The Ethnopharmacological Literature: An Analysis of the Scientific Landscape in the Cerrado in Central-Western Brazil

Research on pharmacology and phytochemistry originating from medicinal plants has resulted in various publications highlighting the Cerrado in central-western Brazil, which has a remarkable diversity of plant species. The reserve area selected was the Cerrado stricto sensu settlement “17 April”, Mato Grosso do Sul (MS), Brazil. However, no ethnopharmacological review focusing on the plants present in the reserve area exists, even though the consumption of medicinal plants is a widespread practice. The aims of this study were to 1) survey and document the medicinal plants present in the reserve area; 2) provide an overview of recent ethnopharmacological, phytochemical and pharmacological studies of these species; and 3) provide insight for future studies. A literature search was conducted, and relevant information was collected from authentic resources using databases such as Science Direct, PubMed, Google Scholar, Web of Science and Scopus, as well as peer reviewed articles, books and theses. Eighty-nine species belonging to 39 different families were found; the most abundant were Fabaceae (n = 13), Myrtaceae (n = 7), Rubiaceae (n = 7) and Bignoniaceae (n = 5). In terms of it empirical use, the most utilized parts were leaves (41%), bark (22%) and roots (15%). The most widespread traditional use, according to the literature review of the following plants involves the treatment of gastro-intestinal system diseases (41 spp). Chemical studies reported a high presence of terpene, phenol, and alkaloid classes. Only three are listed in the RENISUS: Casearia sylvestris, Copaifera langsdorffii and Stryphnodendron adstringens. This study demonstrated a large number of medicinal plants in an area of the Cerrado in the state of Mato Grosso do Sul, Brazil. Noting the importance of biodiversity for the development of new pharmacological approaches, many studies prove the empirical use of medicinal plants.


Introduction
Brazil is characterized by some of the greatest biodiversity on the planet due to the presence of different biomes, such as the Amazon (tropical forest), Caatinga (thorn forest), Pantanal (flooded pasture), Pampas (subtropical pastures or pastures), Atlantic Forest (deciduous forest) and Cerrado (savanna) (Guerra et al., 2020). The Cerrado is the second largest biome in South America, occupying an area of approximately 22% of the Brazilian territory, and had the second greatest biodiversity richness (Sano et al., 2019). The state of Mato Grosso do Sul is located in midwestern Brazil, and most of its territory is occupied by the Cerrado (Amaral et al., 2017). Nevertheless, 46% of the original Cerrado area has been converted to pasture and cropland and is continually threatened by the indiscriminate use of fire (Durigan & Ratter, 2015;Strassburg et al., 2014).
The study of ethnopharmacology is closely related to sustainable development, as it is an effective way to develop medicines from the perspective of traditional plant use. In this sense, the importance of studies in this area is clear, as they contribute to the improvement of the traditional application of natural products, and they emphasize the importance of biodiversity for the sustainability of local populations (Di Stasi et al., 2002). In this context, the Brazilian government encourages the use of herbal remedies and medicinal plants as a strategy to improve the use of Brazil's biodiversity and public access to herbal medicines.
In this study, we conducted a 1) literature survey and documented the medicinal species present in the reserve area of the settlement "April 17", MS, Brazil, in the Cerrado biome; 2) Exhaustive research has evaluated the jas.ccsenet. current sta properties herbal me subsistenc and the sc any knowl scientific s and well-b

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Sites mework of th d the reserve ar .  ; the Myrtaceae (n = 7), Rubiaceae (n = 7) and Bignoniaceae (n = 5) were the most species-rich families ( Table 1). The leaves (41%), bark (22%) and roots (15%) were the most commonly reported plant parts for popular use (Table 1). Table 1 presents information on previous scientific research, describing the forms of use of the plants,  as well as the useful part of the plant and its use. These plant species are used for the treatment and prevention of many ailments and due to the widespread use of terms transcribed in review the species were grouped under 10 specific and 2 general categories diseases. The most widespread traditional use, according to the literature review of 10 specific categories diseases of the following plants involves the treatment of gastro-intestinal system diseases (DSD, 44 spp), followed by the endocrine system diseases (ENM, 24 spp), infectious diseases (IPD, 20 spp), musculoskeletal and joint diseases (MCT, 20 spp), respiratory system diseases (RSD, 19 spp), skin, eye, ear, nose and oropharynx diseases (SST, 18 spp), obstetrics, gynecology and urinary-tract diseases (GUS, 18 spp), malignant diseases (NEP, 9 spp), cardiovascular system diseases (CSD, 8 spp) and central nervous system diseases (NSD, 6 spp) ( Figure 2). Many species have been reported grouped into 2 general categories, as for the treatment inflammatory diseases (ID, 16 spp) and other diseases (OD, 41 spp) ( Figure 2). The symptoms and effects mentioned for DSD includes antidiarrheal, carminative, abdominal disorders, dysentery, purgative, laxative, hemorrhoids, hernia, gastritis, ulcer, liver and spleen diseases, flatulent dyspepsia liver abnormalities, gallstones, heartburn, kidney pain and intestinal colic. According to the World Health Organization, gastro-intestinal system diseases (diarrhoeal) are the main cause of death in children under five years old, and there are almost 1.7 billion cases of childhood diarrhoea every year, with approximately 525,000 deaths (Kirk et al., 2017). The OD category include as an example snake bites, aphrodisiac, tonic, emetic, astringent, scurvy, anthelmintic, swelling, malaise and stings insects.   et al., , Silva et al., 2011bResende et al., 2015) Tapirira guianensis Aubl.

