Health benefits of phytochemicals from Brazilian native foods and plants

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<p>Trends in Food Science & Technology 111 (2021) 534–548</p><p>Available online 18 March 2021</p><p>0924-2244/© 2021 Elsevier Ltd. All rights reserved.</p><p>Health benefits of phytochemicals from Brazilian native foods and plants:</p><p>Antioxidant, antimicrobial, anti-cancer, and risk factors of metabolic/</p><p>endocrine disorders control</p><p>Anna Paula Azevedo de Carvalho a,b,c,d,e,**, Carlos Adam Conte-Junior a,b,c,d,e,f,g,*</p><p>a Department of Biochemistry, Institute of Chemistry (IQ), Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro, RJ, 21941-909, Brazil</p><p>b Center for Food Analysis (NAL), Technological Development Support Laboratory (LADETEC), Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de</p><p>Janeiro, RJ, 21941-598, Brazil</p><p>c Laboratory of Advanced Analysis in Biochemistry and Molecular Biology (LAABBM), Department of Biochemistry, Federal University of Rio de Janeiro (UFRJ), Cidade</p><p>Universitária, Rio de Janeiro, RJ, 21941-909, Brazil</p><p>d Graduate Program in Food Science (PPGCAL), Institute of Chemistry (IQ), Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro, RJ,</p><p>21941-909, Brazil</p><p>e Graduate Program in Chemistry (PGQu), Institute of Chemistry (IQ), Federal University of Rio de Janeiro (UFRJ), Cidade Universitária, Rio de Janeiro, RJ, 21941-</p><p>909, Brazil</p><p>f Graduate Program in Veterinary Hygiene (PPGHV), Faculty of Veterinary Medicine, Fluminense Federal University (UFF), Vital Brazil Filho, Niterói, RJ, 24230-340,</p><p>Brazil</p><p>g Graduate Program in Sanitary Surveillance (PPGVS), National Institute of Health Quality Control (INCQS), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, RJ,</p><p>21040-900, Brazil</p><p>A R T I C L E I N F O</p><p>Keywords:</p><p>Bioactive compounds</p><p>Herbal medicine</p><p>Brazilian fruits</p><p>Obesity</p><p>Cancer</p><p>Antiviral</p><p>A B S T R A C T</p><p>Background: Brazil has over 40,000 varied plant species rich in phytochemicals, expressing 20% of the world’s</p><p>flora. Due to its immense diversity, Brazil presents a high potential to produce knowledge and products with</p><p>added value useful in phytomedicine and food supplements to prevent and treat several types of diseases as</p><p>infectious/parasitic, cancer, diabetes, cardiovascular, and others endocrine/metabolic disorders.</p><p>Scope and approach: This comprehensive review focuses on advances in knowledge and understanding of the</p><p>bioactive compounds nature of primary and secondary metabolites of native foods in Brazil. It covers antioxi-</p><p>dant, antimicrobial, antihelmintic, anti-cancer and targets risk factors of metabolic/endocrine disorders by edible</p><p>and non-edible parts of fruit products intake.</p><p>Key findings and conclusions: The Brazilian native flora rich in bioactive compounds exert high inhibition hates (in</p><p>most cases, better than the reference antibiotics) and high selectivity index against several parasites, viruses,</p><p>fungal and bacterias, without cytotoxicity. However, coronaviruses can get more attention. Moreover, several</p><p>endemic species-rich in polyphenols and terpenoids demonstrated cancer cell selectivity, no cytotoxicity to</p><p>healthy cells, and the balance between prooxidant and antioxidant levels that define genomic integrity by cell</p><p>redox status modulation, thus controlling the cancer cells proliferation. Furthermore, oxidative stress and other</p><p>metabolic syndrome risk factors can also be avoided by Brazilian flora. The Cerrado and Pampa fruits received</p><p>significant attention targeting cancer and cardiometabolic/endocrine disorders, while little-explored fruits of</p><p>Caatinga, Amazon, Pantanal and Atlantic forest, rich sources of antioxidants phenolics, flavonoids, poly-</p><p>saccharides, vitamin C, and terpenes, can still generate exciting discoveries, including food packaging solutions.</p><p>* Corresponding author. Departamento de Bioquímica, Instituto de Química, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, 21941-901, Brazil.</p><p>** Corresponding author. Departamento de Bioquímica, Instituto de Química, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, 21941-901,</p><p>Brazil.</p><p>E-mail addresses: anna_paulacarvalho@hotmail.com (A.P.A. Carvalho), conte@iq.ufrj.br (C.A. Conte-Junior).</p><p>Contents lists available at ScienceDirect</p><p>Trends in Food Science & Technology</p><p>journal homepage: www.elsevier.com/locate/tifs</p><p>https://doi.org/10.1016/j.tifs.2021.03.006</p><p>Received 21 December 2020; Received in revised form 1 March 2021; Accepted 2 March 2021</p><p>mailto:anna_paulacarvalho@hotmail.com</p><p>mailto:conte@iq.ufrj.br</p><p>www.sciencedirect.com/science/journal/09242244</p><p>https://www.elsevier.com/locate/tifs</p><p>https://doi.org/10.1016/j.tifs.2021.03.006</p><p>https://doi.org/10.1016/j.tifs.2021.03.006</p><p>https://doi.org/10.1016/j.tifs.2021.03.006</p><p>http://crossmark.crossref.org/dialog/?doi=10.1016/j.tifs.2021.03.006&domain=pdf</p><p>Trends in Food Science & Technology 111 (2021) 534–548</p><p>535</p><p>1. Introduction</p><p>Over the last two decades, the relation between South America’s</p><p>native foods and medicinal effects has been the center of much attention</p><p>(Ciccia et al., 2000; Consolini & Migliori, 2005; Da Silva et al., 2018; V.</p><p>B.; Oliveira et al., 2012). Pilocarpine extracted from Jaborandi (Pilo-</p><p>carpus spp.) is an alkaloid of high medicinal relevance and a few ex-</p><p>amples of natural products without analogies of its high capacity and</p><p>acceptability (Sneader, 2006). Brazil has six major continental biomes</p><p>(Amazon, Atlantic Forest, Cerrado, Caatinga, Pampa, and Pantanal) and</p><p>over 40,000 varied plant species rich in phytochemicals, expressing 20%</p><p>of the world’s flora (V. B. Oliveira et al., 2012), which highlights its</p><p>tremendous potential to produce knowledge and novel products with</p><p>added value, including natural medicine, cosmetics, antimicrobials, and</p><p>food supplements. Recently, in a partnership with Chemical Abstract</p><p>Service (CAS), Brazilian scientists created the first library in Brazil</p><p>(NuBBEDB), and the second-largest database in the world after China,</p><p>detailing chemical and biological information over 54,000 compounds</p><p>from Brazilian biodiversity (Pilon et al., 2017).</p><p>In the last five years, our research group has been dedicated to study</p><p>and report evidence of the importance of polyphenols- and flavonoids-</p><p>rich foods native in Brazil as antioxidant and antimicrobials to</p><p>improve oxidative stability, color, and physicochemical/sensorial</p><p>properties of foods through pequi (Caryocar brasiliensis) and juçara</p><p>(Euterpe edulis) waste extracts, Camu-Camu (Myrciaria dubia) peel and</p><p>seed extracts, and Brazilian pepper (Schinus terebinthifolius Raddi) ex-</p><p>tracts (Fortunato et al., 2019; Frasao et al., 2018; Guedes-Oliveira et al.,</p><p>2018; Moreira et al., 2019). Although its noted potential in food science</p><p>and technology, it has previously been observed that Brazilian native</p><p>vegetables and fruits have ethnopharmacological relevance in phyto-</p><p>medicine. Several isolated compounds, essential oils and plant extracts</p><p>have been commonly used by the indigenous community of Southeast</p><p>and Brazilian Amazon regions to treat infectious illness and show po-</p><p>tential to combat some infectious and parasitic diseases caused by hel-</p><p>minths, bacterias, viruses, fungi and protozoal (Da Silva et al., 2018; M.</p><p>L.; de Mesquita et al., 2007; Gallo et al., 2008; Moura-Costa et al., 2012).</p><p>On the other hand, non-infectious chronic diseases activated by in-</p><p>flammatory pathways as neurodegenerative diseases, carcinogenesis,</p><p>diabetes, obesity, insulin resistance, and nonalcoholic fatty liver dis-</p><p>eases can also benefit from phytomedicine. Natural antioxidants from</p><p>fruits were recently correlated to the inhibition of α-amylase and</p><p>α-glucosidase, one of the therapeutic targets to type 2 diabetes mellitus</p><p>(DM), decreasing the postprandial hyperglycemia (Sun et al., 2020).</p><p>Thereby, Brazilian native foods are excellent sources of antioxidants</p><p>secondary metabolites correlated with carbohydrate-hydrolyzing en-</p><p>zymes (e.g., α-amylase and α-glucosidase); the angiotensin-converting</p><p>enzyme (ACE1 and</p><p>stress have been predictive factors in</p><p>diabetic kidney disease (Jha et al., 2016) and damage in the brain as</p><p>memory dysfunction (Muriach et al., 2014).</p><p>A clinical trial reported the topical treatment with cream (6.0% of</p><p>S. adstringens bark extract) without adverse reactions suppressing the</p><p>hirsutism effect, diminishing terminal hair growth and the number of</p><p>terminal hair (Vicente et al., 2009). Once the hirsutism is understood by</p><p>experts as a result of the conversion of testosterone to the more potent</p><p>androgen 5α-dihydrotestosterone by 5α-reductase (Koulouri & Conway,</p><p>2008), probably, the phytochemicals previously identified in</p><p>S. adstringens (e.g., tannins and flavonoids) (Santos et al., 2002) are</p><p>playing a role in 5α-reductase inhibition, according to similar result</p><p>previously reported for others tannins and flavonoids compounds</p><p>(Bhattacharjee et al., 2011; Kumar & Chaiyasut, 2017). The population</p><p>tested also reported a reduction in skin hyperpigmentation, folliculitis</p><p>and acne (Vicente et al., 2009), which can be a result partially combined</p><p>with a possible antibacterial action against P. acnes previously reported</p><p>for other Brazilian natural sources of flavonoids, polyphenols, and ter-</p><p>penes recently reported (Mustarichie et al., 2020).</p><p>Li et al. (2020) systematically review the data of seven randomized</p><p>controlled trials with 325 participants to assess the antioxidant and</p><p>nutritional potential of ~9.45 g Brazil nuts daily intake/11 weeks. This</p><p>food riched in selenium, vitamin E, and phenolics (e.g., gallic acids and</p><p>ellagic acid) exerts an increase in plasma selenium levels and GPx levels,</p><p>capable of promoting several health benefits as reduce in CVD risks and</p><p>diabetes.