Essential Oils from Native Brazilian Plants of the Genus Eugenia as an Innovative and Sustainable Source of Active Ingredients for Food Systems and Human Health and Well-Being

: Brazil is home to some of the world’s greatest biodiversity, providing an immeasurable number of new opportunities and unexplored sources of native plants for the development of products, extracts, foods, and compounds of social and economic interest. Among these, plants of the genus Eugenia stand out because of the large number of species found in Brazilian territory, many of which are endemic and exclusive to Brazil. These plants have emerged as potential sources for obtaining essential oils with relevant biological activities. In this context, the present review provides an overview of essential oils derived from the main native plants of Brazilian socio-biodiversity from the genus Eugenia with food value ( Eugenia stipitata , Eugenia dysenterica , Eugenia involucrata , Eugenia brasiliensis , Eugenia klotzschiana , Eugenia uniflora , and Eugenia pyriformis ) and their phytochemical profile and health beneficial effects. The compiled data showed that the essential oils of these plants are composed mainly of sesquiterpenes and, in smaller quantities, monoterpenes and other compounds. These compounds contribute to different biological activities, including antimicrobial, antioxidant, anticancer, and antiparasitic effects. These findings demonstrate that the essential oils of Brazilian native plants of the genus Eugenia can be a promising raw material for active ingredients to develop innovative and sustainable food products, drugs, and cosmetics


Introduction
Uncontrolled urban growth has been the subject of constant discussion worldwide because of its growing detrimental impact on social, environmental, and economic sectors.Therefore, adopting environmentally responsible development approaches aiming to conserve resources, protect ecosystems, and promote long-term well-being for both humans and the planet is of vital importance to meet the needs of the current society without compromising the ability of future generations to meet their own needs [1,2].In this regard, stemming from the continuous efforts of the United Nations, in 2015, its members adopted "The 2030 Agenda for Sustainable Development", which contains 17 Sustainable Development Goals (SDGs).These objectives provide a comprehensive framework to guide policies and practices at all levels, aiming to ensure that economic, social, and environmental development is achieved in an integrated and equitable manner, to attain an eco-friendly world for everyone [3,4].
The preservation of biological diversity is one of the fundamental aspects to ensure sustainable development since it is essential for ecosystem health and offers multiple benefits to humanity [1].Brazil is recognized for harboring some of the greatest biodiversity in the world, comprising approximately 15-20% of global biological diversity.This immense biodiversity is due to the presence of many ecological biomes that provide specific conditions for the development of different species.Thus, the Brazilian territory represents an available and unique source to explore and discover food species and active principles with the potential to improve people's health and well-being [1,5].However, the expansion of agriculture and urbanization has promoted a growing destruction of natural areas in Brazilian biomes.Consequently, many plant species may disappear even before being cataloged and studied.Therefore, it has become urgent to investigate and rediscover the richness of Brazil's natural heritage to protect it and build a more sustainable future [1].
Recent studies have evidenced the action of different native Brazilian plants in the prevention and treatment of non-communicable chronic diseases, including cancer, cardiovascular diseases, diabetes, obesity, and metabolic syndrome, among others [6,7].Thus, native Brazilian plants emerge as strategic key ingredients for developing high-valueadded products, such as functional foods, nutraceuticals, drugs, and cosmetics.Among the numerous plant species with exploratory potential, plants belonging to the genus Eugenia stand out as the largest genus in terms of species within the family Myrtaceae, with more than 1000 species scattered around the world, 414 of which are found in Brazilian territory, with 300 being endemic and exclusive to Brazil [8].
Native Brazilian plants and fruits belonging to the genus Eugenia are rich in biologically active compounds (e.g., phenolic compounds, carotenoids, vitamins, fibers, sugars, and volatile compounds, among others) with therapeutic effects, delaying the onset and/or development of some diseases such as diabetes, cancer, and obesity [9,10].Among the genera belonging to the family Myrtaceae, the genus Eugenia stands out as the fourth most important genus in essential oil production, trailing only behind the genera Eucalyptus, Melaleuca, and Psidium.Essential oils from Eugenia species are highly complex natural mixtures.Studies conducted on these essential oils have already identified approximately 300 compounds, with a predominance of cyclic sesquiterpenes and lesser amounts of monoterpenes.Additionally, aromatic and aliphatic compounds can be found in a few species.Essential oils derived from these plants and their terpenoid compounds have versatile applications in different industrial sectors such as food, pharmaceutical, and cosmetics [11].Several studies have demonstrated that essential oils from Eugenia species and their phytochemicals exert a range of biological activities, including antioxidant, anticancer, anticholinesterase, antiviral, antimicrobial, antiparasitic, and insecticidal activities [12,13].
The biological properties of essential oils from native Brazilian plants belonging to the genus Eugenia have stimulated the interest of researchers, industries, producers, and consumers.Thus, the essential oils of these plants can be sources of opportunities to produce innovative products, protecting biodiversity and the environment, fostering economic development, and improving public health and well-being, contributing significantly to sustainable development by meeting at least three United Nations SDGs including SDG 3 (good health and well-being), SDG 9 (industry, innovation, and infrastructure), and SDG 12 (responsible consumption and production).
From this perspective, we summarize the most recent scientific data available in the literature regarding the chemical composition and biological properties of essential oils from native Brazilian plants belonging to the genus Eugenia with food value, aiming to stimulate the production of innovative and eco-friendly products as a strategy for promoting health and well-being.Thus, this review can serve as reference material to support researchers and industries in the development of innovative and sustainable products derived from Brazilian biodiversity to help achieve the mentioned SDGs.