Pharmacological and Phytochemical Studies
Many of the species found in the study area have already been chemically and biologically evaluated, possibly in an attempt to prove their popular indication.  2). These data show high herbal diversity among medicinal plants in the reserve area of the settlement "April 17", located in Casa Verde district, Nova Andradina city, MS, Brazil, as well as great potential for further studies on therapeutic activities. Moreover, the conservation of biodiversity ensures the sustainability of natural resources and allows the maintenance of various services essential to human well-being.
In the review, only twelve species were not chemically studied, and fourteen did not have associated pharmacological studies. Among the studied species for which contents were isolated, the predominant class of substances was terpenes, followed by phenolic compounds and alkaloids (Table 2).  Table 2. Pharmacological and chemical studies of the species found in the reserve area of the settlement "April 17", located in Casa Verde district, Nova Andradina city.

Brazilian Government-Public Access to Herbal Medicines
In Brazil, the Unified Health System (SUS) is in place and consists of a public health system that covers everything from primary care to organ transplantation, guaranteeing full, universal and free access by the entire country's population. Among the existing projects of the SUS is the RENISUS (National List of Medicinal Plants of Interest to the SUS), which contains medicinal plants that have the potential to generate products of interest to the SUS. Among the listed species are 71 plants popularly used and scientifically confirmed. The purpose of the list is to guide studies and research that can support elaboration of the list of herbal medicines available for safe and effective use by the population to treat a certain disease (De Aquino et al., 2019).
Considering the relevance of the plant species found in the RENISUS list, we researched which were present in the studied area (Settlement 17 de Abril) and related them to their popular uses and associated scientific studies.
Of the 89 species found in the April 17 settlement, only three are listed in the RENISUS: Casearia sylvestris, Copaifera spp * (Copaifera langsdorffii) and Stryphnodendron adstringens.
Casearia sylvestris, popularly known as "guaçatonga", is used in folk medicine for purification and to treat diarrhoea, fever, rheumatism, skin disorders and snake bites (Table 1). Scientific studies report anti-ulcerogenic, anti-inflammatory, anti-tumour, anti-hyperlipidaemic, anti-coagulant, trypanocidal, leishmanicidal, anti-microbial, genotoxic, allelopathic, anti-hyperalgesic, antioxidant, phospholipase A2 inhibitory and anti-parasitic effects of leaves ( Table 2). The bark demonstrated anti-tumour activity (Table 2). Phytochemical studies report the presence of flavonoids in the leaves and aerial parts and terpenes in the leaves of this species (Table 2).
Copaifera langsdorffii is popularly known as "copaiba", and resin-extracted oil from its trunk is used by the population to treat inflammation, sore throat, urinary and pulmonary infections, and accelerate wound and ulcer healing (Table 1). Studies conducted on the leaves of this species report potential gastroprotective, anti-inflammatory and antifungal effects and significant genotoxicity (Table 2). Phytochemical studies reported the presence of galloquinquinic acids in the leaves. Oil extracted from the trunk, which is popularly used in folk medicine, has been shown in biological studies to induce cell cycle arrest and apoptosis, with a protective effect against colon carcinogenesis, cytotoxicity, embryotoxicity and bacteria ( Table 2). The seeds present immunomodulatory activity and the presence of xyloglucans and galloquinquinic acids (Table 2). Another part of this species is the fruits, which present antioxidant activity ( Table 2).
The barbed bark from Stryphnodendron adstringens, "barbatimão", is widely used in two different ways: externally for the treatment of uterine conditions, vaginal conditions, urinary tract infections, skin lesions, ulcers, inflammation, infections and skin infections; and internally for diarrhoea, throat inflammation, bleeding, scurvy, pulmonary complications, and respiratory infections. Additionally, internal use can be used to treat diarrhoea, sore throat, bleeding, scurvy, pulmonary complications, and respiratory infections (Table 1). Scientific studies have validated the popular indications, highlighting some biological activities in the stem bark of this species. Studies report trypanocidal, anti-fungal, antibacterial, antioxidant, anti-ulcerogenic, antigenic, anti-inflammatory and anti-mutagenic effects, as well as the presence of proanthocyanidins, flavonoids, prorobinetinidines and tannins ( Table 2).
The presence of these species demonstrates the importance of further scientific studies to prove their ethnopharmacological action against diseases, as well as ensuring secure access to and the rational use of medicinal and herbal plants, the development of technologies and innovations, the strengthening of chains and productive arrangements, the sustainable use of Brazilian biodiversity and the development of the Health Productive Complex.

Conclusion
This study provides 89 medicinal plants belonging to 39 families documented from the study area (reserve area of the settlement "17 April", MS, Brazil) for the first time. The most widespread traditional use, involves the treatment of gastro-intestinal system diseases (41 spp) and the most utilized parts were leaves (41%), justifying the conservation of biodiversity. Thus, future studies should be focused to establish the links between the traditional uses, active compounds and reported pharmacological activities. Additionally, three species are listed in the National Program for Medicinal and Phototherapeutic Plants (Casearia sylvestris, Copaifera langsdorffii and Stryphnodendron adstringens).