</p><p>One fascinating preliminary finding is the capacity of polyphenol-</p><p>rich uvaia juice intake, during eight weeks liver of rats fed a high-fat</p><p>diet, to counter oxidative damage by reduce protein carbonyl levels</p><p>and improve CAT activity (Lopes et al., 2018). Likewise, a clinical trial</p><p>reported that supplementation of 5 g juçara freeze-dried berry pulp</p><p>modulates epigenetic markers in monocytes and improves the blood</p><p>fatty acid profile of obese adults (Santamarina et al., 2018). Recently,</p><p>this research group showed the capacity of 0.50-0.25% polyphenol-rich</p><p>juçara fruit supplementation in avoiding peripheral inflammatory</p><p>pathway activation, body weight gain, and liver injury in a high-fat diet</p><p>of rats (Santamarina et al., 2019). Most recently, the same research</p><p>group confirmed the potential of bioactive compounds of juçara berry</p><p>against the proinflammatory status of obesity through a clinical trial</p><p>with obese adults, showing a reduction in protein expression (TLR4 and</p><p>MYD88 genes) pathways (Santamarina et al., 2020). The researchers</p><p>already understood that the TLR4 receptor plays a vital role in activating</p><p>the inflammatory process of CVD, obesity, metabolic syndrome, and</p><p>insulin resistance (Benomar & Taouis, 2019; Shi et al., 2006; Yu & Feng,</p><p>2018). The supplementation of male mice with babassu mesocarp flour</p><p>during training resistance exerts immunomodulatory effects of lym-</p><p>phocytes and macrophages, cytokine production, and reduction of</p><p>A.P.A. Carvalho and C.A. Conte-Junior</p><p>Trends in Food Science & Technology 111 (2021) 534–548</p><p>545</p><p>Fig. 2. Bioactive compounds-rich foods in Brazil to endocrine/metabolic disorders control: targeting oxidative stress response pathways.</p><p>A.P.A. Carvalho and C.A. Conte-Junior</p><p>Trends in Food Science & Technology 111 (2021) 534–548</p><p>546</p><p>cholesterol and triglycerides levels (Soares et al., 2020). Thereby, these</p><p>results highlight the potential of cited Brazilian native fruits dietary as a</p><p>source of natural antioxidants (rich in dietary fiber, fatty acids, and</p><p>anthocyanins) in the inflammatory modulation and prevention of CVD,</p><p>which is one of the chronic metabolic diseases of higher mortality rate in</p><p>the world (World Health Organization, 2020). We summarized in Fig. 2</p><p>the main antioxidant-rich foods/plants in Brazil targeting oxidative</p><p>stress response pathways, potential as attempts for several endo-</p><p>crine/metabolic disorders control.</p><p>4. Conclusions and outlook</p><p>The Brazilian native fruits and plants are rich sources of primary and</p><p>secondary metabolites as fatty acids, dietary fibers, hetero-</p><p>polysaccharides, carbohydrates, flavonoids, polyphenols, terpenoids,</p><p>alkaloids, tocopherols, coumarins and phenolic acids both in edible and</p><p>non-edible parts (as waste and agro-industrial co-products), which</p><p>highlighted its relevance in food supplementation and products with</p><p>added value as cosmetics, herbal medicines and pest control substances</p><p>for agriculture. Based on evidence reported here, the high selectivity for</p><p>cancer cells with no cytotoxicity to normal cells suggests the potential of</p><p>natural bioactive compounds of Brazilian native diversity (e.g., poly-</p><p>phenols, fatty acids and terpenoids) to develop novel chemotherapeutic</p><p>drugs for cancer treatment considering breast cancer, colorectal cancer,</p><p>skin carcinoma. High inhibition hates with high selective index, and low</p><p>cytotoxicity was discussed for several pathogens causative illness in</p><p>humans better than reference antibiotics, fungicides and antihelmintic.</p><p>The oxidative damage, cell redox balance (antioxidant/prooxidant</p><p>levels), and activation of detoxified enzyme expression are intimately</p><p>connected with tumor cells selectivity and risk factors of metabolic</p><p>syndrome and endocrine disorders as diabetes/obesity and its compli-</p><p>cations. We noted health benefits by several types of food supplemen-</p><p>tation: dietary fibers, fresh fruit, freeze dried-juice, fresh juice, extracts,</p><p>or oils.</p><p>The Cerrado and Pampa fruits received significant attention target-</p><p>ing cancer and cardiometabolic/endocrine disorders, while little-</p><p>explored native edible fruits of Brazil’s Caatinga, Pantanal and</p><p>Atlantic forest, rich sources of antioxidants phenolics, flavonoids,</p><p>polysaccharides, vitamin C, terpenes, and bioaccessible polyphenols</p><p>after digestion can still generate exciting discoveries. For example,</p><p>Vitamin C content in P. glomerata (of Pantanal) freeze-dried was four-</p><p>time of orange juice. Perhaps the investigation of synergism between</p><p>phytochemicals rich-fruits from different Brazilian biomes brings novel</p><p>insights into the development of novel chemotherapies attempts.</p><p>Complementary investigations could be realized to address the</p><p>mechanism of antiparasitic, anti-diabetic, antiproliferative, and anti-</p><p>microbial actions to provide a better understatement of the medicinal</p><p>effects of Brazilian foods. We also hope that bioactive compounds of</p><p>Brazilian foods and plants could be studied against other viruses, like</p><p>novel coronavirus and the concept be extended to food packaging</p><p>technology as smart and active food packagings.</p><p>CRediT authorship contribution statement</p><p>Anna Paula Azevedo de Carvalho: Conceptualization, Formal</p><p>analysis, Investigation, Writing – original draft, Project administration.</p><p>Carlos Adam Conte-Junior: Conceptualization, Supervision, Writing –</p><p>review & editing.</p><p>Declaration of competing interest</p><p>The authors declare no conflict of interest.</p><p>Acknowledgments</p><p>This work was supported by Fundação Carlos Chagas Filho de</p><p>Amparo ̀a Pesquisa do Estado do Rio de Janeiro – Brasil (FAPERJ) [grant</p><p>number E-26/2543334/2019, E-26/010.000.984/2019, E-26/</p><p>010.000148/2020, and E-26/200.060/2020]; and the Conselho Nacio-</p><p>nal de Desenvolvimento Científico e Tecnológico - Brasil (CNPq) [grant</p><p>number 311422/2016-0].</p><p>References</p><p>Abrão, F., de Araújo Costa, L. 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The ACE1 was implicated in</p><p>Alzheimer’s disease (Miners et al., 2009), ACE2 was identified as the</p><p>receptor for the SARS-CoV-2 viral entry (Samavati & Uhal, 2020), and</p><p>5-alpha-reductase implicated in hirsutism in women (Koulouri & Con-</p><p>way, 2008).</p><p>Oxidative damage and inflammatory responses are known to play an</p><p>essential role in neuronal damage, in the development of both micro-</p><p>vascular and cardiovascular complications of diabetes (e.g., neuropathy,</p><p>retinopathy and nephropathy) (Giacco & Brownlee, 2010), triggering</p><p>obesity-related complications by stimulating the adipose tissue</p><p>dysfunction (Manna & Jain, 2015), metabolic syndrome risk factors,</p><p>which has been correlated to increased risk of cardiovascular diseases</p><p>(CVD), DM, and renal disease. These included hypertension, hypergly-</p><p>cemia, visceral fat, high levels of triglycerides and bad cholesterol</p><p>(Francini-Pesenti et al., 2019). Thus, Brazilian dietary fruits, rich sour-</p><p>ces of bioactive compounds, show great potential as anti-diabetic foods</p><p>to diabetic patients. Moreover, as secondary metabolites of plant species</p><p>are antioxidants capable of regulating the cellular redox homeostasis,</p><p>balancing the levels of reactive oxygen/nitrosative species (ROS/NRS)</p><p>production and scavenging, the Brazilian native flora, rich in phenolic</p><p>compounds and terpenoids, showed interest in vitro antiproliferative</p><p>effects without cytotoxicity to regular cell lines (Colombo et al., 2015;</p><p>dos Reis et al., 2020; Seraglio et al., 2018; Zhang & Tsao, 2016).</p><p>Table 1</p><p>Brazilian native biomes as a source of food/plants rich in phytochemicals in</p><p>studies overviewed.</p><p>Specie Plant/Food Family Origin/biome</p><p>in Brazil</p><p>Anacardium occidentale L. Cashew apple Anacardiaceae Caatinga</p><p>Ananas comosus L. Pineapple Bromeliaceae Southern</p><p>Annona coriacea Mart. Araticum Annonaceae Cerrado</p><p>Araucaria angustifolia</p><p>(Bert.) O. Ktze.</p><p>Paraná pine Araucariaceae Pampa</p><p>Aspidosperma macrocarpon</p><p>Mart.</p><p>Peroba Apocynaceae Cerrado</p><p>Attalea speciosa syn</p><p>Orbignya phalerata Mart.</p><p>Babassu Arecaceae Amazon</p><p>Baccharis dracunculifolia Alecrim-do-</p><p>campo</p><p>Asteraceae Cerrado</p><p>Bertholletia excelsa Brazil nut Lecythidaceae Amazon</p><p>Butia eriospatha Butiá Arecaceae Atlantic Forest</p><p>Campomanesia eugenioides</p><p>Cambess.</p><p>Gabiroba Myrtaceae Cerrado</p><p>Campomanesia phaea (O.</p><p>Berg.)</p><p>Cambuci Myrtaceae Atlantic Forest</p><p>Caryocar Brasiliense Camb. Pequi Caryocaraceae Cerrado</p><p>Casearia sylvestris Guaçatonga Salicaceae Cerrado</p><p>Copaifera langsdorffii Copaíba Fabaceae Cerrado</p><p>Cordia americana L. Guajuvira Boraginaceae Pampa</p><p>Curatella americana L. Lixeira Dilleniaceae Cerrado</p><p>Eugenia brasiliensis Lam. Grumixama Myrtaceae Atlantic Forest</p><p>Eugenia dysenterica DC. Cagaita Myrtaceae Cerrado</p><p>Eugenia klotzschiana Berg. Pêra-do-</p><p>cerrado</p><p>Myrtaceae Cerrado</p><p>Eugenia uniflora L. Brazilian cherry Myrtaceae Pampa</p><p>Eugenia uvaia cambess Uvaia Myrtaceae Cerrado</p><p>Euterpe edulis Mart. Juçara Arecaceae Atlantic Forest</p><p>Hancornia speciosa Mangaba Apocynaceae Caatinga</p><p>Malpighia emarginata DC. Acerola Malpighiaceae Caatinga</p><p>Manihot esculenta Crantz Cassava</p><p>(manioc)</p><p>Euphorbiaceae Cerrado</p><p>Myrciaria cauliflora Berg. Jabuticaba Myrtaceae Atlantic Forest</p><p>Myrciaria dubia Mc. Vaugh Camu-Camu Myrtaceae Amazon</p><p>Myrciaria jaboticaba</p><p>(Vell.) O. Berg</p><p>Jabuticaba Myrtaceae Cerrado,</p><p>Atlantic Forest</p><p>Ocimum gratissimum L. Wild basil Lamiaceae Atlantic Forest</p><p>Passiflora cincinnata Mast. Passion fruit</p><p>“do Mato"</p><p>Passifloraceae Caatinga</p><p>Passiflora edulis Sims Passion fruit Passifloraceae Cerrado</p><p>Passiflora tenuifila Killip Garlic passion</p><p>fruit</p><p>Passifloraceae Cerrado</p><p>Pilocarpus pennatifolius</p><p>Lem.</p><p>Jaborandi Rutaceae Amazon,</p><p>Pampa</p><p>Pouteria glomerata (Miq.)</p><p>Radlk</p><p>Laranjinha de</p><p>pacu</p><p>Sapotaceae Cerrado,</p><p>Pantanal</p><p>Pouteria ramiflora Curriola Sapotaceae Cerrado</p><p>Pouteria torta Abiu Sapotaceae Cerrado</p><p>Psidium cattleianum Sabine Araçá Myrtaceae Pampa</p><p>Rubus spp. Blackberries Rosaceae Cerrado</p><p>Schinus terebinthifolius</p><p>Raddi</p><p>Pink pepper Anacardiaceae Atlantic Forest</p><p>(Restinga)</p><p>Simarouba versicolor Pau-paraíba Simaroubaceae Cerrado</p><p>Spondias purpurea L. Siriguela Anacardiaceae Caatinga,</p><p>Cerrado</p><p>Spondias spp. Umbu-cajá Anacardiaceae Caatinga</p><p>Spondias tuberosa A. Umbu Anacardiaceae Caatinga</p><p>Stryphnodendron</p><p>adstringens</p><p>Barbatimão Fabaceae Cerrado</p><p>Theoboma grandiflorum Cupuaçu Sterculiaceae Amazon</p><p>Vitex polygama Tarumã do</p><p>cerrado</p><p>Verbenaceae Cerrado</p><p>Zanthoxylum rhoifolium</p><p>Lam.