Search Strategy and Study Selection
In the current literature review, we performed a search strategy to find data regarding the chemical composition and biological properties of essential oils from native Brazilian plants of the genus Eugenia.The identification of plant species to be included in this review was conducted by consulting the 2021 official list of native plants of Brazilian socio-biodiversity with food value from the Ministérios da Agricultura, Pecuária e Abastecimento e do Meio Ambiente (MAPA/MMA) [14].From this official list, seven plant species belonging to the genus Eugenia were found (for more details regarding the popular names, scientific names, natural geographic distribution, and use for food purposes of these species, refer to Table 1).After identifying the species, this review was initiated by electronic searching using the main repositories of the world's scientific data (Scopus, Google Scholar, Science Direct, Web of Science, Scielo, and PubMed databases) to gather relevant articles published in scientific journals in the last decade (2014 to the present).We used the following terms to perform our bibliographic search: "Eugenia stipitata" OR "Eugenia dysenterica" OR "Eugenia involucrata" OR "Eugenia brasiliensis" OR "Eugenia klotzschiana" OR "Eugenia uniflora" OR "Eugenia pyriformis" AND "essential oil".The abovementioned terms were searched for in the article title, abstract, and keywords.The search was not restricted to any specific language.The articles retrieved from the databases were selected for a full-text review.Inclusion and exclusion criteria were determined by the authors to avoid biases in the selection of articles.Inclusion parameters included articles that reported results concerning essential oil, chemical composition, and biological properties.Meanwhile, exclusion parameters included duplicates, publications before 2014, theses, editorials, communications, and conference abstracts.
Table 1.The official list containing general information about native species of the Brazilian sociobiodiversity from the genus Eugenia with food value a .pene hydrocarbons and their oxygenated derivatives, along with other compounds like phenylpropanoids, aldehydes, esters, alcohols, and ketones, present in low amounts [15].These compounds are different secondary metabolites produced by plants, which play an important role in defense mechanisms against herbivores, pathogens, and environmental stressors [17].Additionally, the volatile compounds present in essential oils possess various biological properties related to human health, including antioxidant, anti-inflammatory, antimicrobial, anticancer activities, and others [18][19][20].
The 10 most abundant compounds found in the essential oils from Brazilian native Eugenia species with food value are listed in Table 2. Additionally, the plant part used, the extraction method, the percentage yield, the total number of identified compounds, and the total identified area of essential oils are provided.These native Eugenia species are distributed in several Brazilian biomes; therefore, the essential oils of these plants have more than 80 compounds in their composition.The sesquiterpene hydrocarbons (e.g., germacrene A, germacrene B, germacrene D, α-humulene, β-caryophyllene, β-elemene, γ-elemene, δ-cadinene, and bicyclogermacrene) and their oxygenated derivatives (e.g., atractylone, curzerene, selina-1,3,7(11)-trien-8-one, selina-1,3,7(11)-trien-8-one epoxide, germacrone, globulol, spathulenol, viridiflorol, caryophyllene oxide, and α-cadinol) are commonly found.However, monoterpene hydrocarbons (e.g., αpinene, limonene, γ-terpinene, and p-cymene) and their oxygenated derivatives (e.g., 1,8cineole), and other classes of compounds, such as phenylpropanoids, are also present, albeit in smaller proportions, contributing to the complexity and uniqueness of the essential oils of these Brazilian native plants.The chemical structures of the volatile compounds most frequently found in the essential oils of native Brazilian Eugenia species are shown in Figure 1.
The chemical profile of the essential oils obtained from the dried leaves of E. stipitata consists mainly of sesquiterpene hydrocarbons and their oxygenated derivatives such as germacrene D (11.8%), (Z)-α-bisabolene (8.4%), and cadin-4-en-10-ol (6.1%) [23].Additionally, other authors have found different compositions of the essential oil from E. stipitata leaves [21,22,24].For example, Costa et al. [24] obtained compounds such as β-eudesmol (15.28%), γ-eudesmol (10.85%), and elemol (10.21%).Meanwhile, Rivera et al. [21] found γ-muurolene (22.34%), β-caryophyllene (12.11%), and α-copaene (5.20%) as their major compounds.Similarly, sesquiterpene hydrocarbons and their oxygenated derivatives are the most abundant compounds for essential oils obtained from E. involucrata leaves.Toledo et al. [30] noticed that approximately 50% of the total identified area of essential oil from dried leaves of E. involucrata was composed of elixene (26.53%), β-caryophyllene (13.16%), and α-copaene (8.41%).Another study with dried leaves of E. involucrata found that around 50% of the identified compounds were represented by germacrene B (22.17%), bicyclogermacrene (19.76%), and β-elemene (10.86%) [29].On the other hand, besides sesquiterpenes and their derivatives, monoterpenes can be found abundantly in the essential oils from E. dysenterica leaves.For example, Galheigo et al. [25] found the monoterpene (Z)-β-ocimene (19.14%) to be the most abundant compound present in the essential oil from fresh leaves of E. dysenterica, followed by sesquiterpenes (β-caryophyllene (15.36%) and caryophyllene oxide (8.23%)).Another study reported the presence of monoterpene limonene (16%) as the most abundant compound in the essential oil from dried leaves of E. dysenterica [28].These differences in the composition of essential oils can also be observed for the other plants studied, such as E. brasiliensis, E. klotzschiana, E. uniflora, and E. pyriformis (Table 2).Several factors highly influence the diverse composition of essential oils, including the type of corresponding family/genus, plant part, time and period of harvesting, physiological age and stage of development of the plants, geographical and climatic conditions, post-harvest drying, plant storage conditions, and extraction methods, among others [58,59].As demonstrated in Table 2, it can be observed that the species and the part of the plant used contributed to obtaining different profiles of essential oils.dos Santos et al. [33] identified that β-caryophyllene (7.70%), spathulenol (6.42%), and δ-cadinene (5.55%) were As demonstrated in Table 2, it can be observed that the species and the part of the plant used contributed to obtaining different profiles of essential oils.dos Santos et al. [33] identified that β-caryophyllene (7.70%), spathulenol (6.42%), and δ-cadinene (5.55%) were the most abundant compounds in the essential oil obtained from dried leaves of E. brasiliensis.In comparison, the essential oil from E. uniflora leaves was predominantly composed of germacrone (37.82%), curzerene (16.60%), and germacrene B (13.54%).Carneiro et al. [34] identified several common compounds in essential oils obtained from the fresh leaves and flowers of E. klotzschiana (e.g., β-elemene, spathulenol α-cadinol, globulol, γ-selinene, α-humulene, γ-elemene, and α-copaene), while others were found exclusively in the leaves (e.g., caryophyllene oxide and τ-muurolol) or flowers (e.g., germacrene D, α-caryophyllene, α-farnesol, γ-gurjunene, eugenol, and ledene oxide).Besides the profile difference noted among the essential oils obtained from different parts of E. klotzschiana, it was observed that the major compounds also changed.The essential oil from the fresh flowers was mainly composed of germacrene D (29.90%), γ-elemene (12.06%), and α-caryophyllene (10.14%), whereas the essential oil from the fresh leaves was predominantly composed of β-elemene (10.65%), spathulenol (8.76%), and caryophyllene oxide (7.44%).Additionally, the method used to obtain an essential oil affects the diversity and quantity of these compounds.It is noted in Table 2 that hydrodistillation is the most commonly employed method to obtain essential oils from native Brazilian Eugenia species, while few studies use the steam distillation method.Additionally, a variation in extraction time (1 to 6 h) can be observed.These different methods may result in significant variations in the composition and yield of the essential oils.In this review, only one study was found that evaluated the effect of hydrodistillation time on the yield of essential oils from fresh leaves of E. pyriformis [54].
In addition to the factors described above, different drying methods, the age of the leaves used, and the specimens also affect the composition of essential oils.For example, Carneiro et al. [34] found variations in the composition of essential oils from E. klotzschiana leaves before and after different drying methods (shade or kiln drying), where αcaryophyllene was not found in fresh leaves but became the major compound after drying.Similarly, an increase in the content of other compounds was observed after the drying processes, including γ-elemene (1.5 to 5.5-fold), where kiln drying led to a more significant increase.On the other hand, there was a reduction in the content of β-elemene by almost 90% after the drying process.Assis et al. [51] observed an 11.83% increase in sesquiterpenes of essential oils from E. uniflora leaves when dried at 45 • C compared with room temperature (22 • C).Santos et al. [41] verified that the age of the E. uniflora leaves resulted in different compositions of essential oils.The authors identified that germacrone was present only in young leaves, representing about 38% of the total composition of the essential oil, while curzerene was predominant in mature leaves (around 22%).Additionally, furanodiene was identified in large quantities only in mature leaves, accounting for 19%.Figueiredo et al. [46] studied the essential oils obtained from the leaves of five E. uniflora specimens.They observed that curzerene was not detected in specimens 1, 2, or 3, while in specimen 4, this compound accounted for around 50% of the identified compounds.On the other hand, compounds selina-1,3,7(11)-trien-2-one (18.1-32.6%)and selina-1,3,7(11)-trien-2-one epoxide (16.0-30.4%)were the majority for specimens 1, 2, and 3, while they were not found in specimens 4 or 5. Cipriano et al. [52] examined the composition of essential oils obtained from leaves of 36 different E. uniflora genotypes.Through the cluster analysis method, they classified these essential oils into six groups according to their different chemical compositions.Selina-1,3,7(11)-trien-8-one, selina-1,3,7(11)-trien-8-one epoxide, curzerene, germacrone, 7-epi-α-selinene, furanodiene, and 7,14-anhydro-amorpha-4,9-diene were the key components that differentiated the groups.Ramalho et al. [53] investigated the variability in the composition of essential oils in E. uniflora fruits from three fruit biotypes (red, red-orange, and purple) and at different stages of ripeness.The constituents were subjected to multivariate analysis, and the fruit samples were differentiated by selina-1,3,7(11)-trien-8-one (36.06-41.22%),and selina-1,3,7(11)-trien-8-one epoxide (19.36-34.28%)for the red-orange biotype, curzerene (14.41-15.75%)and atractylone (6.90-10.10%)for the red biotype, and germacrone (51.56-56.80%)and spathulenol (5.46-8.36%)for the purple biotype.Furthermore, as other studies report, climatic influence and seasonality affect the content and composition of essential oils from native Brazilian Eugenia species.For example, Luz et al. [49] found significant variations in the total area identified of essential oils from E. uniflora leaves in rainy and dry periods (99.98% and 95.06%, respectively).Although major compounds remained the same during these periods (curzerene, germacrone, and β-elemenone), some other compounds were found only in the rainy season (e.g., γ-elemene and δ-elemene) or in the dry season (e.g., humulene).Siebert et al. [31] observed that spathulenol was the major compound found in essential oil from E. brasiliensis leaves from the spring (16.02%) and summer (18.17%), and τ-cadinol (12.83%) in essential oil from the autumn, both sesquiterpene compounds.On the other hand, they found α-pinene (15.94%), a monoterpene, to be the major compound in essential oil from the winter.Monoterpenes are smaller molecules, which allows them to be retained in the plant in more humid and colder climates, possibly explaining their higher content in winter essential oils [31].
Therefore, essential oils from native Brazilian Eugenia species demonstrate a profound complexity in their composition due to the series of factors previously discussed.These include the botanical species, the specific part of the plant used, the stage of maturation, the season, the climatic conditions, and the drying and extraction methods.Consequently, a more comprehensive understanding of the determinants that shape the profile and composition of these essential oils is needed.This knowledge guarantees the quality, efficiency, and sustainability of production processes and reveals new ways of using and applying these valuable natural reservoirs.

Biological Activities of Essential Oils
As seen in the section above, essential oils from Brazilian native plants of the genus Eugenia exhibit a complex mixture of phytochemicals in varying concentrations, including terpenes, terpenoids, and aromatic and aliphatic components.The presence of these compounds may contribute to the wide range of health benefits associated with essential oils.Essential oils from Brazilian native plants have been used for centuries in folk medicine for treating various pathologies and promoting health and well-being.Consequently, many recent studies have been conducted to validate the effects reported by folk medicine and identify other biological activities and therapeutic effects of these essential oils.In the sections below, we present and discuss the main biological activities reported for essential oils obtained from native Brazilian Eugenia species, highlighting the identification of biological targets and potential mechanisms of action.

Antimicrobial Activity
Food spoilage microorganisms, such as bacteria, yeasts, and fungi, contribute to annual food losses reaching up to 40%.Additionally, foodborne pathogenic microorganisms are a constant public health concern because of the various disorders they can cause [60].Several in vitro studies have demonstrated that essential oils obtained from native Brazilian Eugenia species exhibit antimicrobial activity against food spoilage and pathogenic microorganisms (see Table 3).• Gram-positive bacteria (MIC 125 to >1000 µg/mL) and S. aureus (MIC 125 to 250 µg/mL) were the most sensitive.

•
Gram-negative bacteria and yeast were more resistant (MIC ≥ 1000 µg/mL). [56] Aerial parts (leaves and twigs) Malassezia furfur The antimicrobial activity of essential oils is attributed to several cellular mechanisms and is related to their composition [50].The main characteristic demonstrating the antimicrobial potential of essential oils lies in the hydrophobic character of their compounds [63].These compounds play a crucial role in disrupting the lipid membranes of microbial cells, making them permeable and causing the leakage of intracellular constituents, such as ions, glucose, and ATP, resulting in microbial death [63,64].These oils also have the ability to interfere with enzymatic systems involved in energy production and the synthesis of structural compounds [30,63].
The antimicrobial activity of essential oils obtained from native Brazilian Eugenia species has been evaluated in vitro for a myriad of foodborne and oral microorganisms, mainly bacteria, yeast, and fungi (Table 3).Among these, essential oil from E. uniflora stands out as the most commonly investigated, which could be related to its higher bioavailability in different Brazilian regions and pleasant aroma and properties [10].Additionally, most studies prioritize evaluating the activity of essential oils from plant leaves (Table 3), while some authors have also evaluated the essential oils from other plant parts, such as twigs [57] and flowers [34].This is associated with the high content of aromatic compounds present in leaves, their ease of harvesting, consistency in their chemical composition, and their historical use [64].
Regarding the in vitro methods commonly applied for antimicrobial screening of essential oils from native Brazilian Eugenia species, the determination of the minimum inhibitory concentration (MIC) using broth dilution methods has been the most applied, while some studies further determined the minimal bactericidal concentration (MBC) and/or the minimum fungicidal concentration (MFC) of the essential oils (Table 3).The MIC represents the lowest concentration of an essential oil required to inhibit the growth of microorganisms under certain conditions, while the MBC and MFC refer to the lowest concentration of an essential oil that results in the inactivation of the majority (usually ≥99.9%) of bacterial and fungal populations, respectively [65].
In the following sections, the main results derived from research on the antimicrobial effects of essential oils from native Brazilian Eugenia species are described.

