**3. 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. [34–38]. 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**).

#### **3.1 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


#### **Table 2.**

*Common plants used by indigenous groups for the treatment of gastrointestinal disorders in Oaxaca, Mexico.* 

 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].

#### **3.2 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* (5), *Quercus* (4), *Piper* (4), *Psidium* (3), *Ocimum* (3), and *Tagetes* (3). The medicinal species introduced to Mexico were excluded from this list, despite being widely used by Oaxacan indigenous groups.

Among indigenous communities, plants are grouped according to gastrointestinal physiological alterations, among which the most common refer to diarrhea (112 plants), stomach pain (90 plants), and dysentery (79 plants). Acute diarrhea is a symptom of gastrointestinal tract infection, which is commonly caused by pathogenic bacteria (e.g., *Escherichia coli*, *Salmonella* spp., *Vibrio cholerae*, *Clostridium perfringens*, *Bacillus cereus*, *Staphylococcus aureus*, *Vibrio parahaemolyticus*, *Campylobacter jejuni, Campylobacter coli, Shigella* spp*., and Aeromonas* spp*.)*, viruses (rotavirus, adenovirus, enterovirus, and norovirus), or parasites (*Giardia lamblia*  and *Entamoeba histolytica)* and is frequently accompanied by abdominal pain, stomach pain, fever, and vomiting [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].