</p><p>Mamica-de-</p><p>cadela</p><p>Rutaceae Cerrado</p><p>A.P.A. Carvalho and C.A. Conte-Junior</p><p>Trends in Food Science & Technology 111 (2021) 534–548</p><p>536</p><p>Table 2</p><p>Natural bioactive compounds derived from Brazilian native foods with antioxidant activity.</p><p>Specie Brazilian fruit Part/Form product Antioxidant</p><p>activity</p><p>Phytochemicals associated Ref.</p><p>A. Angustifolia Paraná pine Waste bracts (extract) IC50: 0.146 mg.</p><p>AA/ml</p><p>Catechin, epicatechin, quercetin, and apigenin. (M. Souza et al.,</p><p>2014)</p><p>A. comosus Pineapple Co-products</p><p>(polysaccharide</p><p>fractions)</p><p>IC50 = 80 μM.TE/</p><p>g</p><p>Arabinogalactans Bruno de Sousa</p><p>Sabino et al. (2020)</p><p>A. occidentale Cashew apple IC50 = 147 μM.</p><p>TE/g</p><p>B. eriospatha Butia Edible-portions fruit</p><p>(extracts)</p><p>IC50: 253.8 mg.</p><p>AA/ml</p><p>Gallic acid, protocatechuic acid, caffeic acid, chlorogenic</p><p>acid, isoquercitrin, and quercetin derivatives; hyperoside,</p><p>and rutin.</p><p>Denardin et al.</p><p>(2015)</p><p>C. brasiliense Pequi Fruit peel waste</p><p>(ethanol extract)</p><p>94%A,C Phenolic compounds, flavonoids, and anthocyanins Frasao et al. (2018)</p><p>C. brasiliense Pequi Pulp oil (Alcoholic</p><p>extract)</p><p>EC50 = 26 μg/MlB,</p><p>C</p><p>Palmitic and oleic acids, α-tocopherol, β-carotene, and</p><p>lycopene.</p><p>Roll et al. (2018)</p><p>C. brasiliense Pequi Leaves (ethyl acetate</p><p>fraction)</p><p>IC50 = 4.6 μg/mL Gallic acids and quercetin (T. S. de Oliveira</p><p>et al., 2018)</p><p>C. phaea Cambuci Frozen pulp (Juice) 0.98 mmol.TE/</p><p>100 mL</p><p>Proanthocyanidins Balisteiro et al.</p><p>(2017)</p><p>E. dysenterica Cagaita 1.04 mmol.TE/</p><p>100 mL</p><p>Proanthocyanidins</p><p>E. klotzschiana Pêra-do-</p><p>Cerrado</p><p>Leaves and flowers (EO) IC50: 5.7–29.7 μg/</p><p>mL</p><p>Germacrene-D and eugenol Carneiro et al.</p><p>(2017)</p><p>E. uniflora Brazilian cherry Edible-portions fruit</p><p>(extracts)</p><p>IC50: 36.8–121.9</p><p>mg.AA/ml</p><p>Gallic acid, quercetin, quercitrin, isoquercitrin, kaempferol</p><p>derivatives; and cyanidin-3-glucoside</p><p>Denardin et al.</p><p>(2015)</p><p>E. uvaia Uvaia Fresh fruit (juice) 94.93% at 200</p><p>mg/L D, E</p><p>Total phenolic content: 135 mg GAE/100 g per juice Lopes et al. (2018)</p><p>G. americana Genipap Peel (extract) 15.4%D Leucoanthocyanidins, catechins and flavanones;</p><p>Anthraquinones, anthrones and coumarins; Triterpenoids,</p><p>sterols.</p><p>Omena et al.</p><p>(2012)</p><p>H. speciosa Mangaba Frozen pulps (in vitro</p><p>digestion)</p><p>1907 μmol.TE/</p><p>100 g</p><p>1870 Fe+ 2/100 g</p><p>Bioacessible phenolics: rutin, hesperetin and vanillic acid. Dutra et al. (2017)</p><p>M. emarginata Acerola Co-products</p><p>(polysaccharide</p><p>fractions)</p><p>IC50 = 79 μM.TE/</p><p>g</p><p>Arabinogalactans Bruno de Sousa</p><p>Sabino et al. (2020)</p><p>M. dubia Camu-Camu Frozen pulp (juice) 6.4 mmol.TE/100</p><p>mL</p><p>Phenolics Balisteiro et al.</p><p>(2017)</p><p>M. jaboticaba Jabuticaba 2.54 mmol.TE/</p><p>100 mL</p><p>Phenolics, proanthocyanidins</p><p>M. jaboticaba Jabuticaba Lyophilized jabuticaba</p><p>seed extract</p><p>31,338 mg.GAE/</p><p>100 gF</p><p>Castalagin, vescalagins, procyanidin A2, gallic and ellagic</p><p>acids.</p><p>Fidelis et al. (2021)</p><p>P. cattleianum Araçá fruit (acetone extract) 45%/85%D (-)-Epicatechin and gallic acid. Medina et al.</p><p>(2011)</p><p>P. cattleianum Araçá Edible-portions fruit</p><p>(extracts)</p><p>IC50: 48.1 mg.AA/</p><p>ml</p><p>Gallic acidquercetin, apigenin derivatives; and</p><p>isoquercitrin.</p><p>Denardin et al.</p><p>(2015)</p><p>P.</p><p>cincinnata Passion fruit</p><p>“do Mato”</p><p>Pulp oil IC50 = 0.42 mg/</p><p>mlC</p><p>Quercetin, naringenin, and gallic acid. Ribeiro et al.</p><p>(2020)</p><p>P. cincinnata Mast cv.</p><p>BRS Sertão Forte</p><p>Passion fruit</p><p>“do Mato"</p><p>Mature pulp 167 μmol Fe+2/</p><p>100 g</p><p>Caftaric acid, isoquercetin, and rutin de Souza Silva et al.</p><p>(2020)</p><p>Intermediate maturing</p><p>pulp</p><p>231 μmol Fe+2/</p><p>100 g</p><p>Caftaric acid and isoquercetin</p><p>P. edulis Passion fruit Co-products</p><p>(polysaccharide</p><p>fractions)</p><p>IC50 = 8 μM.TE/g Arabinogalactans Bruno de Sousa</p><p>Sabino et al. (2020)</p><p>P. tenuifila Garlic passion</p><p>fruit</p><p>Frozen pulp (juice) 0.88 mmol.TE/</p><p>100 mL</p><p>Proanthocyanidins Balisteiro et al.</p><p>(2017)</p><p>P. glomerata Laranjinha-de-</p><p>Pacu</p><p>Peel and pulp of freeze-</p><p>dried (extracts)</p><p>6416-40,707</p><p>mmol.TE/100 g</p><p>Phenolics and vitamin C do Espirito Santo</p><p>et al. (2020)</p><p>P. ramiflora Curriola Leaves (ethyl acetate</p><p>fraction)</p><p>150%B, C Triterpenes: Friedelin</p><p>Epi-friedelanol, and Taraxerol.</p><p>Rodrigues et al.</p><p>(2017)</p><p>P. torta Abiu Epicarp (fractions and</p><p>crude extract)</p><p>283%B, A Phenolics and flavonoids de Sales et al.</p><p>(2017)</p><p>Rubus spp. Blackberries Edible-portions fruit</p><p>(extracts)</p><p>IC50: 44.7–78.5</p><p>mg.AA/ml</p><p>Ellagic acid and quercetin derivatives; isoquercitrin;</p><p>cyanidin-3-glucoside, and delphinidin derivatives.</p><p>Denardin et al.</p><p>(2015)</p><p>S. adstringens Barbatimão Leaf (aqueous fractions) IC50 = 6.7 mg/mL Gallic acid, procyanidin dimer B1, and epicatechin gallate. Sabino et al. (2018)</p><p>Spondias spp. Umbu-cajá Frozen pulps (in vitro</p><p>digestion)</p><p>5066 μmol.TE/</p><p>100 g</p><p>1271 Fe+ 2/100 g</p><p>Bioacessible phenolics: trans-cinnamic and gallic acids, and</p><p>catechins.</p><p>Dutra et al. (2017)</p><p>S. tuberosa Umbu Seeds (extract) 20.8%D Phenols and tannins; leucoanthocyanidins, catechins and</p><p>flavanones; anthraquinones,</p><p>anthrone and coumarins; triterpenoids and steroids.</p><p>Omena et al.</p><p>(2012)</p><p>S. Purpurea Siriguela Seeds (extract) 37.6%D Phenols and tannins; leucoanthocyanidins, catechins and</p><p>flavanones; anthraquinones,</p><p>Omena et al.</p><p>(2012)</p><p>(continued on next page)</p><p>A.P.A. Carvalho and C.A. Conte-Junior</p><p>Trends in Food Science & Technology 111 (2021) 534–548</p><p>537</p><p>In this context, this comprehensive review focuses on the knowledge</p><p>of the antioxidants-rich fruits/vegetables native in Brazil and their</p><p>antimicrobial, antihelmintic, and antiproliferative activities and their</p><p>effects on risk factors of metabolic/endocrine disorders control. We</p><p>attempt to defend the view that several phytochemicals from both edible</p><p>and non-edible parts of foods and endemic species of Brazil can play an</p><p>essential role in the prevention and treatment of several human condi-</p><p>tions both from the development of novel drugs (with higher selectivity</p><p>and fewer side effects) and from human dietary supplementation, due to</p><p>its high antioxidant nature. We proposed a link between antioxidants</p><p>and cellular redox homeostasis and oxidative stress to prevent and</p><p>control the risks in carcinogenesis and risk factors of metabolic/endo-</p><p>crine disorders.</p><p>2. Search methods</p><p>The studies related to antioxidants and medicinal effects derived</p><p>from Brazilian native fruits were retrieved by literature searching in</p><p>Science Direct and PubMed/MEDLINE with the following keywords and</p><p>synonyms: “Brazilian fruits” or “Brazilian foods” or “Brazilian biodi-</p><p>versity”, including the common name and specie of fruits of “Cerrado”,</p><p>“Amazon” and others biomes; “antimicrobials” and “antioxidants”</p><p>related to “diabetic”, “obesity”, “endocrine”, “cancer”, “herbal medi-</p><p>cine”. We categorized studies in the function of the common name, plant</p><p>specie, phytochemicals screened and the most productive biome, ac-</p><p>cording to NuBBEDB (http://nubbe.iq.unesp.br/portal/nubbe-search.</p><p>html) or the library “Digital Flora of Rio Grande do Sul and Santa Cat-</p><p>arina States” (https://floradigital.ufsc.br/).</p><p>3. Main findings: Brazilian native food/plants rich in</p><p>antioxidants</p><p>Table 1 displayed the 33 fruits, and 16 plant species rich in phyto-</p><p>chemicals native in Brazil reviewed in this article in the function of</p><p>family and highest occurring biome/region. We highlight Cerrado</p><p>(Brazilian Savannah), Brazil’s Atlantic Forest, Amazon rainforest, Caa-</p><p>tinga, Pantanal, and Pampa, among other specific regions and vegeta-</p><p>tions (e.g., Restinga of Atlantic forest) of the most frequent occurrence.</p><p>Pantanal is predominantly in the Midwest and little-known around the</p><p>world. The ‘Cerrado’ is the Brazilian Savannah, and ‘Caatinga’ is arid</p><p>and semiarid vegetation located in Brazil’s Northeast. 60% of the</p><p>Amazon basin is in Brazil, in which we discussed the health benefits of 4</p><p>species of native fruits. The south and southeast regions were also</p><p>highlighted by several plants and fruits with high ethnopharmaceutical</p><p>and ethnomedicine relevance of Cerrado. The Pampa, located in the</p><p>southernmost region, was also highlighted. Different parts of the plant as</p><p>edible fruits, native fruits, and non-edible parts of fruits (e.g., mesocarp,</p><p>epicarp, seeds, and peels), dietary fibers, and other plant parts (e.g.,</p><p>seeds, roots, leaves, flowers, stems) were studied by several authors and</p><p>presented antimicrobial and antiparasitic activity, antioxidant activity,</p><p>anti-diabetic, antiproliferative, anti-obesity, and other health improve-</p><p>ments considering the metabolic and endocrine system through in vitro,</p><p>in vivo, and clinical trials studies. Of these, was addressed the main</p><p>phytochemicals often chemical characterized and discussed in the pa-</p><p>pers reviewed, considering isolated compounds, extracts and fractions,</p><p>essential oils, flours, and fruit juices. It covers heteropolysaccharides,</p><p>lipids, terpenoids, phenolic compounds, alkaloids, and other nitrogen-</p><p>containing metabolites.</p><p>3.1. Antioxidant activity</p><p>The extracts of tropical Brazilian fruits rich in phenolic acids have</p><p>been recommended for human dietary supplements and cosmetic/</p><p>pharmaceutical industries due to their high antioxidant capacity.