Antimicrobial Activity against Bacteria
As seen in Table 3, essential oils from native Brazilian Eugenia species have been evaluated for their antimicrobial effectiveness against both collection bacterial strains and clinical and food isolates.The in vitro activity of essential oils from native Brazilian Eugenia species has been frequently tested against foodborne bacterial pathogens, mainly Grampositive bacteria including Staphylococcus aureus, Bacillus subtilis, and Listeria monocytogenes and Gram-negative bacteria including Escherichia coli, Salmonella spp., and Pseudomonas aeruginosa (Table 3).These bacteria are frequently studied because of their prevalence in food contamination and their significant impact on food safety and public health [63].On the other hand, the oral bacteria most commonly exposed to essential oils from native Brazilian Eugenia species in in vitro tests are Streptococcus salivarius, Streptococcus mutans, Streptococcus mitis, Streptococcus sanguinis, and Streptococcus sobrinus.These bacteria play an important role in dental caries, periodontal diseases, and other oral health conditions, and are frequently studied in oral microbiology [28,34,48].
As extensively documented in the literature on plant essential oils and extracts, Grampositive bacteria have shown lower resistance when exposed to essential oils from native Brazilian Eugenia species compared with Gram-negative bacteria [22,30,39,56].For example, in the study by Toledo et al. [30], essential oil from E. involucrata leaves showed activity against the Gram-positive bacteria S. aureus, S. epidermidis, and B. subtilis (MIC = 875 µg/mL).In contrast, no antimicrobial effect of the essential oil against Gram-negative bacteria (e.g., E. coli, S. Enteritidis, and S. Typhimurium) was recorded.Moreover, the MIC of the essential oil from E. uniflora leaves against S. aureus was reported to be at least four times lower than the value recorded for E. coli (Table 3) [39].
Differences in the effects on Gram-negative and Gram-positive bacteria following exposure to the essential oils are related to the presence of an outer phospholipid membrane enveloping the Gram-negative bacteria cell wall [66].This membrane incorporates hydrophilic lipopolysaccharides, which act as a barrier against macromolecules and hydrophobic compounds, enhancing tolerance to certain antimicrobial agents, such as compounds of essential oils [48,66].Although Gram-positive bacteria possess a cell wall thicker than Gram-negative bacteria, it is primarily composed of lipophilic ends of lipoteichoic acids, which facilitates the direct interaction of essential oils with the bacterial cell [30].
Interestingly, studies revealed variability in susceptibilities among strains of the same microbial (e.g., S. aureus) and/or the same microbial genus (e.g., Staphylococcus spp.) when exposed to native Brazilian Eugenia species.For example, a methicillin-resistant S. aureus strain was more susceptible to the essential oil from E. pyriformis leaves than a nonresistant S. aureus strain, with MIC values equal to 125 and 250 µg/mL, respectively [56].Additionally, S. Typhimurium was more sensitive to the essential oil from E. uniflora leaves than S. Gallinarum, with MIC values equal to 0.78 and 3.13 mg/mL, respectively [38].Bacillus licheniformis was also more susceptible to the essential oil from E. uniflora leaves compared with B. subtillis, with MIC values equal to 0.625 and 5 mg/mL, respectively [44].
Variability in susceptibilities among strains of the same microbial species or genus when exposed to native Brazilian Eugenia species can be attributed to several factors.Firstly, microbial strains exhibit genetic variability, leading to differences in membrane permeability, cell wall composition, and the expression of resistance genes, which consequently affect their response to essential oils.Moreover, resistant strains may possess specific resistance mechanisms, including efflux pumps or enzymatic degradation pathways, while susceptible strains may lack or have reduced expression of these mechanisms.Differences in cellular physiology, growth characteristics, and metabolic activity among strains can also impact their susceptibility to essential oils [63].
As discussed in Section 3, different factors can affect the chemical composition of essential oils, which, in turn, can reflect on their antimicrobial activities.For example, in the study by Siebert et al. [31], the essential oil from E. brasiliensis leaves extracted in the autumn and winter was more active against S. saprophyticus and P. aeruginosa than essential oils obtained in the spring and summer (Table 3).Furthermore, in the study by Sviech et al. [45], no antimicrobial effect was observed for essential oil from E. uniflora leaves against the E. coli strain ATCC 25922 (no inhibition zones by the diffusion method when exposed to 40 µL of a 25% (v/v) essential oil solution), while the same bacterial species was susceptible to the essential oil from E. uniflora leaves in the study by Antonelo et al. [38] (MIC = 0.78 mg/mL) (Table 3).In the first study, the compounds germacrome, spathulenol, and curzerene were present in the essential oil at minor concentrations (13.57, 7.49, and 5.31%, respectively), whereas in the latter, essential oil showed major cyclic oxygenated compounds, including curzerene (10.15%), as well as phenolic compounds, like acetosyringone (12.08%), which could partially explain the differences in antimicrobial effects [38,45].
Because of their confirmed antibacterial potential, essential oils obtained from native Brazilian Eugenia species can be used in combination with other microbial inactivation methods, such as antibiotics and non-thermal technologies (e.g., high-pressure processing and pulsed electric fields for food decontamination).In the study by Pereira et al. [39], essential oil from E. uniflora leaves was combined with antibiotics (i.e., amikacin and gentamicin) to inactivate S. aureus and E. coli.Overall, the authors observed a reduction in the antibiotic concentrations required to achieve desired levels of microbial inactivation, evidencing a synergistic effect.However, complex interactions among different substances may be elucidated to optimize the efficacy of these essential oils as antibacterial agents.
C. albicans has shown different susceptibilities to essential oils obtained from native Brazilian Eugenia species.The MIC values of the essential oils from leaves of E. dysenterica, E. involucrata, and E. uniflora against C. albicans strain ATCC 10231 were higher than 10 mg/mL [27], equal to 1.75 mg/mL [30], and equal to 0.39 mg/mL [38], respectively.These results are associated with the diversity of chemical compounds found in essential oils of different plant species.Furthermore, C. parapsilosis was shown to be more sensitive to essential oil from E. uniflora leaves than C. albicans [44], whereas the latter was more sensitive than C. tropicalis and C. krusei when subjected to the same plant essential oil [40,62].Besides differences in the chemical compositions of essential oils, the biological variability between yeast and fungal species, as discussed for bacterial strains and genera, also plays a relevant role in their sensitivities.
The anti-yeast and antifungal potential of essential oils obtained from native Brazilian Eugenia species is attributed to the presence of some phytochemicals including monoterpenes and sesquiterpenes [34,36,56].Because of its lipophilic nature, the essential oil can permeate the yeast and fungal cell walls, disrupting the activity of enzymes crucial for its synthesis.Furthermore, essential oils can also create a pH gradient across the cytoplasmic membrane, avoiding energy production and inducing changes in yeast and fungal membrane structure [66].
Besides the determination of the MIC and MFC, researchers have applied the agar diffusion method to evaluate the effects of essential oils from leaves of E. brasiliensis and E. uniflora on the growth of F. oxysporum (Table 3).A significant level of inhibition was observed for both essential oils 72 h after their application (66.5% inhibition).Germacrone, which accounted for approximately one-third of the composition of the essential oil from E. uniflora leaves (34.59%), is considered a potent antimicrobial compound, while the presence of oxygenated terpenoids, phenolic alcohols, and aldehydes present in the essential oil from E. brasiliensis leaves are relevant for its fungicidal activity [33].
Overall, the results of antimicrobial screening tests of essential oils obtained from native Brazilian Eugenia species reported in previous investigations showed different levels of microbial inactivation, which can be attributed to their highly diverse chemical composition.These results provide information for developing biopreservation solutions for foods and alternative drugs to treat infections caused by the evaluated microorganisms.Future studies should focus on the optimization of strategies for the application of these essential oils in foods.Additionally, the antimicrobial efficacy of their application in combination with currently applied antibiotics or methods for microbial inactivation must also be considered and evaluated.

Antioxidant Activity
Oxidative stress or cellular damage triggered by free radicals or reactive oxygen/nitrogen species (ROS/RNS) appears to be the fundamental mechanism behind the development of various non-communicable diseases (NCDs), including inflammatory, cardiovascular, neurodegenerative, and other chronic diseases.Compounds naturally present in foods or medicinal plants can scavenge free radicals and ROS/RNS, acting as antioxidants and consequently reducing oxidative damage [67].Several in vitro studies have demonstrated that essential oils obtained from native Brazilian Eugenia species exhibit antioxidant activity in different assays (see Table 4).ABTS: 2,2 ′ -azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging activity, DPPH: 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity, EO: essential oil, FRAP: ferric-reducing antioxidant power, and IC 50 : essential oil concentration that resulted in a 50% reduction in radical concentration compared to the untreated control.
Among native Brazilian Eugenia species, essential oils from E. uniflora were the most investigated for their antioxidant activity.Furthermore, most studies evaluated the antioxidant activity of the plant leaves (Table 4), while only one study assessed the essential oil of other plant parts, namely, the flowers [34].Regarding the commonly used in vitro methods for screening the antioxidant activity of Eugenia species essential oils, the DPPH assay has been the most applied.At the same time, some studies have also conducted ABTS, FRAP, β-carotene/linoleic acid, iron-reducing power, and phosphomolybdenum-reducing assays.Additionally, most studies chose to determine the antioxidant activity of essential oils through the IC 50 , which refers to the concentration of essential oil that results in the inhibition and/or sequestration of 50% of a radical species compared with the control [45].
Plant essential oils consist of a complex mixture of compounds that can exhibit different antioxidant mechanisms of action.Therefore, for a better understanding of the antioxidant potential of an essential oil, it is necessary to subject it to various antioxidant assays that evaluate different mechanisms of action, including assays based on hydrogen atom transfer (e.g., β-carotene/linoleic acid) and single electron transfer (e.g., FRAP, phosphomolybdenum-reducing, and iron-reducing power), as well as mixed-mode assays (e.g., DPPH and ABTS) [69].Considering the different mechanisms of action evaluated by the various antioxidant assays, all essential oils from native Brazilian Eugenia species exhibited some antioxidant activity.For example, the essential oil from E. stipitata leaves was most active in the β-carotene bleaching assay, indicating that its compounds act particularly through hydrogen atom transfer [21].On the other hand, essential oils from E. brasiliensis and E. uniflora leaves seemed to be more effective as single electron donors (they showed high antioxidant activity values in the FRAP, iron-reducing power, and phosphomolybdenum-reducing assays) and almost ineffective as hydrogen atom donors (they showed low antioxidant activity values in the β-carotene/linoleic acid assay) [31,38,45,46].The essential oil from E. stipitata leaves showed similar antioxidant activity values in the DPPH and ABTS assays, as both assays are mixed-mode tests [21,22].The different profiles and contents of compounds present in the essential oils are responsible for the variation in antioxidant activity values and observed mechanisms of action among the essential oils of native Brazilian Eugenia species.Carneiro et al. [34] evaluated the effect of plant part and drying method on the antioxidant activity of E. klotzschiana essential oils and observed that both factors substantially impact the antioxidant activity values observed in the DPPH and ABTS assays.The authors reported that the essential oil obtained from the flowers (IC 50 value of 5.70 µg/mL for DPPH and 104.61 µM Trolox equivalents/g for ABTS) exhibits higher antioxidant activity than the essential oil from the leaves (IC 50 value of 29.77 µg/mL for DPPH and 57.81 µM Trolox equivalents/g for ABTS).Additionally, they found that the essential oil obtained from shade-dried leaves (IC 50 value of 6.48 µg/mL for DPPH and 143.85 µM Trolox equivalents/g for ABTS) was more active than that obtained from leaves dried by forced air circulation at 40 • C (IC 50 value of 7.61 µg/mL for DPPH and 106.27 µM Trolox equivalents/g for ABTS).Both the plant part and the drying method affected the profile and content of active principles in E. klotzschiana essential oils, explaining the different antioxidant activity values found (for more details on the chemical composition, see Table 2).
Seasonality is another important factor that can affect an essential oil's chemical composition and its antioxidant activity.Some studies have demonstrated the effect of seasons on the composition and antioxidant activity of essential oils from E. brasiliensis and E. uniflora leaves [31,47,50].When evaluating the impact of seasonality on essential oil from E. brasiliensis leaves, Siebert et al. [31] found that the highest inhibition of lipid peroxidation was observed for the essential oil from the spring (14.05% inhibition).At the same time, the best iron-reducing power was recorded for the essential oil from the autumn (94.32 mg ascorbic acid equivalents/g).Essential oil from the spring was mainly composed of spathulenol (16.02%), τ-cadinol (15.30%), 1-epi-cubenol (7.02%), and α-cadinol (6.04%), while τ-cadinol (12.83%), β-caryophyllene (8.65%), spathulenol (8.10%), and globulol (7.87%) were the predominant compounds in the essential oil from the autumn.The different profiles and contents of active compounds observed among essential oils obtained in different seasons may explain their different antioxidant activity values and mechanisms of action.
On the other hand, Cipriano et al. [50] observed that the essential oil from E. uniflora leaves obtained in the summer showed the highest antioxidant activity value in the DPPH assay (IC 50 value of 0.62 mg/mL), followed by the oils from the spring, winter, and autumn (IC 50 values of 0.98, 2.01, and 2.73 mg/mL, respectively).The authors attributed the highest antioxidant activity values of the essential oils from the summer and spring to the higher concentration of germacrone present in them (45.00 and 48.05%, respectively) compared with essential oils from other seasons (41.15-42.68%),as germacrone has been reported as a potent free radical scavenger.Similar results were reported by da Costa et al. [47] in essential oils from E. uniflora leaves, where the most active essential oils were those obtained from leaves collected in December and January (435.0 and 436.3 mg Trolox equivalents/g, respectively), which corresponds to the Brazilian summer.The authors verified through hierarchical clustering analysis (HCA) and principal components analysis (PCA) that these essential oils exhibited great similarity in their chemical compositions.
Some studies have also shown that the specimen and genotype can also affect the antioxidant activity of essential oils from Eugenia species [46,52].Figueiredo et al. [46] evaluated the antioxidant activity of the essential oil from the leaves obtained from five different E. uniflora specimens.They found that the highest antioxidant activities were reported for specimens 3 and 4 (228.3 and 217.0 mg Trolox equivalents/mL, respectively), which belonged to chemotypes II and III, respectively.Chemotype II displayed significant content of selina-1,3,7(11)-trien-8-one (18.1%) and selina-1,3,7(11)-trien-8-one epoxide (16.0%), followed by a highlighted amount of caryophyllene oxide (18.1%).Meanwhile, chemotype III was dominated by curzerene (50.6%), followed by germacrene B (5.2%) and germacrone (4.5%).Cipriano et al. [52] studied the antioxidant activity of essential oils obtained from the leaves of 36 E. uniflora genotypes.The authors noted that genotype significantly impacts the antioxidant activity of the essential oils, with values ranging between 176.66 and 867.57µmol Trolox equivalents/L.Genotypes A05, A11, and A29 exhibited the most active essential oils (867.57,861.51, and 843.33 µmol Trolox equivalents/L).The essential oils from genotypes A05 and A11 were dominated by germacrone (46.52 and 65.03%, respectively), followed by curzerene (7.95 and 9.21%, respectively).On the other hand, the essential oil from genotype A29 was particularly composed of curzerene (18.45%), followed by similar amounts of germacrene B (9.40%), germacrone (9.15%), and furanodiene (8.36%).These findings demonstrate that different chemical compositions can result in similar antioxidant activities.Thus, the antioxidant activity of essential oils should not be considered solely concerning their major constituents, as the synergistic action of other minor components may contribute to an increase in antioxidant activity.
These outcomes demonstrate that the essential oils from native Brazilian Eugenia species can be promising sources of natural antioxidants for managing diseases related to oxidative stress, such as non-communicable chronic diseases.Additionally, they can also be used in the food industry as substitutes for synthetic antioxidants, extending the shelf life of food products.The pharmaceutical and cosmetic industries can also utilize their antioxidant characteristics to develop innovative products.

Anticancer Activity
Cancer encompasses a range of conditions marked by uncontrolled and excessive cellular proliferation, leading to the formation of abnormal tissue masses.This disease poses a substantial public health challenge worldwide, impacting approximately 11 million individuals annually and contributing to one in every six deaths globally [70].Recent studies have revealed the promising anticancer potential of essential oils from areal parts of native Brazilian Eugenia species against different types of cancer (see Table 5).• EO was active against colon (HCT116), gastric (AGP01), and melanoma (SKMEL-19) human cancer cells with IC 50 = 9.28 to >25 µg/mL, 8.23 to >25 µg/mL, and 12.20 to >25 µg/mL.

