tract. The region has the greatest level of diversity and endemism of species of phytotherapeutic use [50]. Based on a bibliographical compilation and field notes of visits to the indigenous communities of Oaxaca, a short list of medicinal plants used for gastrointestinal disorders was obtained ( Table 1A). The compilation consists of 71 botanical families, among which the greatest number of species is in the families Asteraceae (29), Fabaceae (15), Euphorbiaceae (9), Solanaceae (9), Lamiaceae (9), Verbenaceae (6), Myrtaceae (5), Malvaceae (5), and Fagaceae (5). These families included 147 genera and 186 endemic species [50]. The genera used most frequently were Croton  [51]. For the treatment of vomiting, constipation and parasites, between 28 and 31 plant species are used. For the condition known locally as "empacho" (gastrointestinal disease) as well as for indigestion, ulcers and gastritis, between 17 and 39 species are utilized (Table 1A). It is important to note that we refer to the local descriptions of symptoms and the disease names that are used by Oaxacan indigenous communities.
The indigenous knowledge of medicinal plants includes the different phases of use, correct identification of the species (although they do not have systematic botanical studies), wild or cultivated origin, collection time (morning, noon, afternoon, or night), plant part to be used, and processing required for use. Each of these elements affects the effectiveness of the plant [8,17,51]. The leaves, stems and flowers are the most used parts, and the bark, roots and seeds are used less often ( Table 1A). The form of use or extraction preparation ranges from infusion and cooking in water, maceration in ethyl alcohol (Dorstenia drakena L. and Barkleyanthus salicifolius (Kunth) H. Rob. & Brettell) or cane alcohol (Saccharum officinarum L.) and consumed as tea (oral), or as a topical application between the stomach and intestines. Additionally, the fresh crushed leaves or leaves macerated in ethyl alcohol can be ingested or applied topically (rubbed onto the affected part). Plants for treating dysentery are used as purgatives or for treating constipation as rectal washes and include Eryngium foetidum L., Capraria biflora L., Prosopis laevigata, and Solanum rostratum Dunal (Table 1A).
Bark is often cooked or used as an infusion in hot or cold water; it is a common treatment for diarrhea, dysentery and related symptoms. The bark of Semialarium mexicanum (Miers) Mennega, Hymenaea courbaril L., Quercus oleoides, Hintonia latiflora, and Guaiacum coulteri is used to treat ulcers or gastritis, and the bark of Amphipterygium adstringens is used to treat stomach cancer. The roots of some plants have shown to be beneficial to treat diarrhea, stomach pain, and intestinal infection. In addition, the use of fruits and seeds to treat diarrhea, dysentery, constipation, and "empacho" is mentioned. For example, the fruits and seeds of the chili pepper (Capsicum annuum L.) are used for the treatment of dyspepsia (inflammation of the digestive tract), diarrhea, and dysentery. An infusion of guava leaves and roots (Psidium spp.) is used to treat diarrhea, dysentery, stomach pain, flatulence, and vomiting. The peel of the fruits of Curatella americana L. and Persea americana Mill. and the stigmas of the corn flower (Zea mays L.) are made into an infusion to treat stomachaches. The seeds of Carica papaya L. are used to treat diarrhea, vomiting, fever, intestinal inflammation, and parasites (Table 1A).
"Empacho" is a digestive ethnodisease recognized by traditional Mexican people. This disorder primarily occurs in children and does not correspond to a specific clinical diagnosis, but is culturally recognized in all Mexican rural communities. Empacho is characterized by discomfort caused by the intake of food that is difficult to unfold, and the healer or mother of the child indicates that food is "stuck" to the stomach or intestine. Symptoms include abdominal pain, lack of appetite, diarrhea, flatulence, and vomiting. The treatment includes the use of ash-or salt-containing oral plant infusions, purgatives, and massages [52]. Some traditional treatments recommend infusions made from the bark and/or leaves of Guazuma ulmifolia Lam. complemented with spoonful of castor oil and massages (sobadas) that "release the empacho" [53].
Another ethnodisease associated with gastrointestinal disorders is "bile or bile leakage." The healer and adults report "pounding" (vibrations) from an area near the stomach, which is accompanied by pain in the esophagus. Symptoms include loss of appetite, headache, feeling of "bitterness" in the mouth upon waking up, and fatigue. Pseudognaphalium attenuatum DC., Agastache mexicana spp. Xolocotziana, Hintonia latiflora, Loeselia mexicana, Tecoma stans, Zornia thymifolia, Anoda cristata, Oenothera rosea, Verbena litoralis, and Calea ternifolia var. Ternifolia are used to treat bile (Table 1A). For gastrointestinal intestinal disorders in children, Psidium guajava, Byrsonima crassifolia, and Quercus spp. are used [53]. Mixe communities use fruit and bark infusions of G. ulmifolia to treat diarrhea and hemorrhages [14], whereas Cestrum nocturnum is used among the Zapotecas from the southern highlands and the Chinantecos of Oaxaca [53,54].
Several studies have shown the importance of flavonoids, tannins, terpenoids, and alkaloids present in medicinal plants used for the treatment of gastrointestinal diseases. Other mechanisms of action include antispasmodic activity, delaying of intestinal transit, suppression of intestinal motility, stimulation of the adsorption of water, and a reduction in the secretion of electrolytes [20]. The compounds most frequently reported are terpenoids (monoterpenes, sesquiterpenes, di-, and triterpenes), flavonoids (flavones, flavonols), tannins (condensed and hydrolysable), and volatile compounds, which are derived from the essential oils in aromatic plants.
Root extracts of Tagetes erecta have shown to have high efficacy against Grampositive bacteria (Staphylococcus aureus, Bacillus subtilis, and Micrococcus luteus), Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa), and fungi (Candida albicans and Aspergillus niger). Flowers of T. erecta have been shown to contain thiophene derivatives, terpenoids, alkaloids, flavonoids, and carotenoids [55]. Similarly, methanol extracts of Tagetes lucida yielded coumarins with high antimicrobial activity against Gram-positive and Gram-negative bacterial strains, with greater inhibition of V. cholerae as well as antifungal activity. The antifungal activity of T. lucida results from the presence of dimethoxy: 6,7-dimethoxy-4-methylcoumarin and scoparone (6,7-dimethoxycoumarin) [56] and is effective against Helicobacter pylori [57]. In traditional Oaxacan medicine, the anthelminthic effects of Chenopodium ambrosioides (epazote) along with the epimastigotes of Trypanosoma cruzi have demonstrated efficacy against Entamoeba histolytica infections due to the effect of limonene [58]. 8

Antipathogenic efficacy of medicinal plants
A natural question about the use of medicinal plants for treating gastrointestinal disorders is: how effective are the uses of plants in controlling or preventing infections by pathogenic agents? Several in vitro studies have been conducted that aimed to evaluate the biological activity of plant extracts against enteropathogenic bacteria (Escherichia coli, Shigella sonnei, Shigella flexneri, Salmonella, and Campylobacter) and parasites (Giardia lamblia and Entamoeba histolytica) responsible for diarrhea, dysentery and/or gastric disorders [59][60][61]. Several chemical compounds (alkaloids, tannins, flavonoids, and terpenes) responsible for the pharmacological effects of these plants have been identified and isolated [62,63]. Examples of biological activity of native plants of Oaxaca, Mexico, used for the prevention and control of gastrointestinal disorders are listed in Table 3.
The experiences in the communities of Oaxaca indicate that the roots and aerial parts of Geranium mexicanum Kunth and the flowers of Chiranthodendron pentadactylon are effective to treat diarrhea, dysentery, and stomach pain ( Table 3). The methanolic or aqueous extracts of these plants showed high antibacterial activity against Shigella flexneri and Shigella sonnei at minimum inhibitory concentrations of 8 mg/mL. Both extracts can be considered an alternative strategy to treat enteric pathogens resistant to common drugs [60]. In biological experiments using mice, it was demonstrated that the molecule (−)-epicatechin, which is isolated from Geranium mexicanum, has high antiprotozoal activity (Giardia lamblia) in concentrations of 0.072 μmol/kg, which is the dose required to kill 50% of microorganisms [59].