</p><p>Table 2 compares the relationship between antioxidant activity and</p><p>natural phytochemicals derived from Brazilian native foods and exotic</p><p>plants. These findings lay out important insights into the role of the</p><p>antioxidant capacity of Brazilian edible fruits, native plant leaves, food</p><p>co-products and wastes (e.g., peels, seeds, endocarps, mesocarps, and</p><p>epicarps) in reason of its complex chemical constitution rich in a wide</p><p>diversity of primary and secondary metabolites as lipids, carbohydrates,</p><p>phenolics, carotenoids, vitamins, and terpenoids.</p><p>The literature related the high antioxidant capacity of extracts ob-</p><p>tained from non-edible portions of Genipa americana (genipap), Spondias</p><p>Purpurea L. (commonly known as “siriguela”), and Spondias Tuberosa A.</p><p>(umbu) (seeds and peel) as phenolic acids (i.e., quercetin, citric and</p><p>quinic acids, and chlorogenic acids). The antioxidant, anti-</p><p>acetylcholinesterase and cytotoxic activities in exotic fruits were</p><p>shown from the ethanolic extract and were correlated with the main</p><p>content of phenolic acids. All fruits tested presented high antioxidant</p><p>capacity. The extracts of genipap pulp and siriguela seeds presented no</p><p>cytotoxicity on sheep corneal epithelial cells and highest acetylcholin-</p><p>esterase inhibition, similarly to carbachol positive control (Omena et al.,</p><p>2012). Moreover, Spondias spp. (traditionally known as “umbu-cajá"), S.</p><p>Purpurea and Hancornia speciosa (known as “mangaba”), three native</p><p>fruits of the northeast Brazilian region, contain phenolic compounds</p><p>with high antioxidant capacity after exposure to simulated gastrointes-</p><p>tinal conditions: the highest antioxidant capacity to capture DPPH</p><p>radicals or iron ion reducing was accessed for phenolics in dialysate</p><p>frozen pulps (Dutra et al., 2017). Additionally, the phenolics of Spondias</p><p>spp., S. Purpurea</p><p>L. (i.e., trans-cinnamic acids, gallic acid, and cate-</p><p>chins.), and phenolics of H. speciosa (i.e., rutin, hesperetin and vanillic</p><p>acid) presented bioaccessibility after in vitro digestion (Dutra et al.,</p><p>2017).</p><p>Similarly, antioxidant capacity was attributed to gallic acid, quer-</p><p>cetin, quercitrin, isoquercitrin, and cyanidin derivatives present in the</p><p>extracts of the edible portions of some fruits grown in the southeast of</p><p>Brazil as Eugenia uniflora (Brazilian cherry), Rubus sp. (Blackberries), and</p><p>Butia eriospatha (butiá) (Denardin et al., 2015), and Psidium cattleianum</p><p>(araçá) (Denardin et al., 2015; Medina et al., 2011).</p><p>The Paraná pine Araucaria angustifolia (Bert.) O. Kuntze (commonly</p><p>known as “araucária"), one of the essential plant specie of the south</p><p>Brazilian region, was chemically characterized in terms of phenolic</p><p>profile presenting a high content of phenolic compounds (i.e., gallic</p><p>Table 2 (continued )</p><p>Specie Brazilian fruit Part/Form product Antioxidant</p><p>activity</p><p>Phytochemicals associated Ref.</p><p>anthrone and coumarins; triterpenoids and steroids;</p><p>saponins.</p><p>S. purpurea Siriguela Frozen pulps (in vitro</p><p>digestion)</p><p>4985 μmol.TE/</p><p>100 g</p><p>1141 Fe+ 2/100 g</p><p>Bioacessible phenolics: trans-cinnamic and gallic acids, and</p><p>catechins.</p><p>Dutra et al. (2017)</p><p>T. grandiflorum Cupuaçu Frozen pulp (juice) 0.85 mmol.TE/</p><p>100 mL</p><p>Phenolics, proanthocyanidins Balisteiro et al.</p><p>(2017)</p><p>IC50: concentration to 50% antioxidant activity; TE: Trolox equivalents; AA: ascorbic acid equivalents; GAE: gallic acid equivalents; A: in comparison BHT positive</p><p>control; B: phosphomolybdenum method; C: in comparison ascorbic acid control; D: DPPH radical-scavenging test; E: in comparison 700 mg.TE/L control; F: Folin-</p><p>Ciocalteu reducing capacity.</p><p>A.P.A. Carvalho and C.A. Conte-Junior</p><p>http://nubbe.iq.unesp.br/portal/nubbe-search.html</p><p>http://nubbe.iq.unesp.br/portal/nubbe-search.html</p><p>https://floradigital.ufsc.br/</p><p>Trends in Food Science & Technology 111 (2021) 534–548</p><p>538</p><p>acid, catechin, epicatechin, quercetin, and apigenin) in non-edible parts</p><p>and a potent antioxidant activity with an IC50 of 0.146 mg/mL for 125</p><p>μM of lyophilized powder of bract extract (M. Souza et al., 2014).</p><p>Another native edible fruit grown in the south and southeast region of</p><p>Brazil with relevant potential to phytotherapy is Eugenia uvaia cambess</p><p>(commonly know as “uvaia”) that given its improved antioxidant effi-</p><p>ciency of 94.93% in comparison 700 mg/L Trolox control and attenua-</p><p>tion of oxidative damage to proteins was suggested for prevention of</p><p>chronic metabolic diseases (Lopes et al., 2018).</p><p>The use of ultrasound-assisted extraction (UAE) technique led to</p><p>better oil yield and quality due to the better penetration of solvent in</p><p>plant materials, while the typical methods using stirring/solvent</p><p>extraction usually need long-time extraction and might lead to degra-</p><p>dation of phytochemicals retrieved. For example, the UAE of pulp oil</p><p>from Passiflora cincinnata Mast., the passion fruit from Caatinga biome</p><p>located in a semiarid region, showed antioxidant activity with IC50 0.42</p><p>mg/mL with total phenolic contents of 854.92 mg.GAE/100 g, where the</p><p>main phenolics are quercetin, naringenin, and gallic acid (Ribeiro et al.,</p><p>2020). On the other hand, the use of typical extraction of the</p><p>intermediated mature stage pulp of P. cincinnata Mast cv. BRS Sertão</p><p>Forte (a new variety of passion fruit “da Caatinga”) with total phenolic</p><p>content of 53.5 mg.GAE/100 g, were isoquercetin (32.25 μg/g) and</p><p>caftaric acid (7.5 μg/g) as the major phenolics in the pulp responsible for</p><p>the antioxidant activity of 316 μmol. Trolox/100 g measured by DPPH</p><p>assay (de Souza Silva et al., 2020).</p><p>Polyphenol (e.g., eugenol) and sesquiterpene (e.g., germacrene D)</p><p>were the main phytochemicals correlated with antioxidant activity</p><p>(DPPH: IC50 = 5.7–29.7 μg/mL) investigated for essential oils from</p><p>leaves and flowers of Eugenia klotzschiana Berg. (known as pêra-do-</p><p>cerrado) (Carneiro et al., 2017). The phenolics and flavonoids com-</p><p>pounds in ethyl acetate fraction of epicarp extract of Pouteria torta (a</p><p>native fruit of Cerrado knows as abiu) were attributed to 283% antiox-</p><p>idant activity in comparison synthetic butylated hydroxytoluene (BHT)</p><p>positive control accessed through phosphomolybdenum assay (de Sales</p><p>et al., 2017). The antioxidant activity values reported for ethyl acetate</p><p>fraction of leaf extract of Pouteria ramiflora (popularly known as “cur-</p><p>riola”) highlight the medicinal potential of triterpenes as friedelin (iso-</p><p>lated for the first time from Pouteria spp.), epi-friedelanol, and taraxerol</p><p>Table 3</p><p>Antimicrobial activity of Brazilian native plant species rich in phytochemicals.</p><p>Specie Brazilian fruit/</p><p>plant</p><p>Form of fruit product Microorganism Dosage Inhibition</p><p>Effect</p><p>Ref.</p><p>Antiviral activity</p><p>B. dracunculifolia Alecrim-do-</p><p>campo</p><p>Green propolis (butanoic</p><p>fraction)</p><p>HSV-1 MIC:100 μg/mL 90% Hochheim et al.</p><p>(2019) MIC: 58.5 μg/mL 50%</p><p>C. americana Guajuvira Barks (70% HAE) HSV-1 – EC50 = 4.5</p><p>μg/ml, SI = 55</p><p>Moura-Costa et al.</p><p>(2012)</p><p>Barks (crude extract) Poliovirus 10, 50, 100, 500, and</p><p>1000 μg/mL</p><p>EC50 = 49 μg/mL de Toledo et al.</p><p>(2011)</p><p>O. gratissimum Wild basil Whole plant (50% HAE) Poliovirus – EC50 = 12 μg/mL, SI</p><p>= 40.3</p><p>Moura-Costa et al.</p><p>(2012)</p><p>V. polygama Tarumã do</p><p>cerrado</p><p>Fruits (ethyl acetate extract) Acyclovir-resistant</p><p>HSV-1</p><p>25 μg/mlb 85.2% Gonçalves et al.</p><p>(2001) leaves (ethyl acetate extract) 50 μg/mlb 73.7%</p><p>Antifungal activity</p><p>C. americana Guajuvira Bark (crude extract and acetyl</p><p>acetate fraction)</p><p>C. albicans</p><p>C. parapsilosis</p><p>MIC = 31.3 μg/mL – de Toledo et al.</p><p>(2011)</p><p>C. eugenioides Gabiroba Leave (HAE) Candida spp. MIC = 0.24 μg/mL SI = 120.8 Moura-Costa et al.</p><p>(2012)</p><p>E. dysenterica Cagaita leafs (EO) C. neoformans (strains) MICs≥3.12 μg/mL 91.6%A, 50%B and</p><p>30%C</p><p>(T. R. Costa et al.,</p><p>2000)</p><p>P. pennatifolius Jaborandi Dimethyl allyl xanthyletin</p><p>(isolated)</p><p>C. krusei MIC = 15.6 μg/mL – do Carmo et al.</p><p>(2018)</p><p>Jaborandine (isolated) MIC = 1.56 μg/mL –</p><p>Pennatifoline A (isolated) MIC = 3.12 μg/mL –</p><p>S. terebinthifolius Pink pepper Bark (HAE) Candida spp. MIC = 0.49 μg/mL SI = 104.1 Moura-Costa et al.</p><p>(2012)</p><p>Antibacterial activity</p><p>A. speciosa Babassu Mesocarp (ethanolic extract) E. faecalis (ATCC</p><p>29212)</p><p>MIC: 31.2 mg/mLD – Barroqueiro et al.</p><p>(2016)</p><p>S. aureus (ATCC 25923) MIC: 31.2 mg/mLD –</p><p>MRSAE (hospital strain) MIC:7.8 mg/mLD –</p><p>E. klotzschiana Pêra-do-</p><p>cerrado</p><p>Leaves and flowers (EO) S. salivarius (ATCC</p><p>25975)</p><p>MIC: 200 μg/mL 100% Carneiro et al.</p><p>(2017)</p><p>S. mutans (ATCC</p><p>25175)</p><p>MIC:50 μg/mL 100%</p><p>S. mitis (ATCC 25175) MIC:200 μg/mL 100%</p><p>P. nigrescens (ATCC</p><p>33563)</p><p>MIC:50 μg/mL 100%</p><p>M. esculenta Cassava Leaves (ethyl acetate fractions) S. epidermidis (clinical</p><p>isolates)</p><p>MIC: 2.5%–5.0% (w/v) – Mustarichie et al.</p><p>(2020) MBC: 5% (w/v) –</p><p>P. acnes (clinical</p><p>isolates)</p><p>MIC: 1.25%–2.5% (w/v) –</p><p>MBC: 2.5% (w/v) –</p><p>P. cattleianum Araçá Fruit (extracts) S. enteritidis (ATCC</p><p>13076)</p><p>MIC:5% 69% Medina et al. (2011)</p><p>P. pennatifolius Jaborandi Xanthotoxin (isolated) S. flexneri MIC:3.12 μg/mL – do Carmo et al.</p><p>(2018) Pennatifoline A (isolated) E. fecalis MIC:1.56 μg/mL –</p><p>S. enteritidis MIC:1.56 μg/mL –</p><p>P. aeruginosa MIC:6.25 μg/mL –</p><p>HSV-1: Herpes simplex virus type 1; EC50: 50% effective concentration; SI: selective index; HAE: hydroalcoholic extracts; A: relative to amphotericin B positive control;</p><p>B: relative to fluconazole positive control; C: relative to itraconazole positive control; D: methicillin-resistant S. aureus clinical strains; E: at maximum non-toxic</p><p>concentration; MIC: minimum inhibitory concentration; MBC: minimum bactericidal concentration; EO: essential oils.</p><p>A.P.A. Carvalho and C.A. Conte-Junior</p><p>Trends in Food Science & Technology 111 (2021) 534–548</p><p>539</p><p>isolated from leaf extract of this specie from Brazilian Cerrado biome</p><p>(Rodrigues et al., 2017). Still, the plasma antioxidant capacity of six</p><p>fruits from Brazilian Amazon, Cerrado, and Atlantic rainforest biomes</p><p>were reported with cagaita, cambuci, cupuaçu, garlic passion fruit,</p><p>Camu-Camu and jabuticaba juices increasing the oxygen radical absor-</p><p>bance capacity in plasma (measured by ORAC and FRAP assay) (Balis-</p><p>teiro et al., 2017).</p><p>The antioxidant capacity of Caryocar Brasiliense Camb. (known as</p><p>pequi or “souari nut”), a native specie from Brazilian Cerrado widely</p><p>used in local cooking, has been studied by several authors and has been</p><p>correlated with a variety of phytochemicals present in different parts of</p><p>pequi (e.g., pulp oil, leaves, and peel waste), analyzed by different</p><p>methods. Despite the significant content of phytochemicals of pequi</p><p>pulp oil is fatty acids (e.g., palmitic and linoleic acids) (Lima et al., 2007)</p><p>and the oil is soluble in non-polar solvents, as hexane and chloroform,</p><p>pulp oil also contain the antioxidants tocopherol and carotenoids (Car-</p><p>doso et al., 2013; Miranda-Vilela et al., 2014). Thus, the single extracted</p><p>of polyphenol from pequi pulp oil in polar methanol/ethanol presented,</p><p>by DPPH assay, and antioxidant activity of EC50 = 26 μg/mL, although it</p><p>was lower than BHT (EC50 = 0.0006 μg/mL) and ascorbic acid (EC50 =</p><p>0.012 μg/mL) positive controls (Roll et al., 2018). Compared to less</p><p>polar organic fractions of crude hydroalcoholic extract leaves (CHE),</p><p>Oliveira et al. (2018) found the highest total phenolic content (i.e.,</p><p>quercetin and gallic acids) and DPPH oxidation in more polar ethyl</p><p>acetate fraction (EAC) (4.0 mgGAE/mL, IC50 of 5.9 μg/mL) (p < 0.001)</p><p>than in less polar chloroform fraction (0.1 mgGAE/mL, IC50 of 76.4</p><p>μg/mL), athought EAC was lower that CHE (IC50 of 4.6 μg/mL) and</p><p>quercetin control (IC50 of 1.46 μg/mL) (T. S. de Oliveira et al., 2018). On</p><p>the other hand, the ethanolic extraction of pequi waste (peel) presented</p><p>high contents of total phenolic (3.77 mgGAE/mL), flavonoid (1.64</p><p>mgQE/mL), and anthocyanin (0.92 mgC3QEmL), as well as highly</p><p>effective as an antioxidant (90.44%) (p > 0.05) compared to BHT pos-</p><p>itive control (83.74%), after 120 min of analysis (Frasao et al., 2018).</p><p>The edible fruit of Pouteria glomerata, native from Brazilian Cerrado</p><p>and Pantanal (known as “laranjinha de pacu”) presented antioxidant</p><p>and nutritional capacity observed by its high levels of the vitamins,</p><p>minerals, insoluble dietary fiber, and malic acid, with better antioxidant</p><p>activity by DPPH of 6416 to 40,707 mmol.Trolox/100 g by aqueous</p><p>extracts of the freeze-dried peel and pulps (do Espirito Santo et al.,</p><p>2020). We also take the opportunity to highlight the nutritional power of</p><p>P. glomerata: since the content reported in freeze-dried (1549.08</p><p>mg/100 g) (do Espirito Santo et al., 2020) was four-time of fruits</p><p>considered rich source as vitamin C as orange (53.2 mg/100 g) (U.S.</p><p>Department of Agriculture, 2018), 30.2 g of fresh fruit or 4.4 g of</p><p>freeze-dried is enough to reach the average daily intake of vitamin C (i.</p><p>e., 65–70 mg/adults) as recommended by the Food and Nutrition Board</p><p>of the Institute of Medicine (Medicine & of, 2006). The antioxidant ac-</p><p>tivity of soluble fractions of pectic polysaccharides (rich in arabinoga-</p><p>lactans) extracted from agroindustrial co-products of Malpighia</p><p>emarginata (known as acerola), Anacardium occidentale (cashew apple),</p><p>Ananas comosus (pineapple), Mangifera indica (mango), and Passiflora</p><p>edulis (passion fruit) was also accessed, and the better result was IC50 of</p><p>147 μM found for cashew apple fruit co-products in comparison ascorbic</p><p>acid control (Bruno de Sousa Sabino et al., 2020). The aqueous fractions</p><p>of soluble dietary fibers of P. glomerata were also chemically charac-</p><p>terized and composed of monosaccharides of carbohydrates (e.g., uronic</p><p>acids, arabinose, and galactose) and heteropolysaccharides of pectic</p><p>nature (e.g., methyl-esterified homogalacturonans, arabinans, and ara-</p><p>binogalactans) (do Espirito Santo et al., 2020). These findings support</p><p>dietary fibers’ consumption, adding value to Brazilian foods and stim-</p><p>ulating their effects on consumers’ health improvement.</p><p>The Myrciaria jaboticaba (Vell.) O.Berg (known as “jabuticaba”) is a</p><p>Brazilian grape-like fruit native naturally occurring in Atlantic Forest,</p><p>with high sources of phenolic compounds in the peel and seeds with</p><p>great antioxidant capacity, genotoxicity to cancer cells and inhibition of</p><p>carbohydrates hydrolyzing enzymes (Alezandro et al., 2013; Fidelis</p><p>et al., 2021; Inada et al., 2015). The lyophilized jabuticaba seed extracts,</p><p>from M. jaboticaba was chemically characterized by Fidelis et al. (2021)</p><p>in terms of the total phenolic contents with values of 53,944 mg/100 g.</p><p>Of these, 39% was composed of castalagin, vescalagins, procyanidin A2,</p><p>gallic and ellagic acids and were correlated with antioxidant activity</p><p>measured by Folin-Ciocalteu, reducing the capacity of 31,338 mg.</p><p>GAE/100 g and metal ability chelating of 31,863 mg.EDTAE/100 g</p><p>(Fidelis et al., 2021).</p><p>Antimicrobial activity: Potentials to prevent certain infectious and</p><p>parasitic diseases.</p><p>The ethnopharmacological relevance of several plants of Brazilian</p><p>biomes, including an indigenous community of Rio das Cobras (Paraná</p><p>in southern), were addressed for several native species widely used for</p><p>indigenous and non-indigenous inhabitants to treatment several infec-</p><p>tious diseases.</p><p>Antiviral activity. Table 3 displayed the potential of some Brazilian</p><p>species with antiherpetic and antipoliovirus activity. A preliminary</p><p>study with Cordia americana and Ocimum gratissimum extract plants</p><p>demonstrated great inhibition hate and high selectivity to treat herpetic</p><p>infections and poliovirus, respectively (Moura-Costa et al., 2012).</p><p>However, the extract of the whole plant of O. gratissimum, rich in timol</p><p>and eugenol, showed better antiviral efficacy and selectivity against</p><p>poliovirus (de Toledo et al., 2011). Flavonoid-rich ethyl acetate fractions</p><p>of tarumã-do-Cerrado showed a virucide effect (in fruit extract) and</p><p>intracellular antiviral activity (in leaves extract) against</p><p>acyclovir-resistant herpes simplex virus type 1 (HSV-1) (Gonçalves</p><p>et al., 2001). Recently, the hydroalcoholic extracts of propolis from</p><p>Brazilian native bee showed the virucidal effect on HSV-1 without</p><p>cytotoxicity against fibroblast L929 cells line above 125 μg/mL, which</p><p>were attributed to a synergism of several bioactive compounds of its</p><p>complex composition (i.e., catechin, epicatechin, aromadendrin, nar-</p><p>ingenin, pinocembrin and p-coumaric acid) (Hochheim et al., 2019).</p><p>Antifungal activity. Table 3 addressed Brazilian native fruits and</p><p>plant species as potential candidates to develop novel drugs to treat</p><p>candidiasis and cryptococcosis diseases. Volatile oils obtained from</p><p>leaves of Brazilian endemic Eugenia dysenterica (Cagaita fruit), rich in</p><p>sesquiterpenes and monoterpenes, showed potent fungal inhibition ac-</p><p>tivity against Cryptococcus strains isolated from HIV-infected subjects</p><p>with cryptococcal meningitis, with MICs≥3.12 μg/mL to values up to</p><p>90% inhibition relative to reference fungicides against Cryptococcus</p><p>neoformans (T. R. Costa et al., 2000). Brazilian Cerrado species was also</p><p>studied against several species of Candida. The bark crude extract and</p><p>ethyl acetate fraction of C. americana were effective against Candida</p><p>albicans and Candida parapisilosis with low cytotoxicity to VERO cells</p><p>(CC50 = 307 μg/mL in Brazilian cachaça as extract liquor) and hence,</p><p>was suggested as a safe and effective candidate to be used in phytome-</p><p>dicine against fungal diseases (de Toledo et al., 2011). Coumarins and</p><p>alkaloids isolated from extracts of Pilocarpus pennatifolius collected in</p><p>the Rio Grande do Sul – Brazil exhibited great antifungal activity against</p><p>Candida spp., mainly for Jaborandine</p><p>and the not yet previously isolated</p><p>Penatifoline A against Candida krusei, which was better than fluconazole</p><p>reference fungicide (MIC: 3.12 μg/mL) (do Carmo et al., 2018). How-</p><p>ever, the hydroalcoholic extracts from bark and leaves of</p><p>S. terebinthifolius (the pink pepper or “aroeira”) and Campomanesia</p><p>eugenioides (Gabiroba), from indigenous reserve on Rio das Cobras</p><p>community, showed even more significant antifungal activity with a</p><p>highly selective index against Candida sp. (Moura-Costa et al., 2012)</p><p>Antibacterial activity. Table 3 summarizes some studies addressing</p><p>the antibacterial activity of Brazilian native food rich in bioactive</p><p>compounds. The potent antibacterial action of water extracts of Psidium</p><p>cattleianum (araçá or “strawberry guava”), rich in epicatechins, was</p><p>addressed by significant inhibition of Salmonella enteritidis proliferation</p><p>with MIC value of 5% (Medina et al., 2011). The babassu coconut</p><p>mesocarp extract is rich in phenolic acids, which was correlated with its</p><p>potent in vitro antibacterial activity against Enterococcus faecalis, Staph-</p><p>ylococcus aureus, and methicillin-resistant S. aureus (MRSA) and</p><p>A.P.A. Carvalho and C.A. Conte-Junior</p><p>Trends in Food Science & Technology 111 (2021) 534–548</p><p>540</p><p>antiseptic effect in vivo (Barroqueiro et al., 2016). The common path-</p><p>ways of antibacterial action of plant extracts rich in polyphenols have</p><p>been attributed to polyphenols’ capacity to react with the cell mem-</p><p>brane, inactivating essentials enzymes and impairing bacterial meta-</p><p>bolism (Coppo & Marchese, 2014; Cowan, 1999; Othman et al., 2019).