•
Curzerene purified from EO increased the number of apoptotic cells, reduced the number of viable cells, and inhibited cell migration in the human melanoma cell model. [ Leaves Three human cancer cell lines including HeLa, MCF7, and M059J • Breast (MCF7), glioblastoma (M059J), and cervical adenocarcinoma (HeLa) human cancer cells with IC 50 = 76.5, 84.5, and 106.2 µg/mL. [48]
As can be seen in Table 5, the anticancer activity of essential oil from E. uniflora leaves has been evidenced by different studies.Antonelo et al. [38] noticed that essential oil from E. uniflora leaves exhibited low cytotoxic activity against human adrenocortical carcinoma (H295R cells, IC 50 value of 322.94 µg/mL), being even more cytotoxic against non-cancerous kidney epithelial cells (VERO cells, IC 50 value of 101.37 µg/mL).On the other hand, Sobeh et al. [44] demonstrated that this essential oil was able to significantly inhibit the proliferation of human breast cancer cells (MCF7 cells, IC 50 value of 76.4 µg/mL).A very similar result was found by da Silva et al. [48] when evaluating the effect of essential oil from E. uniflora leaves on the same cancer cell line (MCF7 cells, IC 50 value of 76.5 µg/mL).Additionally, the authors demonstrated that this essential oil was also effective against glioblastoma (M059J cells) and cervical adenocarcinoma (HeLa cells) human cancer cells, with IC 50 values of 84.5 and 106.2 µg/mL, respectively.However, it was highly toxic to non-cancerous human lung fibroblasts (GM07492A cells, IC 50 value of 39.8 µg/mL), which would limit its use because of low selectivity.In another study, Figueiredo et al. [46] investigated the effect of essential oil obtained from the leaves of different E. uniflora specimens against three human cancer cell lines (colon (HCT116 cells), gastric (AGP01 cells), and melanoma (SKMEL-19 cells)) and non-malignant human lung fibroblast cells (MRC5 cells).Their results demonstrated that the essential oils obtained from E. uniflora specimens 2 and 4, which contained significant amounts of selina-1,3,7(11)-trien-8-one (43.1%), selina-1,3,7(11)-trien-8-one epoxide (21.7%), and curzerene (50.6%), displayed the highest antiproliferative activities against all tested cancer cell lines (IC 50 values ranging from 8.73 to 16.26 µg/mL).However, once again, these essential oils showed a high cytotoxic effect against normal cells (MRC5 cells, IC 50 values of 10.27 and 14.95 µg/mL, respectively).The geographical origin and growth conditions (e.g., fertilization, maturity, soil conditions, climatic conditions, and seasonal factors) of the plant had a significant impact on the chemical composition of its essential oils, directly reflecting the different results of anticancer activity presented by the evaluated E. uniflora specimens [44,46].Figueiredo et al. [46] also evaluated the cytotoxic effect of curzerene, the main compound found in the essential oil from E. uniflora leaves of specimen 4 (50.6%), and found that this compound was highly active against all cancer cell lines (IC 50 values ranging from 5.17 to 9.18 µmol/L), particularly against human melanoma cells (SKMEL-19 cells), with an IC 50 value and a selectivity index of 5.17 µmol/L and 2.21, respectively.Furthermore, further analysis revealed that curzerene exerted its anticancer effect on melanoma cells by inducing cellular apoptosis and inhibiting cell migration [46].
In addition to the essential oil of E. uniflora leaves, essential oils from the aerial parts of E. stipitata, E. involucrata, and E. pyriformis also displayed antiproliferative activity (see Table 5).Jerônimo et al. [23] investigated the cytotoxic effect of the essential oil from E. stipitata leaves against four human cancer cell lines (breast (MCF7 cells), melanoma (SKMEL-19 cells), gastric (AGP01 cells), and colon (HCT116 cells)) and non-malignant human lung fibroblast cells (MRC5 cells).The essential oil was active against melanoma and breast human cancer cells (IC 50 values of 17.2 and 19.1 µg/mL, respectively), but it also exerted a toxic effect on normal human fibroblasts (IC 50 value of 13.8 µg/mL), demonstrating effectiveness but low selectivity against cancer cells.Similar results were reported by D'Almeida et al. [29] for the essential oil from E. involucrata leaves, in which the authors also found a highly cytotoxic effect against murine melanoma cells (B16F10 cells) and human breast cancer cells (MCF7 cells), as well as non-cancerous murine fibroblasts (McCoy cells) (IC 50 values of 14.12, 24.06, and 16.59 µg/mL, respectively).Morphological analyses demonstrated that this essential oil promoted cell death through the induction of apoptosis, as morphological changes consistent with apoptosis rather than necrosis were observed in the cells, including blebs formation, chromatin condensation, and cell rounding.Similarly, Durazzini et al. [57] studied the antiproliferative effect of the essential oil from the aerial parts of E. pyriformis (leaves and twigs) against three human cancer cell lines (breast (MCF7), glioblastoma (M059J), and cervical adenocarcinoma (HeLa)) and human lung fibroblasts (GM07492A cells).The essential oil was most active against human breast cancer cells (MCF7 cells, IC 50 value of 73.09 µg/mL), showing effects similar to the positive control doxorubicin (IC 50 value of 62.10 µg/mL) and high selectivity (selectivity index of 1.91).
In short, the promising cytotoxic and antiproliferative effects against different types of cancer cells exhibited by essential oils from Brazilian native Eugenia species can be explained by the presence of various bioactive phytochemicals in their compositions, primarily terpene compounds (for more details regarding the composition of these essential oils, please refer to Table 2).The literature has reported that some terpenes identified in these essential oils (e.g., β-caryophyllene, β-elemene, curzerene, germacrene D, and bicyclogermacrene) have significant anticancer activity [71][72][73][74].These compounds generally act synergistically, with their primary target in the cell being the cytoplasmic membrane.Studies have reported that these substances can disrupt cell membranes and impact crucial cellular functions, leading to cell death by apoptosis or necrosis [57].However, the few molecular studies conducted with essential oils from Brazilian native Eugenia species have indicated that they predominantly act through cellular apoptosis [29,46].
Unlike the essential oil from E. stipitata leaves, the essential oils from E. dysenterica and E. uniflora leaves and E. klotzschiana flowers exhibited high trypanocidal activity (see Table 6).The essential oil from E. dysenterica leaves was highly active against T. cruzi trypomastigotes (LC 50 value of 9.5 µg/mL), with an effect practically equal to that exerted by the reference drug benznidazole (LC 50 value of 9.8 µg/mL) [28].Similar results were observed by Carneiro et al. [35] for the essential oil from E. klotzschiana flowers against T. cruzi trypomastigotes (LC 50 value of 20.2 µg/mL).Although less active than the reference drug benznidazole, this essential oil exhibited low cytotoxicity against fibroblast cells (LC 50 value of 220.3 µg/mL), demonstrating its highly selective action against the protozoa (selectivity index of 10.91).Sobeh et al. [44] also found a high susceptibility of T. brucei brucei to the essential oil from E. uniflora leaves with a selectivity index of 6.82.
In addition to the essential oil from E. stipitata leaves, the essential oils from the aerial parts of E. uniflora and E. pyriformis also exhibited promising leishmanicidal effects (see Table 6).The essential oils from E. uniflora leaves [48], E. pyriformis leaves [77], and the aerial parts of E. pyriformis (leaves and twigs) [57] were highly active against L. amazonensis promastigotes, with LC 50 values of 0.99, 19.73, and 2.16 µg/mL, respectively.da Silva et al. [48] found that the essential oil from E. uniflora leaves (LC 50 value of 0.99 µg/mL) exhibited a leishmanicidal effect very close to that of the standard drug amphotericin B (LC 50 value of 0.60 µg/mL).Likewise, Kauffmann et al. [77] observed that the essential oil from E. pyriformis leaves and the standard drug pentamidine isethionate showed almost equal effectiveness against L. amazonensis (LC 50 values of 19.73 and 23.22 µg/mL, respectively).Meanwhile, Durazzini et al. [57] demonstrated that the essential oil from the aerial parts of E. pyriformis (leaves and twigs) had only moderate cytotoxicity against human lung fibroblasts (LC 50 value of 141.27 µg/mL), being highly selective against L. amazonensis (selectivity index of 65.4).
The promising antiparasitic activity against Trypanosoma spp.and Leishmania spp.exhibited by the essential oils of native Brazilian Eugenia species may be due to the major constituents identified in each essential oil, particularly terpenes (for more details regarding the composition of these essential oils, please refer to Table 2).Different terpenes identified in these essential oils possess recognized trypanocidal and leishmanicidal activities reported in the literature (e.g., α-pinene, β-eudesmol, γ-eudesmol, caryophyllene oxide, limonene, citral, β-caryophyllene, eugenol, and nerolidol) [78][79][80][81][82][83][84][85][86][87][88].These compounds can act synergistically, enhancing the antiparasitic effect of each essential oil.Because of their hydrophobic nature, the terpenes present in the essential oils can diffuse through a parasite's cell membrane, thus affecting its metabolic pathways and intracellular organelles [35].These substances can interact with polysaccharides, lipids, and phospholipid layers in parasite membranes, inducing cellular lysis and macromolecule extravasation.Once in the cytoplasm, these compounds can interrupt specific metabolic pathways of proteins and lipids or stimulate the depolymerization of the mitochondrial membrane by decreasing membrane potential, affecting ionic Ca 2+ cycling and other ionic channels, and reducing the pH gradient that disturbs the proton pump and ATP pool.This depolymerization affects the fluidity of the inner and outer mitochondrial membranes, which become abnormally permeable, resulting in the release of radicals, calcium ions, cytochrome C, and proteins that, in turn, lead to the parasite's death by necrosis and apoptosis [22,48].
These studies demonstrate that the essential oils from native Brazilian Eugenia species can be promising and innovative sources of active agents for developing drugs to treat NTDs, particularly trypanosomiasis and leishmaniasis.

