The Presence of Flavonoids in Some Products and Fruits of the Genus Eugenia: An Integrative Review

<jats:p>The Myrtaceae family, one of the most prominent botanical families, is represented in Brazil with different fruit species, rich in bioactive compounds and gastronomically appreciated. This study aimed to carry out an integrative review on the genus <jats:italic>Eugenia</jats:italic>, highlighting the pitangueira (<jats:italic>E. uniflora</jats:italic> L.), cagaiteira (<jats:italic>E. dysenterica</jats:italic>), grumixameira (<jats:italic>E. brasiliensis</jats:italic>), pereira (<jats:italic>E. klotzschiana</jats:italic> O. Berg), and uvaieira (<jats:italic>E. pyriformis</jats:italic> Cambess) and which flavonoids are present in these fruits. Articles published between 2016 and 2021 were selected from the following databases: Google Scholar, Periódicos CAPES, Scielo, and Science Direct. According to each database, the descriptors used as a search strategy addressed the popular and scientific names of the five selected species, associated or not with the term “flavonoid,” according to each database. The results showed that quercetin was the main flavonoid identified in the fruits, and the principal extraction method used was HPLC. Other interesting compounds, such as catechin, epicatechin, rutin, myricetin, and kaempferol, were also found. However, the amount and type of flavonoids detected varied according to the applied methodology. Hence, these studies highlight the importance of species of the genus <jats:italic>Eugenia</jats:italic>, which promotes beneficial health effects and possible applicability to the food and pharmaceutical industry.</jats:p>

section_content: Brazil is recognized worldwide for its sizeable territorial extension and its rich biodiversity of plants filling its distinct and harmonious biomes, which sometimes diverge, sometimes converge in various forms. Among the rich diversity of Brazilian flora, the Myrtaceae family, one of the most prominent botanical families, is characterized by 132 genera and 5,671 species in Brazil (Lucena et al., 2014), and have speciesrich in bioactive compounds and gastronomically appreciated (Veloso, 2015). Among the species of the Myrtaceae family, the genus Eugenia, which represents a third of its species, is widely distributed across the country with their diversity and frequency of occurrence (Romagnolo and Souza, 2006). 

The Brazilian species of Myrtaceae comprise several arboreal and shrub plants that, due to the quality of their fruits, can be used to produce fruits for fresh consumption or industrial process, in the production of pharmaceuticals, and in urban afforestation (Delgado and Barbedo, 2007). They occur mainly in tropical and subtropical regions of the world, often being one of the dominant families in the Brazilian Atlantic Forest (Stefanello et al., 2011). 

The genus Eugenia, with more than a hundred species, comprises some natives of Brazil e with great economic importance, such as E. brasiliensis (grumixameira), E. pyriformis C. (uvaieira), E. uniflora L. (pitangueira), E. dysenterica (cagaiteira), E. klotzchiana O. Berg (cerrado's pereira). These species produce fleshy, yellow, and red fruits (Lamarca et al., 2011). A characteristic of this genus is the low number of seeds in its fruits, which makes it challenging to plant large areas to produce on a commercial scale (Scalon et al., 2012; Filho, 2021). 

Many species of Eugenia are also rich in essential oils and tannins and are frequently used in folk medicine (Lunardi et al., Eugenia brasiliensis (Figure 3 ), commonly known as grumixameira, comes from trees that grow in Brazilian rainforests. The grumixama is a cherry-like fruit, approximately 2. 0 cm in diameter, containing one or several seeds, and is slightly sweet. The purple variety is the most common and is known as the Brazilian cherry (Flores et al., 2012). This plant has economic potential due to its composition's attractive sensory attributes and phenolic compounds, including ellagitannins and flavonoids (Abe et al., 2012). In general, the fruits of this family are known to be good sources of bioactive compounds (Fracassetti et al., 2013). The purple grumixama fruit was rich in anthocyanins, mainly cyanidin-3-glycoside, and carotenoids, mainly monohydroxy carotenoids, such as alltrans-β-cryptoxanthin (Silva et al., 2014). 

Eugenia klotzschiana Berg is a tree native to the Cerrado, known as the pereira do Cerrado, which is very little explored (Xavier Mariano et al., 2020). Characterized by a bushy tree, measuring 1-2 m in height, the ripe fruits vary in size from six to 10 cm in length by four to 7 cm in diameter. The fruits have velvety characteristics, thin peel of yellow color when ripe and soft pulp with a certain astringency and acid flavor (Carneiro, 2015). 