</p><p>Recently, the not described yet coumarin (Xanthotoxin) and imidazole</p><p>alkaloid (Pennatifoline A) was isolated from Jaborandi leaves and barks</p><p>extracts and shown potent and twice strong antibacterial activity against</p><p>gram-negative Shigella flexneri, E. fecalis and S. enteritidis, compared to</p><p>antibacterial chloramphenicol (MI = 3.2 μg/mL) (do Carmo et al.,</p><p>2018). Most recently, the ethyl acetate fractions of Manihot esculenta</p><p>(cassava) leave extracts rich in polyphenol, saponin and quinone groups,</p><p>acted as antiacne herbal with the bactericidal effect against clinical</p><p>isolates of Propionibacterium acnes and Staphylococcus epidermidis (Mus-</p><p>tarichie et al., 2020). Taken together, these findings of Brazilian</p><p>endemic species illustrate and support the notion of the plant’s sec-</p><p>ondary metabolites, like polyphenols and alkaloids, can act as</p><p>resistance-modifying agents (Othman et al., 2019). Moreover, initial</p><p>evidence of antibacterial activity of the essential oils from flowers and</p><p>leaves of Eugenia klotzschiana (known as “pêra-do-cerrado”) by the</p><p>assessment of inhibition growth of gram-positive Streptococcus spp. and</p><p>gram-negative bacterium Prevotella nigrescens (Carneiro et al., 2017).</p><p>E. klotzschiana essential oils were rich in α-copaene (leave oil), β-bisa-</p><p>bolene (dry leave oil), and α-(E)-bergamotene (flowers oil).</p><p>Antiparasitic activity. Table 4 shows isolated compounds and ex-</p><p>tracts of Brazilian native plants with antiplasmodial, antileishmanial,</p><p>antischistosomal, and anti-echinococcus activities with suitable inhibi-</p><p>tion hates. Although its primary use as drug therapy for the echino-</p><p>coccosis parasitic diseases (hydatidosis) for inoperable patients,</p><p>benzimidazole carbamates, such as Albendazole (ABZ), are generally</p><p>toxic and has more parasitostatic rather than parasiticidal effectiveness</p><p>(Kern, 2010). In this context, Anarcadic acid (AA) from Brazilian cashew</p><p>nut shell liquid showed high potential as a novel drug for echinococcosis</p><p>due to high antiparasitic activity, by inhibiting angiogenesis: while has</p><p>negligible cytotoxicity against chang liver cells (IC50: 49 μM) and HepG2</p><p>cells (IC50: 70 μM), the higher in vitro AA efficacy on killing Echinococcus</p><p>granulosus s.s. Protoscoleces (MIC100%:20 μM after 24 h and MIC95%:0.5</p><p>μM after seven days) compared to 72 h treatment of Dihydroartemisinin</p><p>(DHA) (MIC100%: 40 μM) and ABZ treatment on day 7 (MIC56%:40 μM)</p><p>was reported (Yuan et al., 2019). Moreover, a better in vivo efficacy of</p><p>AA on inhibition growth and an in vitro efficacy on the damaged</p><p>germinal layer of Echinococcus multilocularis metacestodes were reported</p><p>higher than DHA- and ABZ-treated group (Yuan et al., 2019). Pre-</p><p>liminary studies with plants of an indigenous reserve in Rio das Cobras,</p><p>as Zanthoxylum rhoifolium and S. terebinthifolius, were also realized and</p><p>addressed its potential for antileishmanial treatment (Moura-Costa</p><p>et al., 2012). Similar findings were reported for Annona coriacea from</p><p>Cerrado against Leishmania amazonenses (de Toledo et al., 2011). Once</p><p>several Aspidosperma spp. are widely reported and used as medicinal</p><p>plants for the treatment of malaria, two species growth in Brazilian</p><p>Cerrado and Caatinga were also potential candidates with anti-</p><p>plasmodial activity without cytotoxicity on mammalian cell lines</p><p>(Ceravolo et al., 2018; M. L.; de Mesquita et al., 2007). The hexane</p><p>extract and the ethanolic extract from root barks of Matayba guianensis</p><p>and Aspidosperma macrocarpon, respectively, presented specific and</p><p>significant inhibition hates against a chloroquine-resistant strain of</p><p>Plasmodium falciparum, with the best selectivity index (MRC-5 cells) (M.</p><p>L. de Mesquita et al., 2007). Moreover, alkaloid solutions of leaves from</p><p>Brazilian Atlantic forest common known as “jaborandi” also presented</p><p>anthelmintic properties (Rocha et al., 2017). Overall, the alkaloid</p><p>pilocarpine isolated from Brazilian native Jaborandi is widely used for</p><p>glaucoma treatment (Pan, 2014), the most common blinding eye dis-</p><p>ease, and xerostomia treatment (Caldeira et al., 2017).</p><p>3.2. Potent anti-tumor activity for the prevention and treatment of cancer</p><p>Table 5 displays some Brazilian plant species’ overview as potential</p><p>candidates to develop novel drugs to treat cancer diseases, highlighting</p><p>fatty acids, polyphenols, diterpenes, and new drugs against human</p><p>breast, lung, colon, colorectal, brain, and skin cancer. Polyphenols are</p><p>compounds in Brazilian native food that has been related to several</p><p>chemoprevention modes of actions with high selectivity, without cyto-</p><p>toxicity to normal cells. In general, the high antioxidant capacity re-</p><p>ported for polyphenols has been related to the neutralization of</p><p>prooxidant-reactive molecules and activation of detoxified enzymes</p><p>expression, as catalase (CAT) and superoxide dismutase (SOD1)</p><p>(Colombo et al., 2015; dos Reis et al., 2020; Seraglio et al., 2018; Zhang</p><p>& Tsao, 2016). The studies overviewed in Table 5 provide evidence for</p><p>the usefulness of some native plants and fruits with in vitro anti-</p><p>proliferative activity against cancer cell lines and protection against in</p><p>vivo genotoxicity and oxidative stress in an experimental model of</p><p>cancer after fruit consumption.</p><p>The antiproliferative activity of polyphenols compounds (e.g., an-</p><p>thocyanins and ellagitannins) was verified against a non-androgen and</p><p>highly sensitive to diet influence the breast cancer cell, MDA-MB-231,</p><p>through nearly 60% inhibition on cell proliferation promoted by poly-</p><p>phenols metabolites in urinary excretion of women after a single dose of</p><p>Eugenia brasiliensis (known as grumixama) juice fruit intake (Teixeira</p><p>et al., 2017). The antiproliferative effect of P. cattleianum fruits extracts</p><p>on human breast cancer MCF-7 cells (49.7% of survivals) and colon</p><p>cancer Caco-2 cells (48.0% of survivals) in a dose-dependent manner</p><p>were also attributed to phenolic compounds, especially to epicatechins</p><p>and gallic acids present in the main content in the extracts (Medina</p><p>et al., 2011). In the case of proliferative inhibition of P. cattleianum ex-</p><p>tracts, the authors suggested a mechanism different from toxicity since</p><p>the survival rate of the control rat fibroblast</p><p>cells 3T3 was not affected</p><p>Table 4</p><p>Antiparasitic activity of natural bioactive compounds derived from Brazilian native plant species.</p><p>Specie Brazilian plant Form of plant part Parasite Doses Inhibition Ref.</p><p>A. coriacea Araticum Leaves (crude</p><p>extract)</p><p>Leishmania</p><p>amazonenses</p><p>1, 10, 100, 250, 500, and 1000</p><p>μg/mL</p><p>IC50 = 175 μg/mL de Toledo et al. (2011)</p><p>A. macrocarpon Peroba Root bark (extract) Plasmodium</p><p>falciparum</p><p>10 μg/mL IC50 = 4.9 μg/mL,</p><p>SI:16.4</p><p>(M. L. de Mesquita et al.,</p><p>2007)</p><p>A. occidentale Cashew nutshell CNSL (Anarcadic</p><p>acid)</p><p>Echinococcus</p><p>granulosus</p><p>MIC: 0.5 μM on day 7 92.5% Yuan et al. (2019)</p><p>M. guianensis Camboatá-</p><p>Branco</p><p>Root bark (extract) Plasmodium</p><p>falciparum</p><p>10 μg/mL IC50 = 6.1 μg/mL,</p><p>SI:16.4</p><p>(M. L. de Mesquita et al.,</p><p>2007)</p><p>P. microphyllus Jaborandi Leaves (alkaloids) Schistosoma mansoni 3.125 μg/mL 100% Rocha et al. (2017)</p><p>S. terebinthifolius Pink pepper Barks (aqueous</p><p>extracts)</p><p>Leishmania</p><p>amazonensis</p><p>– IC50 = 201 μg/mL Moura-Costa et al. (2012)</p><p>Z. rhoifolium "Mamica de</p><p>cadela"</p><p>Leaves (50% HAE) Leishmania</p><p>amazonensis</p><p>– IC50 = 143 μg/mL Moura-Costa et al. (2012)</p><p>IC50: 50% inhibition of parasite growth; SI: selectivity index for mammalian cell line MRC-5; HAE: hydroalcoholic extracts; MIC: minimum inhibitory concentration;</p><p>CNSL: Brazilian cashew-nut shell liquid.</p><p>A.P.A. Carvalho and C.A. Conte-Junior</p><p>Trends in Food Science & Technology 111 (2021) 534–548</p><p>541</p><p>by the treatment extract. Also, aqueous leaf extract fractions of Stryph-</p><p>nodendron adstringens (popularly known as Barbatimão), rich in proan-</p><p>thocyanidins (e.g., gallic acid, catechin and epicatechin), significantly</p><p>decreased cell viability for two human breast cancer cells, MCF-7 (IC50</p><p>= 15.34 μg/mL) and MDA-MB-435 (IC50 = 69.95 μg/mL), without</p><p>cytotoxicity to normal cell lines (IC50 = 14,453.11 μg/mL) (Sabino et al.,</p><p>2018, pp. 1375–1389). Most recently, Fidelis et al. (2021) reported the</p><p>antiproliferative effect of lyophilized jabuticaba seed extracts (LJE)</p><p>decreasing the cell viability of three colon cancer cell lines Caco-2 (IC50</p><p>= 451.4 μg/mL), A549 (IC50 = 374.4 μg/mL), and HepG2 (IC50 = 433.5</p><p>μg/Ml) without cytotoxicity to normal cells IMR90 (IC50 > 2000</p><p>μg/mL). The authors explain the results were linking the antioxidant</p><p>effect in normal cells while prooxidant action and ROS increasing in</p><p>A549 cells caused by polyphenols (e.g., castalagin, vescalagins, pro-</p><p>cyanidin A2, and ellagic acid) present in main contents in LJE. Probably,</p><p>the high content of ions copper naturally present in cancer cells could</p><p>interact with polyphenols in a Fenton-type reaction, generating the OH</p><p>radical, might causing DNA damage and apoptosis (Eghbaliferiz &</p><p>Iranshahi, 2016; Fidelis et al., 2021). Furthermore, LJE incorporated</p><p>into a yogurt model to treat rats-bearing colorectal cancer exerts a</p><p>prebiotic effect by modulating gut microbiota (Fidelis et al., 2021).</p><p>Dietary supplementation with antioxidant rich-phenolic compounds</p><p>(e.g., anthocyanins) of Brazilian native foods was reported as a protec-</p><p>tive factor against the development of in vivo experimental model of</p><p>Table 5</p><p>In vitro antiproliferative activity and in vivo anti-tumor effects of Brazilian native natural compounds fruits and plants.</p><p>In vitro antiproliferative activity</p><p>Specie Brazilian fruit/</p><p>plant</p><p>Form product Bioactive compounds Cell lines Antiproliferative effect Ref.</p><p>A. angustifolia Paraná pine Lyophilized powder from</p><p>bracts extracts</p><p>Catechin, epicatechin,</p><p>quercetin, and apigenin</p><p>Lung fibroblasts MRC5 25–50 μg/mL* (M. Souza et al.,</p><p>2014)</p><p>A. angustifolia Paraná pine Lyophilized bracts extract Flavonoids and tannins Laryngeal carcinoma</p><p>HEp-2</p><p>80% after 250 μg/mL Branco et al. (2015)</p><p>C. langsdorffi Copaiba Oil (NCCimq) Copalic acid Human keratinocytes</p><p>(HaCaT);</p><p>Pig abdominal skin</p><p>– Venturini et al.