Other Biological Activities
In addition to the biological activities already mentioned and addressed above, essential oils from some native Brazilian Eugenia species exhibit anti-inflammatory, antinociceptive, antipyretic, antidiarrheal, and wound healing effects, as listed in Table 7. Endogenous or exogenous antigens can interact with the cellular immune system, leading to the generation of ROS and RNS, which, in turn, trigger signaling cascades that may result in the hyperactivation of inflammatory responses.These responses can induce oxidative stress and tissue damage phenomena, which are the main factors contributing to the development, progression, and worsening of most known diseases [89].Studies conducted in in vitro, cellular, and animal models have demonstrated that essential oils from E. stipitata, E. dysenterica, and E. uniflora leaves exhibit promising anti-inflammatory activities (see Table 7).
Costa et al. [24] evaluated the anti-inflammatory effect of the essential oil from E. stipitata leaves in in vitro (inhibition of protein denaturation) and animal models (mice orally treated with the essential oil).Their study demonstrated that the essential oil from E. stipitata leaves was able to inhibit BSA denaturation, exhibiting greater inhibitory effects (74.38-77.20%inhibition) compared with the standard drug sodium diclofenac (45.02-67.00%inhibition) when evaluated at the same concentrations (0.25 to 1 mg/mL).The anti-inflammatory effects of this essential oil were confirmed in animal models (carrageenan-induced acute inflammation), where its oral administration (40-250 mg/kg bw) reduced paw edema volume (88.66-96.94%inhibition) and the migration of leukocytes (76.9-86.5% inhibition) and neutrophils (74.5-77.9%inhibition) into the peritoneal cavity of mice.It is important to note that these results were similar or even superior to those found for the standard drug indomethacin at 20 mg/kg bw.Furthermore, no death or alteration in behavior signs, water and food consumption, and biochemical, hematological, or histopathological parameters were observed in mice treated with 2000 mg/kg bw during the 14 experiment days, demonstrating that this essential oil is non-toxic.The authors attributed the anti-inflammatory effects particularly to β-caryophyllene, one of the major compounds in this essential oil (11.36% of the oil composition), which is capable of reducing the synthesis/expression of inflammatory mediators such as prostaglandin E2, IL-1β, and TNF-α.
da Silva et al. [26] found that the essential oil from E. dysenterica leaves and α-humulene (one of the main components of the essential oil, accounting for approximately 19.3% of its composition) also exhibited anti-inflammatory activity by inhibiting nitric oxide production in LPS-stimulated RAW 264.7 murine macrophages.Moreover, both the essential oil (146.3 and 292.6 µg/mL) and α-humulene (155.58 and 311.15 µg/mL) were significantly more active than the positive control dexamethasone (62.5 and 125 µg/mL) and showed low cytotoxicity against mouse fibroblast cells (L929) and macrophages cells (RAW 264.7) (LC 50 ≤ 292 µg/mL).This essential oil is predominantly composed of α-humulene (19.3%) and β-caryophyllene (24.36%).The authors suggested that these compounds may be involved in the anti-inflammatory responses of the essential oil since the literature shows that they inhibit various pro-inflammatory mediators, including interleukins (IL-2, IL-10, and IL-1β), TNF-α, histamine, and prostaglandin E2.
Anti-inflammatory effects have also been reported for the essential oil from E. uniflora leaves.de Jesus et al. [43] found that oral treatment of mice with essential oil from E. uniflora leaves reduced xylene-induced ear edema at all tested doses (50-200 mg/kg bw; 50.26-55.17%inhibition) and carrageenan-induced leukocyte recruitment in the peritoneal cavity at a concentration of 200 mg/kg bw (47.25% inhibition).It is noteworthy that treatment with 200 mg/kg bw showed leukocyte migration inhibition results significantly equal to the control drug dexamethasone at 1 mg/kg bw.Additionally, oral administration of up to 2000 mg/kg bw did not induce behavioral changes, mortality, or impairments in hepatic and renal functions of the mice over 14 experiment days, demonstrating the absence of acute oral toxicity.The authors attributed the anti-inflammatory effects of this essential oil to its ability to inhibit the release of inflammatory mediators, reducing vascular permeability and vasodilation, and, consequently, leukocyte and neutrophil migration.Curzerene (33.4%), caryophyllene oxide (7.6%), β-elemene (6.5%), and β-caryophyllene (4.1%) were the major components identified in this essential oil.These compounds may be associated, at least in part, with the anti-inflammatory effects exerted by the essential oil from E. uniflora leaves.
It is well documented in the literature that plants exhibiting anti-inflammatory activity also exert analgesic and antipyretic effects.In fact, the essential oils from E. stipitata and E. uniflora leaves, which were potent anti-inflammatory agents, also demonstrated antinociceptive and/or antipyretic activity in animal models (see Table 7).Different doses of essential oil from E. stipitata leaves (40-250 mg/kg bw) were able to reduce rectal temperature from the first hour after the oral administration in mice induced by Saccharomyces cerevisiae.The animals' temperatures remained below febrile values from 1 h and were maintained until the end of the experiment (4 h).Additionally, this essential oil exhibited analgesic effects by reducing the number of acetic acid-induced abdominal writhings in mice (54.1-56.6%inhibition) [24].Similar results were reported by de Jesus et al. [43] in mice treated with essential oil from E. uniflora leaves.They noted that oral administration of this essential oil reduced the number of acetic acid-induced abdominal writhings (50-200 mg/kg bw; 33.33-61.66%inhibition), formalin-induced neurogenic (200 mg/kg bw; 63.43% inhibition), and inflammatory pain (50-200 mg/kg bw; 30.54-80.87%inhibition) but did not increase latency to response in the hot-plate test.Furthermore, no changes in motricity or sedation were observed in animals treated with essential oil from E. uniflora leaves (300 mg/kg bw), demonstrating that the analgesic results were not influenced by motor or sedative effects.These results demonstrate that these essential oils have peripheral antinociceptive action but not central.The antipyretic and analgesic effects observed in these essential oils may be associated with their major components (e.g., β-caryophyllene) that can reduce the expression of inflammatory mediators, as discussed above, and act as an endocannabinoids type 2 agonist [24,43].
In addition to anti-inflammatory activity, antidiarrheic and wound healing effects have also been reported in essential oils from E. dysenterica leaves (see Table 7).Galheigo et al. [25] noticed that oral administration of essential oil from E. dysenterica leaves (300 mg/kg bw) reduced castor oil-induced diarrhea by decreasing the total number of feces, the number of diarrheic feces, and the accumulation of intestinal fluids without altering the distance traveled by charcoal meal in the intestine.These results suggest that the antidiarrheic effect of this essential oil and its volatile components (particularly (Z)-β-ocimene (19.14%) and βcaryophyllene (15.36%)) seems to be linked to its ability to inhibit intestinal secretion and/or increase intestinal absorption without involving the inhibition of gastrointestinal motility.In another study, da Silva et al. [26] demonstrated that essential oil from E. dysenterica leaves (542.2 µg/mL) stimulated the migration of skin cells (fibroblasts) in mechanically induced wounds, promoting complete wound closure in just 12 h.This essential oil proved to be safe for dermatological applications as it did not cause irritation or injury to the skin in the chorioallantoic membrane assay at concentrations ≤ 292 µg/mL.Additionally, the essential oil exhibited anti-inflammatory activity by inhibiting nitric oxide production in LPS-induced macrophages and angiogenic effects by increasing the number of blood vessels in the chorioallantoic membrane assay.Thus, essential oil from E. dysenterica leaves may promote wound healing by modulating inflammation, cell migration, and blood vessel sprouting.Instrumental analyses have shown that this essential oil contains high concentrations of bioactive sesquiterpene compounds, such as β-caryophyllene (24.36%) and α-humulene (19.3%), suggesting that these compounds may act synergistically and be responsible for their wound healing activity.
These studies together demonstrate that the essential oils of Brazilian native Eugenia species can be promising sources of active principles for the development of drugs and cosmetics aimed at wound healing, pain relief, fever, diarrhea, and inflammatory processes.