Regarding the consumption of E. klotzschiana fruits (Figure 4 ) in natura, knowing their maturation stages is essential to establish their shelf-life and post-harvest quality (Carneiro, 2015; Sanches et al., 2021). It has significant nutritional value, including the content of polyphenolic compounds and flavonoids, in addition to a considerable content of ascorbic acid and dietary fiber (Mariano et al., 2022). 

Eugenia pyriformis Cambess species (Figure 5 ) is well known for its edible fruits, popularly known as "uvaieira. " At botanical community is classified as a medium-sized arboreal species between 5 and 15 m in height, with a rounded and elongated crown. Have solitary white flowers and golden-yellow fruits, being slightly aromatic, fleshy, and hairy, with a sweet and slightly acidic flavor in the various stages of maturation (Silva et al., 2015; Filho, 2021). The seeds corresponding to approximately 16% of the total fruit weight (Rodrigues D. B. et al., 2021). Several phenolic compounds were isolated from uvaia, among which are flavonoids (quercetin, kaempferol, and rutin) and phenolic acids (gallic, chlorogenic, and caffeic acids) (Rodrigues L. M. et al., 2021). 

Many classes have medicinal and antioxidant properties, characteristics associated with the presence of essential oils and polyphenols, such as tannins and flavonoids, especially anthocyanins (Queiroz et al., 2015). The fruits of Eugenia species tend to have vibrant colors ranging from yellow to purple, indicating the presence of compounds such as anthocyanins and other phenolic derivatives (Queiroz et al., 2015; Rosa, 2021). The antioxidant activity of these fruits is related to the presence of phenolic compounds (Rosa, 2021). Among the flavonoids, the presence of quercetin, methoxyquercetin, myricetin, and kaempferol stands out (Queiroz et al., 2015). 

This group provides fruits much appreciated by Brazilians and others still relatively unknown, such as pitanga (Eugenia uniflora L. ), cagaita (Eugenia dysenterica), grumixama (Eugenia brasiliensis), cerrado pear (Eugenia klotzschiana O. Berg), and uvaia (Eugenia pyriformis Cambess) (Romagnolo and Souza, 2006; Lucena et al., 2014; Veloso, 2015; Helt et al., 2018; Pereira et al., 2020; Ramos et al., 2020; Xavier Mariano et al., 2020; Rodrigues D. B. et al., 2021). These fruits can be consumed fresh or in the form of jellies, jams, and liqueurs (Bueno et al., 2017; Silva et al., 2019; Ramos et al., 2020; Rodrigues D. B. et al., 2021). Some of the medicinal properties attributed to Eugenics fruits are biological actions that promote beneficial health effects. These are related to antioxidants that come from vitamins, carotenoids, and phenolic compounds such as flavonoids (Helt et al., 2018; Mendonça and Vieites, 2019; Castelucci et al., 2020; Ramos et al., 2020; Sobral -Souza et al., 2020; Rosa, 2021; Silva M. et al., 2021). The term flavonoid was derived from the Latin "flavus," which means yellow, and they are essential in the color of flowers. Flavonoids are biosynthesized from the phenylpropanoid route, a mixed route, in which part of the flavonoid skeleton is derived from shikimic acid and the other from acetyl-CoA (Pereira et al., 2016) (Figure 6 ). 

Flavonoids make up a large part of phenolic compounds. They are low molecular weight molecules consisting of polyphenols characterized by 15 carbon atoms in their fundamental nucleus. Besides, that presents two aromatic rings joined by a chain of three carbon atoms (C 6 -C 3 -C 6 ), basic nucleus, and its main nuclei of some classes of flavonoids that may or may not form a third ring (Souto, 2017; Castelucci et al., 2020 ) (Figure 7 ). 

In this context, the present study aimed to carry out an integrative review on the genus Eugenia, highlighting the pitangueira (E. uniflora L. ), cagaiteira (E. dysenterica), grumixameira (E. brasiliensis), pereira do cerrado (E. klotzschiana O. Berg), and uvaieira (E. pyriformis Cambess) and which flavonoids are present in these fruits.
section_name: INTRODUCTION

section_content: The present study consists of an integrative review, which sought articles published between 2016 and 2021 in the following Frontiers in Food Science and Technology | www. frontiersin. org databases: Google Scholar, Periódicos CAPES, Scielo, and Science Direct. Researches were carried out related to the five selected fruits of the genus Eugenia, namely cagaiteira (Eugenia dysenterica), grumixameira (Eugenia brasiliensis), pereira do cerrado (Eugenia klotzchiana Berg), pitangueira (Eugenia uniflora) and uvaieira (Eugenia pyriformis). 