</p><p>(2015)</p><p>C. langsdorffi Copaiba Oleoresin (isolated</p><p>compounds)</p><p>Copalic acid Human breast cancer</p><p>(MCF-7)</p><p>IC50 = 488.90 μg/mL Abrão et al. (2015)</p><p>Hamster lung cancer</p><p>(V79)</p><p>IC50 = 365.90 μg/mL</p><p>C. sylvestris Guaçatonga Stem bark hexane extract Triterpene lactone:</p><p>glaucarubinone</p><p>Human colon</p><p>carcinoma HCT-8</p><p>0.1 μg/mL (Mariana Laundry</p><p>de Mesquita et al.,</p><p>2009) Melanoma MDA-MB-</p><p>435</p><p>1.2 μg/mL</p><p>Brain SF-295 0.9 μg/mL</p><p>Leukemia HL-60 1.3 μg/mL</p><p>E. brasiliensis Grumixama/</p><p>Brazilian cherry</p><p>Urinary polyphenol</p><p>metabolites in women after</p><p>GJ intake</p><p>Anthocyanins Ellagitannins Breast cancer cells</p><p>(MDA-MB-231)</p><p>~ 60% of cell</p><p>proliferation inhibition</p><p>Teixeira et al.</p><p>(2017)</p><p>M. jaboticaba Jabuticaba Lyophilized jabuticaba seed</p><p>extract</p><p>Castalagin, vescalagins,</p><p>procyanidin A2, and ellagic</p><p>acid</p><p>Colon cancer Caco-2</p><p>cells</p><p>IC50 = 451.4 μg/mL Fidelis et al. (2021)</p><p>Colon cancer A549</p><p>cells</p><p>IC50 = 451.4 μg/mL</p><p>Colon cancer HepG2</p><p>cells</p><p>IC50 = 451.4 μg/mL</p><p>Normal IMR90 IC50 > 2000 μg/mL</p><p>P. cattleianum Araçá 80 μg/mL of fruit extracts Epicatechins and gallic acids Breast cancer</p><p>MCF-7 cells</p><p>49.7% of survival Medina et al.</p><p>(2011)</p><p>Colon cancer Caco-2</p><p>cells</p><p>48% of survival</p><p>S. adstringens Barbatimão Leafs (aqueous fractions) Proanthocyanidins Breast cancer cells</p><p>MCF-7/MDA-MB-435</p><p>IC50 = 15.34 μg/mL/</p><p>IC50: 69.95 μg/mL</p><p>Sabino et al. (2018)</p><p>S. versicolor Pau-paraíba Root bark ethanol extract Triterpene lactone:</p><p>glaucarubinone</p><p>Human colon</p><p>carcinoma HCT-8</p><p>0.5 μg/mL (Mariana Laundry</p><p>de Mesquita et al.,</p><p>2009) Melanoma MDA-MB-</p><p>435</p><p>1.5 μg/mL</p><p>Brain SF-295 0.7 μg/mL</p><p>Leukemia HL-60 1.1 μg/mL</p><p>T. grandiflorum Cupuaçu Seed butter (NBLimq) Palmitic and linoleic acids Human keratinocytes</p><p>(HaCaT);</p><p>Pig abdominal skin</p><p>– Venturini et al.</p><p>(2015)</p><p>In vivo anti-tumor effects</p><p>Specie Brazilian fruit Treatment Living organism Experimental cancer</p><p>model</p><p>In vivo outcome Ref.</p><p>C. brasiliense Pequi Oil or extract</p><p>supplementation (15 mL, 60</p><p>days)</p><p>Male mice (BALB/C, n = 40,</p><p>8–12 weeks old)</p><p>Urethane-induced lung</p><p>cancer</p><p>↓ oxidative stress</p><p>↓ genotoxicity</p><p>Colombo et al.</p><p>(2015)</p><p>E. edulis Juçara Fruit pulp supplementation Rattus norvegicus strains (165</p><p>days old)</p><p>Urethane-induced</p><p>colorectal</p><p>carcinogenesis</p><p>↓ ACF, ACF>3 crypt,</p><p>↑ SOD1 expression</p><p>dos Reis et al.</p><p>(2020)</p><p>M. jaboticaba Jabuticaba Jabuticaba yogurts feed Male Wistar rats (7 weeks</p><p>old)</p><p>Hydrazine-induced</p><p>colon cancer</p><p>Modulation of gut</p><p>microbiota</p><p>Fidelis et al. (2021)</p><p>GJ: grumixama juice; ACF: aberrant crypt foci; SOD1: superoxide dismutase 1 gene; *concentration to minimize and altogether avoid (900 μM) H2O2-induced</p><p>mortality; ↓: reduction; ↑: increasing.</p><p>A.P.A. Carvalho and C.A. Conte-Junior</p><p>Trends in Food Science & Technology 111 (2021) 534–548</p><p>542</p><p>hydrazine and urethane-induced colorectal carcinogenesis through di-</p><p>etary intake with Euterpe edulis (juçara) pulp fruit, and M. jaboticaba</p><p>(jaboticaba) seed yogurt, by a reduction in the number of aberrant crypt</p><p>foci (ACF), SOD1 gene expression in the colorectal mucosa (dos Reis</p><p>et al., 2020), and regulation of the gut microbiota, respectively (Fidelis</p><p>et al., 2021). Similarly, native oil from Brazilian Cerrado rich in carot-</p><p>enoids: C. brasiliense (pequi) oil/extract supplementation was related to</p><p>lipid peroxidation modulation, thus reducing the DNA damage by</p><p>oxidative stress of urethane-induced lung carcinogenesis (Colombo</p><p>et al., 2015). Based on evidence reported, the juçara pulp fruit, jaboti-</p><p>caba seeds, and pequi oil were suggested as high potential candidates for</p><p>dietary supplementation and the development of novel drugs to prevent</p><p>and treat colorectal, colon, and lung cancer, respectively.</p><p>Abrão et al. (2015) pointed out the potential of the amazon Copaifera</p><p>langsdorffi (copaiba) oleoresin and its isolated compounds to develop</p><p>anti-cancer drugs and suggested that its isolated diterpenes, as copalic</p><p>acid, might be associated with the antiproliferative reported against</p><p>Chinese hamster lung fibroblasts (V79) (IC50: 365.90 μg/mL), and</p><p>human breast adenocarcinoma (MCF-7) (IC50: 488.90 μg/mL) cell lines</p><p>without cytotoxicity to normal cells (Abrão et al., 2015). Furthermore,</p><p>the authors associated the mechanism of actions with apoptotic cell</p><p>death. Likewise, Mesquita et al. (2009) addressed several Brazilian</p><p>Cerrado plants’ cytotoxic activity, rich in phytochemical triterpene</p><p>lactone (i.e., glaucarubinone) used in traditional medicine against four</p><p>different cancer cell lines. A stronger activity was found for the hexane</p><p>extract of Casearia sylvestris (known as “guaçatonga”) stem bark and</p><p>ethanol extract of Simarouba versicolor (popularly known as</p><p>“pau-paraíba”) root bark on human colon carcinoma HCT-8 (IC50 =</p><p>0.1–0.5 μg/mL), melanoma MDA-MB-435 (IC50 = 1.2–1.5 μg/mL), brain</p><p>tumor SF-295 (IC50 = 0.7–0.9 μg/mL), and leukemia HL-60 (IC50 =</p><p>1.1–1.3 μg/mL) cells (Mariana Laundry de Mesquita et al., 2009).</p><p>Nanocapsules of amazon copaiba oil (NCCimq), from C. langsdorffi,</p><p>with antiproliferative properties and nanostructured Brazilian solid</p><p>lipid, obtained from Theobroma grandiflorum (cupuaçu, a tree related to</p><p>cacao) seed butter, (NBLimq), rich in linoleic and palmitic acids were</p><p>employed to encapsulate imiquimod-loaded nanocarriers in tumor cell</p><p>lines, promising to treat skin carcinoma beyond a cutaneous direct</p><p>nanostructured system with biocompatible with human skin cells and</p><p>suitable physical-chemical features (Venturini et al., 2015).</p><p>C. langsdorffi nanocapsules were the most promissive system due to the</p><p>significant controlled drug delivery in a synthetic membrane (100% of</p><p>drug release after 600 min in comparison to 180 min for free drug</p><p>control); copaiba oil shows increased drug retention in the skin layers in</p><p>vitro skin penetration/permeation in a membrane of female porcine skin</p><p>cells abdomen (the content of imiquimod retained in the dermis of</p><p>NCCimq were 77% against 46% for NBLimq) (Venturini et al., 2015). The</p><p>controlled drug release might be due to interactions with the linoleic and</p><p>palmitic acids from Brazilian lipids with imiquimod. These results</p><p>further support the idea of natural nanostructured lipid carriers could be</p><p>applied to modulate the penetration/permeation of active substances in</p><p>the skin through the control of the rate of release of the irritative drugs</p><p>(e.g., imiquimod) (Micali et al., 2010) in contact with the outermost</p><p>layer of the epidermis, reducing the skin reactions (Castro et al., 2009)</p><p>and hence, highly promising for treat skin cancer (Jain et al., 2020).</p><p>Fig. 1. Antioxidants-rich food/plants native in Brazil, cell redox balance and oxidative stress: in vitro and in vivo antiproliferative effects after fruit treatment.</p><p>A.P.A. Carvalho and C.A. Conte-Junior</p><p>Trends in Food Science & Technology 111 (2021) 534–548</p><p>543</p><p>The A. angustifolia bract extract (AAE) rich in flavonoids and tannins</p><p>also presented a selective killing of cancer cells by a strong cytotoxic</p><p>effect against Larynx carcinoma HEp-2 cells (after 72 h and 250 μg/mL</p><p>AAE treatment, the cytotoxic rate was 80%) with more vulnerability</p><p>than normal epithelial cell lines HEK-293, that might be associated with</p><p>an inhibition effect of polyphenols on mitochondrial ETC complexes,</p><p>causing improvement on intracellular ROS generation and following</p><p>apoptosis (Branco et al., 2015). The antigenotoxic effect of</p><p>polyphenols-rich extracts of natural wastes bracts Brazilian pine tree</p><p>A. angustifolia in human lung fibroblast cells was verified by its antiox-</p><p>idant enzyme-like action against 900 μM H2O2-induced mortality and</p><p>oxidative damage of lipids, proteins, and DNA in human lung fibroblast</p><p>cells (MRC5) (M. Souza et al., 2014). Thus, these findings illustrate how</p><p>waste bracts, a non-edible part of Brazilian native flora used in tradi-</p><p>tional medicine, can play an essential role in the inhibition of oxidative</p><p>mechanisms associated with carcinogenesis and degenerative diseases</p><p>due to its scavenges capacity and potent SOD and CAT -like activities</p><p>promoted by phenolic compounds. Fig. 1 shows antioxidants-rich</p><p>food/plants native in Brazil, cell redox balance and oxidative stress</p><p>connected through in vitro and in vivo antiproliferative effects after fruit</p><p>treatment.</p><p>Table 6</p><p>Brazilian native foods as a source of natural bioactive compounds with anti-diabetic, anti-obesity, nutritional and endocrine effects: in vitro, in vivo, and clinical trials.</p><p>Specie Brazilian</p><p>fruit/plant</p><p>Bioactive compounds Intervention Model/Participants Outcome Ref.</p><p>A. speciosa Babassu</p><p>(mesocarp)</p><p>Carbohydrates,</p><p>saponins, flavonoids,</p><p>and tannins</p><p>Feed intake during RT:</p><p>BAE (25 mg/kg), 5</p><p>times/week.</p><p>In vivo: Male Swiss</p><p>mice, 60 days old,</p><p>35–60 g</p><p>Immunomodulation of lymphocytes and</p><p>macrophages; cytokine production; ↓ LDL</p><p>and TG levels</p><p>Soares et al.</p><p>(2020)</p><p>B. excelsa Brazil nut vitamin E, and phenolics</p><p>(gallic</p><p>and ellagic acid)</p><p>9.42 g/day intake</p><p>during 11 weeks</p><p>Meta-analysis: 315</p><p>participants</p><p>↑ Plasma selenium levels ↑ GPx levels Li et al. (2020)</p><p>E. edulis Juçara Dietary fiber, fatty acids,</p><p>and anthocyanins</p><p>Freeze-dried pulp</p><p>intake</p><p>Obese adults ↑ Serum fatty acids profile. ↑ epigenetic</p><p>markers in monocytes</p><p>Santamarina</p><p>et al. (2018)</p><p>E. edulis Juçara Dietary fiber, fatty acids,</p><p>and anthocyanins</p><p>0.5–0.25% freeze-dried</p><p>pulp intake</p><p>Male Wistar rats Prevention of peripheral inflammation,</p><p>body weight gain, and liver injury</p><p>Santamarina</p><p>et al. (2019)</p><p>E. uvaia Uvaia Phenolics Juice-HFD group intake</p><p>(2 mL/day, 8 weeks)</p><p>Female Fischer rats</p><p>(7-week-old)</p><p>↑ Glutathione levels ↑ CAT activities</p><p>↓ PCO levels</p><p>Lopes et al.