296 RBCIAMB | v.56 | n.2 | Jun 2021 | 296-304 - ISSN 2176-9478 A B S T R A C T Medicinal plants synthesize various secondary metabolites that can be used for therapeutic and antimicrobial purposes. In Brazil, the Unified Health System (SUS) offers several herbal medicines as an alternative in the treatment of various diseases. Considering the importance of these plants in the production of chemicals that expand therapeutic options and improve the health of SUS users, this review was carried out to quantitatively determine the antifungal activity of plants used as phytotherapeutics at RENAME. The selection of papers was performed at three distinct stages: examining and choosing titles related to antifungal action, reading the abstracts, and reading the whole selected articles. This review selected 22 studies of interest; 12 of them were conducted in Brazil and 10 were carried out in other countries. The papers chosen tested the growth inhibitory effect of plants against fungal species of agricultural and health importance, ranging from filamentous to yeast-like fungi, and Candida albicans was the most tested species. The growth of 39 fungal species were inhibited by some concentration of the extract used, with either an increase or decrease in antifungal activity depending on the extract used. The most frequently analyzed plant was the species Schinus terebinthifolius Raddi., studied in seven papers. The results found demonstrate the importance of analyzing medicinal plants and incorporating plant-based medicines in healthcare as an alternative source of treatment, highlighting the need for studies that evaluate the mechanisms action of their cytotoxicity and therapeutic effects in the human body. Keywords: herbal medicines; fungi; secondary metabolites. R E S U M O As plantas medicinais produzem uma série de metabólitos secundários que podem ser usados para fins terapêuticos e antimicrobianos. No Brasil, o SUS disponibiliza uma série de medicamentos fitoterápicos como alternativa ao tratamento de diversas enfermidades. Considerando a importância da utilização dessas plantas na produção de medicamentos que ampliem as opções terapêuticas e melhorem a atenção à saúde de usuários do sistema, elaborou-se este estudo de revisão com o objetivo de estimar quantitativamente a atividade antifúngica das plantas utilizadas como fitoterápicos contidas na RENAME. A seleção de artigos deu-se por meio de três etapas distintas: leitura e escolha de títulos relacionados à ação antifúngica, leitura dos resumos e leitura na íntegra dos artigos selecionados. Esta revisão selecionou 22 estudos de interesse, sendo 12 elaborados no Brasil e 10 em outros países. Os artigos escolhidos testaram a ação inibitória das plantas contra espécies de fungos de importância agrícola e sanitária, entre filamentosos e leveduriformes, sendo Candida albicans a espécie mais testada. Trinta e nove espécies foram inibidas por alguma concentração do extrato utilizado, havendo aumento ou diminuição da atividade antifúngica conforme substância extratora utilizada. A planta mais analisada foi a espécie Schinus terebinthifolius Raddi., estudada em sete artigos. Os resultados encontrados demonstram a importância da análise de plantas medicinais e da incorporação de medicamentos à base de plantas como fonte alternativa de tratamento, salientando a necessidade de estudos que demonstrem sua citotoxicidade e mecanismos de ação terapêutica no organismo humano. Palavras-chave: medicamentos fitoterápicos; fungos; metabólitos secundários. Medicinal plants of the Unified Health System (Sistema Único de Saúde) with antifungal potential Plantas medicinais do Sistema Único de Saúde com potencial antifúngico Mônica Jachetti Maciel1 , Claudete Rempel1 , Amanda Luisa Stroher1 , Patrícia Caye Bergmann1 , Diorge Jônatas Marmitt1 1Universidade do Vale do Taquari (Univates) – Lajeado (RS), Brazil. Correspondence address: Mônica Jachetti Maciel – Avenida Avelino Talini, 171 – Bairro Universitário – CEP: 95914-014 – Lajeado (RS), Brazil. E-mail: monicajm@univates.br Conflicts of interest: the authors declare that there are no conflicts of