Limitations, Challenges, and Future Research Directions
Although the findings compiled here have demonstrated that essential oils obtained from native Brazilian Eugenia species can inhibit or delay food spoilage microbial growth and oxidative processes, there are still significant limitations to the current findings, particularly related to their effectiveness in food systems.Moreover, more advanced analytical techniques are needed to better explore the antioxidant and antimicrobial mechanisms of these essential oils, as the specific in vitro assays that produce positive results are conducted under simple and highly controlled laboratory conditions that do not mimic the environment found in food systems, making it difficult to scale up these procedures to a commercial level.Therefore, it is essential to develop and standardize formulations with these essential oils to reduce chemical variability and consequently improve their efficacy as natural preservative agents.Additionally, the effectiveness of these essential oils needs to be evaluated in complex food systems (e.g., food packaging, edible films, food products, among others) to confirm the findings observed in controlled systems.Toxicological studies must also be conducted to ensure that the effective concentrations of these essential oils in food systems do not compromise the health and well-being of consumers.
These essential oils can be sources of active principles for the development of cosmetics, personal hygiene products, and medications to treat/manage various pathological conditions, such as foodborne intoxications and infections caused by pathogenic microorganisms, oxidative stress, cancer, inflammation, pain, fever, diarrhea, wounds, and diseases associated with human parasites, including Chagas disease and leishmaniasis.However, most of these studies have been conducted in vitro under conditions that do not always replicate the complex biological environments found in vivo.Furthermore, the chemical complexity of these essential oils complicates the standardization of treatments and the precise prediction of therapeutic outcomes.Translating the results reported in in vitro and animal studies into clinical applications faces several obstacles, including toxicity, volatility, and instability.Thus, it is essential to conduct clinical studies to validate health claims and determine the toxic dose of these essential oils to ensure that the developed products are safe and effective for consumers.Furthermore, cutting-edge technologies for encapsulating these essential oils (e.g., nanoencapsulation, liposomes, and emulsions) can be applied to increase stability and reduce the volatility of the active principles and control and direct their release in a target tissue, thereby improving their efficacy and safety.The synergy between these essential oils and other conventional drugs can also be another research area to explore, as their combination may reduce the effective doses required for managing pathologies and minimize the side effects of conventional medications.

Conclusions
Brazilian native plants have attracted growing interest from consumers and researchers around the world because of their unique flavor and aroma characteristics as well as claims of beneficial health effects.Among these, plants belonging to the genus Eugenia stand out because of the large number of species spread across Brazilian territory.The data collected here demonstrate that some native Brazilian Eugenia species have emerged as potential sources for obtaining essential oils with significant biological properties, such as E. stipitata, E. dysenterica, E. involucrata, E. brasiliensis, E. klotzschiana, E. uniflora, and E. pyriformis.Instrumental analyses have shown that the essential oils obtained from these plants are composed of extremely complex mixtures of phytochemicals, potentially containing more than 80 compounds.Sesquiterpene hydrocarbons and their oxygenated derivatives are the main components of these essential oils, with monoterpenes and other classes of compounds (e.g., phenylpropanoids) being found only in small quantities.The synergism among these different classes of compounds may explain the biological activities of these essential oils observed in in vitro assays and animal trials, as essential oils with different compositions presented similar effects.Evidence has shown that several factors can affect the chemical composition of these essential oils and consequently their biological activities, including plant part, sample preparation, extraction conditions, soil composition and climatic conditions where the plant grows, season, age and vegetative cycle stage, and genotypes or specimens, among others.
The discoveries made so far demonstrate that the native Brazilian Eugenia species can be a valuable source of essential oils with active principles for developing innovative and sustainable products for food, medicinal, and cosmetic applications.Thus, these essential oils can be used as a strategic action to meet some SDGs, particularly SDG 3 (good health and well-being), SDG 9 (industry, innovation, and infrastructure), and SDG 12 (responsible consumption and production).However, some gaps, particularly those related to the effectiveness of these essential oils as preservative agents in food systems and the confirmation of their safety and beneficial effects through clinical/toxicological studies, still need to be further explored in future studies.Furthermore, it is important to emphasize that sustainable practices must be adopted throughout the production chain to ensure the preservation of Brazilian biodiversity.

Table 2 .
Major compounds found in essential oils from native Brazilian plants of the genus Eugenia.

Table 3 .
A summary of studies showing the in vitro antimicrobial activities of essential oils obtained from native Brazilian plants of the genus Eugenia.
(Staphylococcus aureus and Staphylococcus saprophyticus), two Gram-negative bacterial strains (Escherichia coli and Pseudomonas aeruginosa), and two mollicutes strains (Mycoplasma mycoides subsp.capriandUreaplasma urealyticum)•S.saprophyticus was the most sensitive (MIC = 500 mg/mL in the autumn and winter and 1000 mg/mL in the summer and spring).• P. aeruginosa (MIC = 500 and 1000 mg/mL in the autumn and winter).• E. coli, S. aureus, and the two mollicutes strains (MIC ≥ 1000 mg/mL).• P. nigrescens and S. mutans were the most sensitive; MIC = 50 µg/mL.• S. aureus was more sensitive to the EOs from the autumn and winter (MIC = 1000 µg/mL).

Table 4 .
A summary of studies showing the in vitro antioxidant activity of essential oils obtained from native Brazilian plants of the genus Eugenia.

Table 5 .
A summary of studies showing the in vitro anticancer activity of essential oils obtained from native Brazilian plants of the genus Eugenia.

Table 7 .
A summary of studies showing the other biological activities of essential oils obtained from leaves of native Brazilian plants of the genus Eugenia.