</p><p>(2018)</p><p>C. phaea Cambuci Ellagic acid, syringic</p><p>acid</p><p>Juices (polyphenol-rich</p><p>extracts)</p><p>In vitro α-GLU 1.1 μg CE/mL Balisteiro et al.</p><p>(2017) C. phaea Cambuci In vitro α-AMY 0.49 μg CE/mL</p><p>C. phaea Cambuci Phenolics 300 mL clarified juice Healthy individuals-</p><p>50 g of white bread</p><p>intake</p><p>↓ Serum glucose levels</p><p>↓ Postprandial glycemia</p><p>Balisteiro et al.</p><p>(2017)</p><p>E. dysenterica Cagaita Terpenes, flavonoids,</p><p>and phenols</p><p>Plants (water crude</p><p>extract)</p><p>In vitro α-GLU IC50: 0.5 μg/mL (P. de Souza</p><p>et al., 2012) In vitro α-AMY IC50:14.9 μg/mL</p><p>E. dysenterica Cagaita Ellagic acid, syringic</p><p>acid</p><p>Juice (polyphenol-rich</p><p>extracts)</p><p>In vitro α-GLU 1.0 μg CE/mL Balisteiro et al.</p><p>(2017) In vitro α-AMY 0.21 μg CE/mL</p><p>E. dysenterica Cagaita Phenolics Clarified juice (300 mL) Healthy individuals-</p><p>50 g of white bread</p><p>intake</p><p>↓ Serum glucose levels</p><p>↓ Postprandial glycemia</p><p>Balisteiro et al.</p><p>(2017)</p><p>P. caimito Abiu Terpenes, flavonoids,</p><p>and phenols</p><p>Plants (water crude</p><p>extract)</p><p>In vitro α-GLU IC50:2.6 μg/mL (P. de Souza</p><p>et al., 2012) In vitro α-AMY IC50:13.1 μg/mL</p><p>P. ramiflora Curriola Terpenes, flavonoids,</p><p>and phenols</p><p>Plants (water crude</p><p>extract)</p><p>In vitro α-GLU IC50:0.3 μg/mL (P. de Souza</p><p>et al., 2012) In vitro α-AMY IC50: 7.1 μg/mL</p><p>P. ramiflora Curriola Tannins and flavonoids Stem and root barks</p><p>(extracts)</p><p>In vitro α-AMY (HSA) 95–100% at a final concentration of 20</p><p>μg/mL</p><p>de Gouveia et al.</p><p>(2013)</p><p>P. ramiflora Curriola Tannins and flavonoids 25, 50 and 100 mg/kg</p><p>PrSBAE intake (8 days)</p><p>Salivary α-AMY in</p><p>adult male Swiss</p><p>mice</p><p>↓ Blood glucose levels ↓ Bodyweight de Gouveia et al.</p><p>(2013)</p><p>P. ramiflora Curriola Friedelin, Epi-</p><p>friedelanol, Taraxerol</p><p>Leaves (EBH, F1 and</p><p>F2) (1 mg/mL)</p><p>In vitro α-AMY EBH: ~50%</p><p>F1: ~75%</p><p>F2: ~85%</p><p>Rodrigues et al.</p><p>(2017)</p><p>P. ramiflora Curriola</p><p>Sesquiterpenes</p><p>Monoterpenes</p><p>Lyophilized aqueous</p><p>extract intake (500 mg/</p><p>kg bw)</p><p>Diabetic-induced</p><p>rats</p><p>↓ Blood glucose levels</p><p>↓ Bodyweight</p><p>↓ diabetic nerve damage</p><p>(A. V. da Costa</p><p>et al., 2013)</p><p>P. torta Abiu Terpenes, flavonoids,</p><p>and phenols</p><p>Plants (water crude</p><p>extract)</p><p>In vitro α-GLU (iv) IC50:0.2 μg/mL (P. de Souza</p><p>et al., 2012) In vitro α-AMY (iv) IC50: 5.7 μg/mL</p><p>Phenolics and</p><p>flavonoids</p><p>Epicarp (crude</p><p>extraction)</p><p>In vitro α-AMY 92%, IC50 = 73.6 μg/mL de Sales et al.</p><p>(2017)</p><p>M. jaboticaba Jabuticaba Polyphenols LJE extracts/yogurt</p><p>(0.4 g/100 g)</p><p>In vitro α-AMY ~40% Fidelis et al.</p><p>(2021) In vitro α-GLU ~45%</p><p>In vitro ACE-I ~63%</p><p>S. adstringens Barbatimão Tannins, alkaloids,</p><p>flavonoids, and steroids</p><p>Cream with 6.0% of</p><p>bark extract</p><p>Subjects with an</p><p>excess of terminal</p><p>hair</p><p>Suppression of terminal hair growth. ↓</p><p>Terminal hair. ↓ skin hyperpigmentation,</p><p>folliculitis and acne</p><p>Vicente et al.</p><p>(2009)</p><p>T. grandiflorum Cupuaçu Polyphenols and</p><p>theograndins</p><p>1 mL/day intake of EC</p><p>(1 g/mL) during 8</p><p>weeks</p><p>In vivo: Male adult</p><p>Wistar rats</p><p>↓ Feed intake, ROS and NO levels, 3-NT,</p><p>Interleukin-6, and eNOS.</p><p>Punaro et al.</p><p>(2019)</p><p>α-AMY: α-amylase inhibition assay; α-GLU: α-glucosidase inhibition assay; HAS: human salivary α-amylase; BAE: babassu mesocarp extract; CE: catechins equivalents;</p><p>EBH: crude hexane extract; F1: hexane; F2: hexane/ethyl acetate fraction; IC50: 50% inhibitory concentration; PrSBAE: stem bark aqueous extract of P. ramiflora; n/f:</p><p>no effect; ↓: reduction; ↑: increasing; GPx: glutathione peroxidase; T3: triiodothyronine hormone; TSH: Thyroid-stimulating hormone. ROS: reactive oxygen species;</p><p>NO: nitric oxide; 3-NT: 3-nitrotyrosine; eNOS: endothelial nitric oxide synthase; MiMC: Mouse immortalized mesangial cells; EC: extract of frozen pulp cupuaçu; BAE:</p><p>aqueous babassu mesocarp extract; RT: resistance training; LJE: lyophilized jabuticaba seeds; ACE-I: Angiotensin-converting-enzyme inhibitors.</p><p>A.P.A. Carvalho and C.A. Conte-Junior</p><p>Trends in Food Science & Technology 111 (2021) 534–548</p><p>544</p><p>3.3. Anti-diabetic, anti-obesity, nutritional and other endocrine/</p><p>metabolic effects</p><p>Active secondary metabolites from Brazilian native foods and their</p><p>potential to control the metabolic syndrome diseases factors related to</p><p>obesity, diabetes and its associated complications, hypertension, DM</p><p>and CVD risks, epigenetic markers, immune- and inflammatory modu-</p><p>lations, and other endocrine/metabolic effects through in vitro, in vivo</p><p>and clinical trials, were reviewed and summarized in Table 6. The</p><p>studies generally target both enzymatic and non-enzymatic oxidative</p><p>stress: DNA damage, nitrosative/oxidative stress, carbohydrates diges-</p><p>tive enzymes, angiotensin-converting enzymes, and steroid metabolism</p><p>enzymes, and other factors. We can observe that studies summarized</p><p>following previous studies reported the capacity of carbohydrates</p><p>digestion enzymes inhibition by plant extracts is generally attributed to</p><p>polar phytochemicals, as phenolic, tannins, and triterpenoid</p><p>compounds.</p><p>Earlier observations of Souza et al. (2012) showed that P. torta leaves</p><p>aqueous crude extract strong inhibited the in vitro α-amylase and</p><p>α-glucosidase activities with IC50 values of 0.2 μg/mL and 5.7 μg/mL,</p><p>respectively. Notwithstanding, P. torta epicarp crude ethanol extract</p><p>(PTE) and ethyl acetate fraction (III) are rich in phenolics and flavonoids</p><p>and inhibited in vitro α-amylase activity more than pulp fruit: 92% of</p><p>inhibition with an IC50 of 73.6 μg/mL (in PTE) and 85% of inhibition</p><p>with an IC50 of 79.1 μg/mL (in III) (de Sales et al., 2017). However,</p><p>authors highlighted a non-correlation between antioxidant capacity,</p><p>α-amylase inhibition and phytochemicals in P.torta since fraction III</p><p>presented higher values of antioxidant, yield, total phenolic and flavo-</p><p>noid contents (yield: 89% referred to PTE; TPC: 252.10 μgGAE/mg;</p><p>TFC:19.30 μgQE/mg) compared to PTE (yield: 4% referred to plant</p><p>material; TPC: 125.25 μgGAE/mg; TFC:0.14 μgQE/mg) (de Sales et al.,</p><p>2017). On the other hand, other research have concluded that tri-</p><p>terpenoids, in addition to phenolics, flavonoids and tannins, also can be</p><p>responsible for the outstanding values of in vitro α-amylase inhibition</p><p>found for Pouteria spp. extracts. The first time isolation of the triterpene</p><p>friedelin from Pouteria genus in combination with identification of</p><p>epi-friedelanol was associated with potent in vitro α-amylase inhibition</p><p>of ~50% in hexane crude extracts (EBH) and ~85% in hexane-ethyl</p><p>acetate fractions (F2), respectively, of P. ramiflora leaves (Rodrigues</p><p>et al., 2017). The highest activity of F2 was correlated with the highest</p><p>content of epi-friedelanol in this more polar fraction. This study clarifies</p><p>and complements Gouveia et al. (2013) earlier observations, which</p><p>showed that hexane extract (stem bark) and ethanolic extract (root</p><p>barks) of P. ramiflora, at a final concentration of 20 μg/mL, inhibited</p><p>human salivary α-amylase activity from 95 to 100%, suggesting a cor-</p><p>relation with polar compounds as flavonoids retrieved for hexane</p><p>extract (stem bark) and tannins for ethanolic extract (root barks).</p><p>Moreover, other Brazilian Cerrado species-rich in terpenes, flavo-</p><p>noids, and phenolics, especially P. ramiflora and P. torta, also showed</p><p>great values of IC50 by inhibition of in vitro α-amylase (of 7.1 and 5.7 μg/</p><p>mL) and α-glucosidase (0.3 and 0.2 μg/mL) (P. de Souza et al., 2012).</p><p>Increased IC50 values of in vitro α-glucosidase and α-amylase inhibition</p><p>of polyphenol-rich extracts of E. dysenterica (α-AMY: 0.21 μg CE/mL and</p><p>α-GLU:1.0 μg CE/mL) and C. phaea (α-AMY: 0.49 μg CE/mL and</p><p>α-GLU:1.1 μg CE/mL) corroborates these earlier findings for Cerrado</p><p>species (Balisteiro et al., 2017). More recently, extracts or yogurt of</p><p>polyphenol-rich LJE showed in vitro inhibition of the α-amylase,</p><p>α-glucosidase and angiotensin-converting enzymes 1 (ACE-I) (Fidelis</p><p>et al., 2021).</p><p>Despite the anti-diabetic effects of phytochemicals derived from</p><p>Pouteria sp. discussed above, another essential finding provides pieces of</p><p>evidence that Brazilian cerrado fruits have the potential to reduce the</p><p>type 2 diabetes risk: in comparison with water, 300 mL of clarified juice</p><p>from E. dysenterica and C. phaea fruits intake were highlighted in</p><p>reduction of postprandial glycemia and serum glucose levels in healthy</p><p>individuals after consumption of carbohydrate meal (Balisteiro et al.,</p><p>2017).</p><p>Recently, an in vivo study reported the daily intake of aqueous frozen</p><p>pulp extract of cupuaçu (cacao-like fruit from Amazon biome), rich in</p><p>theograndin I, reduced nitrosative stress in a diabetic kidney model and</p><p>modulated inflammatory factors reducing the levels of ROS, nitric oxide</p><p>(NO), Neurotrophin-3 (3-NT), interleukine-6, 3-nitrotyrosine and</p><p>endothelial nitric oxide synthase (Punaro et al., 2019). Moreover, the</p><p>cupuaçu extract was no cytotoxic to mouse immortalized mesangial cells</p><p>(MiMC) at doses of 500, 100, 50 or 10 mg/mL during 24, 48 or 72 h of</p><p>analysis, and reduced the levels of NO and ROS in high glucose medium</p><p>(Punaro et al., 2019). This finding is consistent with that of Gouveia</p><p>et al. (2013) and Costa et al. (2013), who found a reduction in body</p><p>weight and glycemia levels after the treatment of rats-induced diabetes</p><p>with stem bark aqueous extract and lyophilized aqueous extract (plants)</p><p>of P. ramiflora, respectively. Additionally, the P. ramiflora extract pro-</p><p>vided a neuroprotective effect against oxidative damage and myosin-Va</p><p>expression in the brain, preventing impairment of hippocampal func-</p><p>tions (A. V. da Costa et al., 2013). These finds are particularly relevant to</p><p>insights into delay the onset of diabetic complications, once hypergly-</p><p>cemia and oxidative/nitrosative</p>