interest. Funding: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS). Received on: 04/22/2020. Accepted on: 08/31/2020 https://doi.org/10.5327/Z21769478766 Revista Brasileira de Ciências Ambientais Brazilian Journal of Environmental Sciences This is an open access article distributed under the terms of the Creative Commons license. Revista Brasileira de Ciências Ambientais Brazilian Journal of Environmental Sciences ISSN 2176-9478 Volume 56, Number 2, June 2021 http://orcid.org/0000-0002-6863-2181 http://orcid.org/0000-0001-8573-0237 http://orcid.org/0000-0003-4279-8279 http://orcid.org/0000-0003-0081-9158 http://orcid.org/0000-0001-5454-9099 mailto:monicajm@univates.br https://doi.org/10.5327/Z21769478766 http://www.rbciamb.com.br http://abes-dn.org.br/ Medicinal plants of the Unified Health System (Sistema Único de Saúde) with antifungal potential 297 RBCIAMB | v.56 | n.2 | Jun 2021 | 296-304 - ISSN 2176-9478 Introduction the set of chemical reactions performed by plants produces a series of substances called secondary metabolites, which include flavonoids, tannins, alkaloids, saponins, coumarins and quinones, also encom- passing the so-called essential oils or essences. These metabolites have various functions, which are related to the defense against animals, in- sects and other plants, protection from physical factors and attraction of animals for reproductive purposes (Simões et al., 2017; Tamariz-An- geles et al., 2018). In addition, many of these substances are important for characterizing and confirming the identity and quality of the plant in question, also manifesting antimicrobial activities, especially against bacteria, protozoa and fungi (Maciel et al., 2017). Several studies have shown the beneficial use of extracts and ac- tive principles extracted from plants against pathogens that can infect and cause harm to animals, humans and plant crops (Chansue, 2007; Itako et al., 2009; Marmitt et al., 2015a; 2015b; Pinho et al., 2012; Ro- drigues et  al., 2007). New antimicrobial assets derived from natural sources can decrease the amount of pesticides and other chemical products for environmental control applied on farms, reducing the risks to our health and to the environment. Hence, they become a safer — and often more effective — alternative than pesticides (Mauli et al., 2009; Schwan-Estrada et al., 2000). they can also be an alterna- tive to prevent many microorganisms from developing resistance to drugs used for their control, which increases the incidence of diseases caused by these pathogens and hampers the treatment of people af- fected (Cavalcanti et al., 2012; França et al., 2009; Maciel et al., 2017; Nogueira et al., 2008). In 2009, the National List of Medicinal Plants of Interest to SUS (RENISUS) was established. Consisting of 71 plant species with ther- apeutic potential according to traditional medicine knowledge, with the purpose of promoting the study of herbal medicines and their pro- duction in Brazil (Brazil, 2009a; 2009b). The provision of plant-derived medicines by the Brazilian public healthcare system began in 2007 through the National List of Essential Medicines (RENAME) (Brazil, 2017b), and currently comprises 12 plants: Aloe vera (L.) Burm.f., Cy- nara scolymus L., Glycine max (L.) Merr., Harpagophytum procumbens (Burch.) DC. ex Meisn., Maytenus ilicifolia Mart. ex Reissek, Mentha piperita L., Mikania glomerata Spreng., Plantago ovata Forssk, Rham- nus purshiana DC., Salix alba L., Schinus terebinthifolius Raddi, and Un- caria tomentosa (Willd. ex Schult.) DC.; offered in the form of syrups, tablets, capsules, gels, creams and dyes (Brazil, 2012; 2017a; 2017b). Considering the purpose for which RENISUS has been created, the aim of this systematic review was to show the amount of studies published on medicinal plants with antifungal activity as described in the national list of medicinal plants provided by SUS, using the CAPES (Coordination for the Improvement of Higher Education Personnel) Journals Portal as database, which encompasses publi- cations from several other platforms, such as SciELo, PubMed and Springer, among others. Materials and methods The present