For the elaboration of this work, the following steps were applied: formulation of the guiding question, specification of the strategy methods for researching articles, selection of articles, obtaining the articles that constituted the search criteria, interpretation of results, and presentation of the integrative review (Ramos et al., 2022). 

For the first stage, the guiding question was elaborated, defined as: "What are the possible flavonoids present in certain fruits of the Eugenia genus?". The second step is the search for articles. In Table 1, it is possible to verify the search strategies used for each database and the number of studies found. 

The third step consisted of selecting the articles, following the established inclusion and exclusion criteria, where the titles and abstracts of all scientific files, dissertations, and thesis were read. Also, at this stage, the following inclusion criteria were established: Studies published in the databases as mentioned earlier, scientific productions with published full texts, available in Portuguese, English, or Spanish, that address the use of flavonoids in certain fruits of the Eugenia genus and have been published between 2016 and 2021. As exclusion criteria: studies that did not meet the guiding question. 

In the fourth stage, an analysis was carried out through the complete reading of the selected texts (in total) and definition of the studies included in the integrative review, extracting the highlighted information to answer the research objective. Finally, the fifth stage proceeded with the interpretation and discussion of the results, highlighting the works that brought the most significant answers to the proposed guiding question.
section_name: METHODOLOGY

section_content: The guiding question led to a return of 1785 articles in the following databases: Google Scholar, Periódicos CAPES, Scielo, and Science Direct. According to each database, the popular and scientific names of the five selected Eugenia fruits were used as descriptors in the search strategy, associated or not with the term "flavonoid. "

The search strategy used for Google Scholar brought up 1,390 works. In Periódicos CAPES, 150 articles were found, while Science Direct returned 121 works, and in the Scielo platform, 124 studies were found. Of the 222 works retrieved in the third step, 65 duplicates were removed. A total of 157 works were selected for the subsequent stage. After a complete reading of 157 articles, 131 were excluded for not answering the guiding question. The 26 remaining articles went on to the last stage: interpretation and discussion of the results. This selection process is detailed in Figure 8. 

Table 2 summarizes the data relating to the 26 articles that address the flavonoids present in Eugenia fruits. It is observed that most studies dealt with pitanga (E. uniflora) and cagaita (E. dysenterica). Articles from 2020 to 2021 corresponded to 42. 3% of the selected works, and only two of the works that answered the guiding question were from the year 2016. 

Flavonoids represent one of the most important phenolic groups, as they are an extensive class of antioxidants. In plants, they are essential for plant growth and reproduction. They are found in plant species such as fruits, seeds, peel, roots, Frontiers in Food Science and Technology | www. frontiersin. org flowers and contribute to imparting sensory characteristics such as color and astringency (Guedes et al., 2017; Silva et al., 2019; Rodrigues D. B. et al., 2021). Even in small amounts, these compounds have physiological effects through their antioxidant action, playing an essential role in the processes of inhibiting the risk of cardiovascular diseases and several chronicdegenerative diseases, such as diabetes, cancer, and inflammatory processes (Guedes et al., 2017; Migues et al., 2018; Silva P. R. D. et al., 2021). Table 3 shows the main flavonoids described in the literature for Eugenia. 

According to Table 2, it appears that quercetin was the main flavonoid identified in Eugenia fruits, mentioned in 92. 3% (24) of the studies retrieved. Moreira et al. (2017) demonstrated that cagaita leaf extract could be used in cosmetic/pharmaceutical products. This statement is due to the presence of antioxidant phytochemicals, such as quercetin, which is associated with regenerative effects of cells against damage induced by UVA exposure and considerable inhibitory activity of skin enzymes related to dermatological or aesthetic disorders. Other interesting compounds were also found in Eugenia fruits, such as catechin, epicatechin, rutin, myricetin, and kaempferol (Table 2 ). The main method used was HPLC, but the number and type of flavonoids identified varied according to the methodology used. 

The studies addressed in the present work focused mainly on the pulp of Eugenia fruits, in such a way that only five studies studied the seed, leaves, or peel (Table 2 ). It is observed that for the same fruit, the flavonoid profile can vary according to the part studied, as in work by Gasca et al. (2017) and Silva et al. (2019), who verified, respectively, quercetin in cagaita leaves and vitexin in the pulp. The variation of compounds found can occur even when using the same methodology and part of the fruit, as in Ferreira-Nunes et al. ( 2017 ) and Guedes et al. (2017) studies that evaluate the pulp of cagaita and prove this fact. The first study found catechin through HPLC, while the second discovered epicatechin, quercetin, and rutin using the same methodology. 