Calzada et al. [69], found that (−)-epicatechin and tiliroside, isolated from extracts of C. pentadactylon flowers, were effective against E. histolytica, G. lamblia, E. coli, S. sonnei, S. flexneri, Salmonella sp., and Vibrio cholerae. In another work, Calzada et al. [11] determined that root extracts of G. mexicanum had a greater hyperperistaltic effect than the extracts of Lygodium venustum, Chenopodium ambrosoides, and C. pentadactylon, which was similar to the effect of the drug loperamide, which is used to control acute and constant diarrhea associated with intestinal inflammation. In experiments with mice, the methanolic extracts of G. mexicanum, Bocconia frutescens, and C. pentadactylon in a concentration of 300 mg/kg of body weight had high inhibitory or intestinal antisecretory activity against V. cholerae. The activity of these extracts exceeds the effect of the drug loperamide [72]. A similar effect was determined with extracts of C. pentadactylon flowers [73]. B. frutescens also showed inhibitory activity against S. aureus and E. coli [60]. These results show that G. mexicanum, C. pentadactylon, and B. frutescens have medicinal properties and are effective for the treatment of diarrhea, among other gastrointestinal problems ( Table 3).
The methanolic extracts Ocimum basilicum and Artemisia ludoviciana have inhibitory effects against V. cholerae, and the minimum bactericidal concentration varies from 0.5 to 3.0 mg/mL. The extracts have a degradative effect on the cellular membranes of V. cholerae, which increases membrane permeability, decreases cytoplasmic pH, hyperpolarizes the membrane, decreases the cellular ATP concentration, and consequently causes cell death [65]. This result indicates a chemical modification of the growth medium and induction of the death of the pathogen. For example, Hussain et al. [62] reported that basil contains essential oils (linalool, epi-α-cadinol, α-bergamotene, and γ-cadinene) that exert antimicrobial activity against S. aureus and B. subtilis. Similarly, the essential oil of A. ludoviciana contains camphor, 1,8-cineole, and camphene, which were effective against Acanthamoeba castellanii, Leishmania infantum, and Trichomonas vaginalis [66].  Table 3.
The extracts of Cnidoscolus aconitifolius, Crotalaria pumila, and Anoda cristata ( Table 3) inhibit bacterial growth. The flavonoids acacetin and diosmetin from A. cristata have been shown to inhibit up to 90% of H. pylori growth. These data suggest that, through the use of nutraceutical food plants, H. pylori infections can be prevented [70]. Ambrosia artemisiifolia L. is used to treat stomach pain and contains isabelin, a germacranolide sesquiterpene dilactone with antimicrobial activity against S. aureus and Candida albicans [64].

Remarks
Medicinal plants continue to play an indispensable role in the daily life of rural and urban communities. However, their use is controversial, and they are often only used in teas or hot drinks; they are not associated with healing properties. Through interactions with the indigenous communities of Oaxaca, Mexico, it was found that all households use the inherited knowledge of medicinal plants. In the regions furthest from the urban centers where the hospitals are located, medicinal plants are part of the survival strategy.
In the communities of Oaxaca and other regions of Mexico, healers (the generic name for traditional practitioners) are called "yerberos" (herbalists) because they only use plants. The consultation or intervention of the healers occurs when the symptoms of the disease or ethnodisease continue after the patient takes the "remedies" (teas, crushed, chewed, potions, etc.), which are prepared by the adults of the family. We define ethnodisease as a disorder that has no somatic symptoms, description of organic or metabolic dysfunction, or association with clinical symptomatology. Thus, "empacho" is often associated with indigestion, but has a broader sociocultural description than a gastroenterological disorder.
The use of antibiotics for infectious gastrointestinal diseases is unconscionable among the users of pharmacological medicine and has generated collateral damage, including antibiotic resistance of pathogenic microorganisms. Cases of antibiotic resistance are increasingly frequent, and thus, medicinal plants will fill an important niche once their antibacterial, antiprotozoal, antisecretory, spasmolytic, and anti-inflammatory protective effects are demonstrated. In addition to these benefits, antiradical and antioxidant activity effective against gastroenterological disorders have been shown after the frequent consumption of teas. Advances have been made in the knowledge of antipathogenic effects of medicinal plants and their association with specific compounds. However, not all plants used by the indigenous groups of Mexico and Latin America are being studied and documented.