study used a systematic review of the literature as a technical procedure for gathering scientific information encompass- ing different cases, locations and perspectives from different research- ers, summarizing their objectives and results in a simplified manner (Greenhalgh, 1997; Carneiro; Takayanagui, 2009). The studies ad- dressed here were those concerning the antifungal potential of medic- inal plants provided as phytotherapeutics by SUS through RENISUS, and those with the full text available at the Capes Journals Portal in English, Portuguese or Spanish, were analyzed with no restrictions as to their publication year. Descriptors used were the scientific names of the plants (or phytotherapeutics) at RENAME and the term “antimi- crobial”, followed by the Boolean operator “and”, with no restrictions of language or publication year. The access link used was the one made available in the database. The titles of all the papers found when searching each species were read and the repeated ones were excluded, thus being counted only once. Review studies, interviews, reports, and studies on the practical use of plants or referring to their chemical constituents without either confirming or proving their antifungal effect were also excluded. A total of 10,763 articles were found in the initial search; 382 were reports and 267 were repeated scientific papers, and they were thus excluded from the study. Of all articles found in the initial search, 417 studies were selected to comprise the further stages of this review. The publications chosen were analyzed in three stages: first, by read- ing the title of all articles found in the database, and selecting those that included terms related to antifungals, such as “fungos”, “fungi”, “levedura”, “yeast”, “Aspergillus”, “Candida”, “Penicillium”, “Fusarium” and “antifúngico”, among others. A total of 67 studies were selected. Afterwards, the next stage consisted of reading the abstracts of the pa- pers selected in the first stage, which resulted in 32 papers selected. Those that somehow mentioned the method used and proved the an- tifungal effect of the studied plant were chosen. In the third and last stage, the papers selected in the second phase were completely read, to prove the antifungal effect of the plants of interest, and 22 studies were found to be compatible with the criteria established here, and were thus chosen to be included in the present review. The scientific names of the plants mentioned were written according to updated references for na- tive plants in Brazil (Reflora, 2010) and introduced plants (Taxonomic Name Resolution Service, 2020). During the search, a methodological adjustment was required to include the plant Glycine max. While using the same procedure adopted for the other plants, it was not possible to read the papers available starting on page 281 due to problems in the platform used for the search. To complete the search for this plant, restricting the publication year to 2009, the year in which RENISUS was created, was required. Only with this adjustment, was it possible to access all the studies published as of this date and the search for this descriptor was not complete. Maciel, M.J. et al. 298 RBCIAMB | v.56 | n.2 | Jun 2021 | 296-304 - ISSN 2176-9478 Results and Discussion After reading the 32 selected papers completely, 22 studies of interest were selected for inclusion in the present review, which corresponds to 5.3% of the total relevant papers initially found in the database. Chart 1 shows the total number of papers selected for each study of interest of each plant analyzed, followed by methodology and main results. Of the 12 plants that comprised this study, no studies on Maytenus ilicifolia, Salix alba and Rhamnus purshiana were selected, due to the fact that none of the papers found met the selection criteria. The papers were organized in a distribution chart by antifungal potential and therapeutic action (Chart 1). There were three publications in 2011, which was the year with the highest number of publications. The most recent research among the papers selected was from 2017, and the oldest was from 2002. Of the 22 selected studies, 12 (54.5% of the total) were conducted by Brazilian researchers (Biasi-Garbin et al., 2016; Braga et al., 2007; Duarte et  al., 2005; Freire et  al., 2012; Holetz et  al., 2002; Johann et  al., 2008; Martinelli et  al., 2017; Moraes et  al., 2015; Moura-Costa et  al., 2012; Schmourlo et  al., 2005; Santos et  al., 2010; Souza Júnior et  al., 2011), which indicates that the creation of RENISUS did promote medicinal plant studies in Brazil. Reports indicate that medicinal plants were already used in Europe in 460 B.C. in the form of hot and iced teas, moist compresses and dried herbs. They are still used today by many European countries as complementary medicines in the treatment of many diseases. Several other cultures have also relied on the properties of medicinal plants for thousands of years, with several species still in use to date (Van Wyk; Wink, 2018). Of the 22 selected articles in this study, nine (41%) were carried out in other countries, especially India and Iran, with two stud- ies each. The most tested plants in these studies were Mentha piperita, with 6 studies, and Cynara scolymus, with 2 studies. In the international scenario, studies on medicinal plants, espe- cially those focused on public health systems, have been disseminated since the First International Conference on Primary Health Care, held in 1978 in Russia (Gonçalves et  al., 2017). Heinrich (2010), studying medicinal plants worldwide, indicated an increase in the search for phytotherapeutics for the treatment of AIDS/HIV and viral diseases. In the same study, he points out that research has focused on the inno- vation of phytochemical studies for the isolation and identification of active ingredients. Since 1979, the World Health Organization has sug- gested the inclusion of complementary alternative medicine therapies in public health policies, with their use reaching 75% in France, 70% in Canada, and 42% in the USA (Zeni et al., 2017). Estimates indicate that 70–80% of drug development depends ex- clusively on plants, and much of the research in this area is focused on the isolation of plant active ingredients (Aslam; Ahmad, 2016). According to Rajeswara Rao and Rajput (2010), the major research areas on medicinal plants in the world are: development of technol- ogies for the cultivation and isolation of chemical compounds, im- plementation of quality control protocols, scientific validation of the traditional use of these plants, development of products using them as a production base, selection of markers for genotypes, creation of a DNA profile of the species studied, identification and isolation of enzymes and bioactive molecules, and screening of phytochemical compounds with antimicrobial properties. The nine international studies selected for this review were in vitro and 66.7% (6) also analyzed the chemical compounds present in the study plant, using chromatographic methods. None of them, however, identified the specific compound accounting for the anti- fungal activity observed. Of the international studies selected, seven (77.8%) were carried out after 2010, one of which was published in 2019. Compared to the Bra- zilian studies, where 58.3% were published in or after 2010, there was an increase in studies in this area at the global level after this period. In a comparative study, Assis et al. (2015) showed a strong growth trend in research on medicinal plants in analyzing 111 research groups between 1997 and 2010, a trend that has continued to intensify in later years. It is known that most medicinal plants are available in tropical countries (Dar et al., 2017). India and Iran stood out as the countries with the highest number of papers of interest, with two studies each (Desam et  al., 2019; Tyagi; Malik, 2011; Saharkhiz et  al., 2012; Mah- boubi; Kazempour, 2014), having an important diversity of plants rel- evant to the healthcare area (Panda et al., 2018; Tandon; Yadav, 2017; Sadat-Hosseini et al., 2017; Parsaei et al., 2016). The pharmacology of natural products allows determination of the bioactive compounds present in plants, that are responsible for growth-inhibitory effects. These bioactive compounds, also called sec- ondary metabolites, have antimicrobial effects due to their cytotoxicity, and because of their neuroactive effects, they can be used as analgesics, anesthetics and antidepressants, among others (Vizzotto et  al., 2010). As indicated by Piriz et al. (2014), medicinal plants have several benefi- cial properties that can be used for the benefit of humans. In their study, Piriz et al. (2014) found relevant results of studies on anti-inflammato- ry activity, especially in Brazil, which was the country with the highest number of papers published. The same number of papers produced in Brazil (12) was found in the present study, showing the importance and competence of Brazilian research demonstrated in this area. Marmitt et  al. (2015b), in a review, searched for plants with an- tibacterial effect in RENISUS, and found that 42% of the 19 selected published studies of interest were conducted in Brazil, thus indicating an increase in studies in the country after the creation of the National Policy on Medicinal and Herbal Plants (PNPMF). Similar results were found in the present study: of the 13 studies carried out in Brazil, 69% (9) were published after the creation of PNPMF. PNPMF (Brazil, 2006) has contributed to the increase in research aimed at the development of new plant-derived drugs, which are already used popularly in con- ventional medicine. Medicinal plants of the Unified Health System (Sistema Único de Saúde) with antifungal potential 299 RBCIAMB | v.56 | n.2 | Jun 2021 | 296-304 - ISSN 2176-9478 Plant species (Family) Part of the plant / compound / concentration used / treatment regimen (dose) Therapeutic activity Type of study Year of publication/ Journal/ Country Aloe Vera (Xanthorrhoeaceae) Gel from the mucilaginous part of the leaf plus potato dextrose agar (PDA) / Concentrations of 1, 5, 25, 50, and 100 mL/L Growth-inhibitory activity was detected at the lowest concentrations of the gel, which was effective against the fungi Penicillium digitatum and Botrytis cinerea In vitro 2010/ Postharvest Biology and Technology/ Spain Cynara scolymus (Asteraceae) Chloroform, ethyl acetate and butanol extract of dry leaves / Doses of 2.5, 5 and 10 mg/mL The butanol extract exhibited higher growth-inhibitory activity and was the only one capable of preventing the growth of Candida lusitaniae and Mucor mucedo In vitro 2004/ Journal of Agricultural and Food Chemistry/ China Cynara scolymus (Asteraceae) Extract of powder from dry leaves with ethanol at the concentrations 25, 50, 75 and 97% v/v, 50% methanol, and pure water / Concentrations from 2.5 to 20 mg/mL The 75 and 97% ethanol extracts proved to have the highest activity against strains of Candida albicans Candida sp. In vitro 2011/ Tropical Journal of Pharmaceutical Research/ Romania Mentha piperita (Lamiaceae) 40 g of fresh plant parts to obtain the essential oil, using 50 mL of dichloromethane for extraction / Dose of 2–0.03 mg/mL It showed moderate activity (MIC of 0.6 mg/mL) in the control of Candida albicans strains In vitro 2005/ Journal of Ethnopharmacology/ Brazil Mentha piperita (Lamiaceae) Dried seed extract obtained using 95% ethanol / Concentrations of 50, 25, 12.5, and 6.25 mg/mL / Dose 1 mg/mL The extract could inhibit Aspergillus niger and Candida albicans with MIC of 5 mg/mL In vitro 2006/ Biology/ Turkey Mentha piperita (Lamiaceae) Hydrodistilled extract of leaves (1:7 w / v), extracted using dichloromethane (5:1 v/v) / Concentration 0.1-0.2% (v/v) The essential oil inhibited the growth of Aspergillus flavus, Aspergillus glaucus, Aspergillus niger, Aspergillus ochraceous, Colletotrichum gloeosporioides, Colletotrichum musae, Fusarium oxysporum, and Fusarium semitectum In vitro 2011/ Journal of Food Safety/ Brazil Mentha piperita (Lamiaceae) Essential oil extracted using ethanol and diethyl ether / Concentrations of 0.14–18 mg/mL / Doses of 10–40 μL The extract was effective against Aspergillus flavus, Aspergillus niger, Mucor spp., Fusarium oxysporum, Candida albicans, and Saccharomyces cerevisiae, and its highest efficacy was against Penicillium digitatum In vitro 2011/ Food Control/ India Mentha piperita (Lamiaceae) Hydrodistillation of aerial parts during flowering / at 1:50 and 1:1,000 dilutions The oil could inhibit Cryptococcus neoformans, Aspergillus flavus, Aspergillus fumigatus, Aspergillus oryzae, Aspergillus clavatus. It also completely inhibited biofilm formation by Candida albicans and Candida dubliniensis In vitro 2012/ International Scholarly Research Network/ Iran Mentha piperita (Lamiaceae) Extraction of essential oil by hydrodistillation of the aerial parts of the plant at the beginning of flowering / Concentrations of 16–0.25 μg/mL The oil exhibited antimicrobial activity against strains of Candida albicans, Candida glabrata, and Aspergillus niger In vitro 2014/ Songklanakarin Journal of Science and Technology/ Iran Chart 1 – Antifungal potential and therapeutic action of medicinal plants evaluated in the studies of interest selected. Continue... Maciel, M.J. et al. 300 RBCIAMB | v.56 | n.2 | Jun 2021 | 296-304 - ISSN 2176-9478 Continue... Plant species (Family) Part of the plant / compound / concentration used / treatment regimen (dose) Therapeutic activity Type of study Year of publication/ Journal/ Country Mentha piperita (Lamiaceae) Hydrodistillation of dry leaves to obtain the extract dissolved in 95% ethanol / Concentrations of 4, 2, 1, 0.5, 0.25, 0.125 μL/mL It prevented the growth of Microsporum canis, Epidermophyton floccosum, Trichophyton rubrum, and Trichophyton mentagrophytes at concentrations of 2.0 and 4.0 μL/mL In vitro 2015/ Environmental Health and Preventive Medicine/ Egypt Mentha piperita (Lamiaceae) Hydrodistillation at 1:5 concentration / dose of 1 μL The essential oil exhibited strong antifungal activity against Alternaria, Penicillium spp., Fusarium oxysporum, Fusarium tabacinum, Aspergillus fumigatus, Candida albicans, Cladosporium herbarum, and Rhizoctonia solani In vitro 2017/ Journal of King Saud University/ India Mikania glomerata (Asteraceae) Lower parts of the plant were macerated with water and ethanol (90–10%) / Dose of 2 mg/mL It exhibited moderate activity (MIC of 100–500 μg/mL) against Candida krusei and Candida parapsilosis In vitro 2002/ Memórias do Instituto Oswaldo Cruz/ Brazil Mikania glomerata (Asteraceae) 40 g of fresh parts of the plant were used to obtain the essential oil, using 50 mL of dichloromethane for extraction / Dose of 2-0.03 mg/mL It exhibited weak inhibitory activity (MIC > 2.0 mg/mL) compared to Candida albicans In vitro 2005/ Journal of Ethnopharmacology/ Brazil Schinus terebinthifolius (Anacardiaceae) Aqueous-ethanol extract (20:3 mg/mL) from the aerial parts / Concentration of 1 mg/mL The aqueous extract was able to prevent the growth of Candida albicans In vitro 2005/ Journal of Ethnopharmacology/ Brazil Schinus terebinthifolius (Anacardiaceae) Methanol extract (3:2,000) / Dose of 100 mg/mL It exhibited antifungal activity against Candida albicans and Cryptococcus neoformans In vitro 2007/ Journal of Ethnopharmacology/ Brazil Schinus terebinthifolius (Anacardiaceae) Oil extraction from leaves with 80% ethanol and addition of water, hexane, dichloromethane and ethyl acetate / Concentrations from 1,000 to 7.8 μg/mL The ethyl acetate extract portion exhibited higher antifungal activity against strains of Candida albicans In vitro 2008/ World Journal of Microbiology and Biotechnology/ Brazil Schinus terebinthifolius (Anacardiaceae) Extract obtained by hydrodistillation / Concentrations of 25, 50, 75 and 100% / Dose of 100 μL/mL The 25% dilution was able to inhibit the growth of Colletotrichum sp., Alternaria spp. and Botrytis spp. Fusarium spp. was only inhibited by the 50% dilution In vitro 2010/Revista Brasileira de Farmacognosia/ Brazil Schinus terebinthifolius (Anacardiaceae) Hydroalcoholic extract of the bark (1:10) / Dose of 2 mg/mL It exhibited inhibitory activity against strains of Candida tropicalis and Candida parapsilosis In vitro 2012/ Journal of Ethnopharmacology/ Brazil Schinus terebinthifolius (Anacardiaceae) Aqueous, ethanol and acetone extracts / Concentrations from 1,000 to 1.95 μg/ mL / Dose of 2,000 μg/mL Ethanol extract exhibited strong activity against Trichophyton rubrum and Trichophyton mentagrophytes In vitro 2016/Revista do Instituto de Medicina Tropical de São Paulo/ Brazil Chart 1 – Continuation. Medicinal plants of the Unified Health System (Sistema Único de Saúde) with antifungal potential 301 RBCIAMB | v.56 | n.2 | Jun 2021 | 296-304 - ISSN 2176-9478 Source: Castillo et al. (2010), Ertürk (2006), Ibrahim and El-Salam (2015), Vamanu et al. (2011) and Zhu et al. (2004). Plant species (Family) Part of the plant / compound / concentration used / treatment regimen (dose) Therapeutic activity Type of study Year of publication/ Journal/ Country Schinus terebinthifolius (Anacardiaceae) Dichloromethane and oleoresin extract / Concentrations of 1–0.05% Oleoresin and the extract exhibited moderate activity against strains of Candida albicans and Penicillium sp. In vitro 2017/ Ciência Rural/ Brazil Uncaria tomentosa (Rubiaceae) Hydroalcoholic extract 70% of the stem in a 1:1 ratio / Concentrations at 1:512 dilution It exhibited strong activity against the strains of Candida albicans, Candida krusei, Candida tropicalis, Candida guilliermondii up to 1:16 dilution In vitro 2011/ Pesquisa Brasileira em Odontopediatria e Clínica Integrada/ Brazil Uncaria tomentosa (Rubiaceae) Hydroethanolic extract (50% v/v) / Concentration of 1 mg/mL It exhibited strong activity against the resistant species Candida krusei and Candida glabrata In vitro 2015/ Industrial Crops and Products/ Brazil Chart 1 – Continuation. Different numbers of papers were found for each plant species se- lected, indicating a variety and effectiveness of different mechanisms of action in each species. The therapeutic activity shown is related to the extraction method and dose used. Extraction using aqueous-ethanol solvents afforded higher growth-inhibitory activity (27 different strains growth-inhibited), followed by extraction of essential oils using hydrodis- tillation (22 different strains growth-inhibited) and extraction using di- chloromethane (12 different strains growth-inhibited). Different solvents extract different active principles from the plant, which are responsible for the effects caused by the use of medicines containing these substances (e.g., anti-inflammatory, hypoglycemic, anticoagulant and antiplatelet ac- tivities) (Sixel; Pecinalli, 2005). Studies show that the use of the crude extract, shows a considerably higher bioactivity than using each active principle separately (Sixel; Pecinalli, 2005). The studies analyzed in this review, therefore, showed higher antimicrobial activity, since all the assays were performed us- ing crude extracts. Among all the plants analyzed, approximately 54% (12) showed growth-inhibition in all of the fungal species tested, and 41% (9) at least prevented the growth of 50% of the species analyzed. The butanol extract of Schinus terebinthifolius was tested against Can- dida neoformans, Candida albicans, and Trychophyton rubrum, and in- hibited only Candida albicans strains. Analyzing the data obtained, Candida albicans was the most tested microorganism in all papers selected, totaling 16 studies analyzing extracts and oils against strains of this species. Overall, 18 studies (78.3% of the total) analyzed seven Candida species regarding their sensitivity to medic- inal plant extracts and oils. Filamentous fungi were also part of the selected studies. Nine species of Aspergillus were used in seven articles (39.2% of the total), and Aspergillus niger was most studied, appearing in six papers. According to Correia et  al. (2006), the family Anacardiaceae is rich in bioactive compounds that may have antimicrobial effects, with the genus Schinus being among the 11 most studied in this fam- ily. Correia  et  al. (2006) demonstrated the presence of phenolic lip- ids in this plant. These compounds have amphipathic characteristics, which facilitate their penetration into the plasma membrane, causing changes in their structure and properties. Therefore, seven of the 22 studies selected for this review analyzed the bioactive and antimicro- bial activity of Schinus terebinthifolius, which prevented the growth of 78% (14) of the 18 strains tested. Another important factor, pointed out by Gobbo-Neto and Lopes (2007), indicates that changes in the concentrations of active com- pounds may occur due to circadian cycle (day/night), seasonality, plant age, development period, temperature, attack by pathogens, pollution, and the hormonal development process in the plant. Evans (2009) showed significant differences in the presence of chemical compounds during winter and summer. Vasconcelos Silva et al. (1999) demonstrat- ed how the circadian cycle affects the production and concentration of bioactive substances, showing high quantitative contrasts at different times of the day. Stress caused by temperature variations can also affect the con- centrations of these compounds, as indicated by Christie et al. (1994). Plant age is also related to these changes. Flowering period leads to increase or decrease in certain substances, as well as the period of leaf emergence or loss in deciduous plants. This indicates why the same plant species had different results in this paper. Two studies carried out with Mentha piperita (Mahboubi; Kazempour, 2014) (Saharkhiz et al., 2012) used Aspergillus flavus samples to test the antimicrobial action of essential oils extracted using hydrodistillation. The first study used the Maciel, M.J. et al. 302 RBCIAMB | v.56 | n.2 | Jun 2021 | 296-304 - ISSN 2176-9478 aerial parts at the beginning of flowering to obtain essential oils and observed excellent growth-inhibitory activity. However, the second study, which also used aerial parts to extract essential oils, although after the beginning of flowering, found no growth-inhibitory action at any concentration in Aspergillus flavus strains. The same occurred in studies carried out by Schmourlo et  al. (2005) and Biasi-Garbin et  al. (2016), who tested the action of the ethanol extract of the species Schinus terebinthifolius. The extract was prepared using different parts of the plant in each study, dif- fering only in the concentration used (Chart 1). At the end of the study, Biasi-Garbin et  al. (2016) were able to inhibit the growth of the pathogenic fungus Trichophyton rubrum, while Schmourlo et al. (2005) showed no effect on this fungus. Schmourlo et al. (2005) and Braga et  al. (2007) conducted a study with the same plant species using extracts against Candida neoformans strains. Alcoholic extracts were obtained for both studies; Schmourlo et al. (2005) used ethanol as extraction solvent and Braga et  al. (2007) used methanol. In the first study, the extract did not prevent the growth of Candida neofor- mans, while it was inhibited in the second study, thus indicating that different solvents affect the composition of bioactive substances, ei- ther intensifying or preventing the effect of the extract, as already ob- served by Silva (2010). Silva (2010) compared different extracts of es- sential oils, classifying the different activities exhibited by each extract. Thus,  he identified significant differences in the action of different solvents, related to solubility and affinity with the plasma membrane of the strains he compared. Conclusion Of the 417 papers initially read, 22 that demonstrated an antifungal effect were selected for the present review. The two plants that exhibited the highest antifungal activity were Mentha piperita, with eight studies, and Schinus terebinthifolius, with seven studies. Candida albicans was the most frequently tested fungal species, as it was present in  11 dif- ferent studies. Other species of the genus Candida were tested  in 10 different studies. The genera Fusarium and Aspergillus also stood out, with five and 13 studies, respectively. The incorporation of integrative and complementary practices within the scope of SUS through PNPMF helps to understand and per- ceive the importance of studies on this topic. RENAME has also played an important role in the increase and constant evolution of the research on herbal medicines in Brazil, especially after their inclusion in SUS. There is a therapeutic equivalence between essential oils and ex- tracts used to obtain active ingredients. 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