Products from cagaita were also addressed. 2021 ) investigated cagaita jelly so that both detected the presence of flavonoids in these food matrices. Rodrigues and his collaborators also evaluated the alteration of the bioactive compounds in the fresh fruit. In the end, they noticed that 78% of the fruit compounds remained in the ice cream after processing. Flavones were also identified in the pulp by Alves et al. (2017) and in the fruit of cagaita by Silva P. R. D. et al. ( 2021 ) and his collaborators. The latter evaluated three progenies of the fruit in different areas of a microregion and concluded that two of them were more promising for future genetic improvements in the species. In this way, it is possible to infer that this class of compounds remains present even through technological processes to develop new products. Souto (2017) found that the flavonoid profile does not change with the development of pitanga fruits. However, a reduction in its content was observed in the red and yellow varieties, compared to the purple one. On the other hand, Borges and Bezerra (2016) characterized the red and purple pitanga pulp and found that most of the bioactive compounds were flavonoids in both colors. In this study, cherry pitanga had a higher concentration of quercetin, and in turn, only myricetin was found in red pitanga. Siebert et al. (2019) studied the inhibitory activity of cherry juice on target enzymes in Alzheimer's and diabetes mellitus treatment and they discovered that, at least in part, the enzyme activity values (52. 67% and 69. 47%, respectively) are related to the presence of flavonoids. Sobral-Souza et al. (2020) concluded that natural compounds from Eugenia uniflora are promising sources of natural products with antioxidant and chelating activity. Rodrigues et al. (2020) found that the combination of furanone with pitanga extract could inhibit the growth of S. liquefaciens, a degrading microorganism of relevance in the dairy industry. Tambara et al. (2018) also evaluated the antioxidant effect of cherry pulp on C. elegans and found that this fruit could protect against oxidative stress genes. Finally, Stafussa et al. (2021) report that the presence of flavonoids in cherry pulp supports preserving its antioxidant and antimicrobial properties during in vitro digestion. 

Eugenia klotzschiana Berg is popularly known as the Cerrado pear. Xavier Mariano et al. (2020), when working with the pulp of this fruit, reported that the paper spray ambient ionization with mass spectrometry technique (PS-MS) is efficient in identifying bioactive compounds present in the pulp, with flavonoids corresponding to 70% of the identified compounds. Although only one work retrieved in this research addressed this fruit, the results of these authors showed that the Cerrado pear has the potential to be exploited. Due to its diversity in chemical composition encompassing bioactive compounds, it can provide an important benefit to human food. 

Regarding Eugenia pyriformis, Farias et al. (2020) determined the antioxidant properties of two fractions of this fruit (edible fraction and seed). They found that the total flavonoid content was approximately 16 times higher in the seed, a fraction that is usually discarded during consumption or processing of the fruit. Rodrigues L. M. et al. (2021) used reverse osmosis to concentrate the bioactive compounds of uvaia residue (seed and peel). They obtained a concentrate 7 to 8 times greater than the control, stimulating its use as a source of antioxidants in the development of functional food formulations, nutraceuticals, or also by pharmaceutical industries. These results also allow us to infer the use of co-products helping to reduce organic waste and possible income generation. Teixeira et al. (2019) investigated changes in urine metabolome after acute ingestion of polyphenol-rich grumixama (Eugenia brasiliensis) juice. HPLC-DAD and LC-ESI-MS/MS identified the main flavonoids as cyanidin 3-Oglucoside and quercetin aglycone, corresponding to 20% and 29% of the total phenolic content, respectively. Fifteen healthy subjects consumed a single dose of grumixama juice in this research, and urine samples were collected before and after Frontiers in Food Science and Technology | www. frontiersin. org ingestion of this juice. The results showed an increase in plasma antioxidant capacity after ingestion and suggest that acute ingestion of grumixama juice may affect amino acid metabolism and mitochondrial metabolism. However, the health-related implications should be explored in further studies. 

Grumixama was chemically characterized through Ramos et al. ( 2020 ) study. By evaluating this fruit's antioxidant potential and chemical profile, it was possible to list 45 compounds using PS-MS. The presence of flavonoids, including catechin and quercetin derivatives, naturally present in grumixama, provides beneficial effects such as antioxidant activity. Nascimento et al. (2017) identified and quantified bioactive compounds, main flavonoids in peel, pulp, and the seed of E. brasiliensis. The peel was the wealthiest part of the fruit concerning this class of compounds. The studies highlight that grumixama has the potential to be used in the food industry, being introduced in food products, additive or natural coloring in products that can promote possible health benefits. 

Nehring (2016) sought to value native species and new sources of chemical compounds with bioactive properties. It was possible to detect 19 compounds, nine flavonoids such as aromadendrin, kaempferol, catechin, epicatechin, hispidulin, quercetin, isoquercetin, taxifolin, and myricetrin. It is possible to observe that catechin and quercetin derivatives are usually detected in E. brasiliensis, highlighting their promising use and beneficial effects on human health, as in work developed by Lazarini et al. (2018) These researchers confirmed the presence of epicatechin and quercetin in the grumixama pulp samples, showed potential antioxidant and anti-inflammatory properties and concluded that the observed anti-inflammatory activity was due to the presence of these compounds. 

Therefore, the Myrtaceae family presented several flavonoids in their chemical profile, especially the fruits mentioned in this study. Those that appeared in greater abundance in the selected works can be highlighted, such as epicatechin, quercetin, rutin, kaempferol, catechin, and myricetin. Thus, these studies highlight the appreciation and importance of species of the genus Eugenia, which promote medicinal properties and beneficial effects on health and possible applicability to the food industry.
section_name: RESULTS AND DISCUSSION

section_content: Therefore, it was possible to observe that among the plants studied, cagaiteira (Eugenia dysenterica) and pitangueira (Eugenia uniflora L) were those that presented the highest return of works related to the identification of flavonoids. Then followed by grumixameira (Eugenia brasiliensis), uvaieira (Eugenia pyriformis Cambess) and Cerrado pear (Eugenia klotzschiana O. Berg). According to the selected works, it is possible to identify that quercetin is the most common flavonoid among the fruits studied. In addition, epicatechin, catechin, kaempferol, and rutin were also evidenced in most of the works discussed. These compounds, in turn, are of great importance for human health as they have biological action already evidenced associated with preventing the emergence of various chronic and degenerative diseases, such as cancer, diabetes, hypertension, Alzheimer's, and cardiovascular diseases, among others. Based on this review, it was possible to observe the importance of plants of the genus Eugenia in terms of the presence and concentration of flavonoids and their main chemical properties with the possibility of application in the development of new products. Therefore, considering the presence of these compounds emphasizes the value and importance of these fruits, making them promising for the food and pharmaceutical industry due to the numerous characteristics and properties they present.
section_name: CONCLUSION

section_name: ACKNOWLEDGMENTS

section_content: The authors would like to thank Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-CAPES, Conselho Nacional de Desenvolvimento Científico e Tecnológico-CNPq, Fundação de Amparo à Pesquisa do Estado de Minas Gerais-FAPEMIG, Universidade Federal de São João Del Rei-UFSJ, Universidade Federal de Minas Gerais-UFMG, Grupo de Ensino de Pesquisa e de extensão em Química e Farmacognosia-GEPEFQ, Instituto Brasileiro de Desenvolvimento e Sustentabilidade-IABS, and Instituto Superior de Agronomia-Universidade de Lisboa for the support.
section_name: ACKNOWLEDGMENTS

section_name: FUNDING

section_content: This research is developed within the framework of the Sustainable Rural Project-Cerrado, funded by Technical Cooperation approved by the Inter-American Development Bank (IDB), with resources from the United Kingdom Government's International Climate Finance, with the Ministry of Agriculture, Livestock, and Supply (MAPA) as the institutional beneficiary. The Brazilian Institute for Development and Sustainability ( IABS-08026000510/2003-51 ) is responsible for the project's execution and administration, and the ILPF Network Association, through Embrapa, is responsible for the scientific coordination and technical support. This research was also developed with the support of Portuguese Foundation for Science and Technology (FCT) through the research unit UID/ AGR/04129/2020 ( Research Center LEAF-Linking Landscape, Environment, Agriculture, and Food).
section_name: FUNDING

section_name: AUTHOR CONTRIBUTIONS

section_content: LN, BN, and YF were responsible for the research, data curation and writing of the original draft. AR and VC were responsible for conceptualization, project management, validation, and writingreviewing and editing. LR and AF were responsible for research and visualization. RF, IS, JM, and PS were responsible for project management and visualization. RA and JM were responsible for project administration, writing-review, editing and resources and conceptualization.
section_name: AUTHOR CONTRIBUTIONS

section_content: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. 

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section_name: Conflict of Interest: