Antioxidant property of secondary metabolites from Garcinia genus: A short review

The increase in consumption of ultra-processed foods and other modern habits harmful to health contribute to the growth in the number of people with chronic diseases such as diabetes, hypertension and obesity (Almarshad et al., 2022). This situation leads to the requirement of research for alternatives in the treatment of these problems. Due to low cost and low side effects, natural products that have health benefits are the target of studies in order to develop remedies that act in this type of disease (A. Onaolapo and O. Onaolapo, 2020).

Species of the Garcinia genus (Clusiaceae family) are a relevant source of bioactive compounds. They are used in traditional medicine against problems frequently associated to oxidative stress, such as chronic ulcers, dysentery, diarrhea, gonorrhea, and diabetes (Aizat et al., 2019a; Mello et al., 2021). Approximately 450 species belong to this genus, and they are commonly found as trees, shrubs or subshrubs, occurring in Asia and some countries in Africa and South America (Mohamed and Ibrahim, 2020). A common feature among species of this genus is the production of yellow sap, occasionally white, in the endocarp of the fruit, bark and wood (Aizat et al., 2019b; Inoue et al., 2017; Machado et al., 2017).

Several biological activities have been described for Garcinia species, including anticancer, anti-inflammatory, antimicrobial, antiviral, antidepressant, antioxidant, and neuroprotective activity against Alzheimer’s disease. In addition, the antiobesity activity and appetite suppressant activity has been commercially explored through many supplements based on extracts of Garcinia spp. (Pandey et al., 2017). This relevant and diversified biological potential is attributed to the xanthones and benzophenones, the most abundant classes of metabolites found in these plants (Do and Cho, 2020; Inoue et al., 2017; Kurniawan et al., 2021; Mello et al., 2021; Wairata et al., 2022; Wang et al., 2017; Zafar et al., 2019).

Garcinia mangostana, the most studied species, is popularly known as mangosteen. It is cultivated for its peculiar bittersweet taste and it is also known as the queen of fruits due to its sweet-sour taste and the wide range of medicinal benefits (Aizat et al., 2019a). In traditional medicine, the pericarp of this species has been used to treat inflammation, ulcer, skin infection, amoebic dysentery, wound healing, and diarrhea (Wang et al., 2017). G. cochinchinensis is similar in phenotype to G. mangostana and is called yellow mangosteen or false mangosteen, depending on the region of occurrence. In the young fruit stage, the G. cochinchinensisis confused with G. mangostana; the latter being typical of Southeast Asian countries such as Malaysia, Indonesia, Thailand and China. The tropical tree of G. mangostana can reach up to 25 m in height. The fruit in its mature stage is purple. In popular medicine, the pericarp has been used to treat inflammation, ulcer, and skin infection. In addition, several parts of G. mangostana are prepared by dissolving in water and after the fruit extract is commercialized as functional food and drink (Aizat et al., 2019b; Wang et al., 2017). G. xanthochymus is a perennial medium-size tree that can reach up to 20 m height and it is distributed in China, South East Asia and Western Gates of India. The G. xanthochymusfruit has a sub globose form, turns yellow when it is mature, and the seeds are embedded in yellow pulp. The fruits are eaten fresh or processed to make jams, vinegar, beverages and other food products. As well as other species of this genus, various subparts of the plant are used in the research like barks, leaves, seeds, stem bark and others (Hassan et al., 2018; Prakash et al., 2022).

In American countries there are some Garcinia species such as G. brasiliensisand G. gardneriana, which are used to treat inflammation, pain and urinary infections. These species are native to the Amazonian region; G. brasiliensis, for example is known as bacuri, bacupari or bacuripari. The fruit of G. brasiliensis is yellow and has a sour-sweet pulp. It has also anti-inflammatory, antinociceptive, antitumoral and antioxidant properties (Demenciano et al., 2020; Espirito Santo et al., 2020).

Species like G. atroviridis, G. cola, G. cambogia and G. indica are used to treat degenerative diseases, such as obesity, diabetes mellitus, and arthritis, as well as other metabolic syndromes (Kuswandi et al., 2022). G. cambogia is used as an antiobesity supplement and can be effective in terms of weight loss (Andueza et al., 2021; Han et al., 2021). Andueza et al., (2021) warn about the negative effect of Garcinia supplements for weight loss because it can be associated with liver damage and to lesser extent with serotonin toxicity.

The responsible compounds by antioxidant property in Garcinia species are phenolic compounds, flavonoids, phenolic acids, anthocyanins, xanthones and benzophenones, because there is relationship between free radical scavenging and total phenolic content and total flavonoids content (Espirito Santo et al., 2020; Kainama et al., 2020). Another important compound present in the genus Garcinia is hydroxycitric acid, which, together with hydroxylated xanthones and benzophenones, has a significant antioxidant activity. It controls the oxidative stress with hydroxycitric acid and others bioactive compounds from Garcinia regulating the concentration of reactive oxygen species, being one important therapeutic strategy (Han et al., 2021).

Bioactive compounds, such as phenolics compounds, flavonoids and biflavonoids, xanthones and benzophenones, found in this genus are strong antioxidants that complement and enhance the functions of vitamins and enzymes, protecting against oxidative stress (Mello et al., 2021). These compounds may be used in the food industry, mainly in meat products, in which oxidation is one of the main problems related to their deterioration (Beya et al., 2021). Another strong trend in the study of natural antioxidants is their use to preserve the quality of raw food, suggesting another possible application for plant extracts and isolated metabolites that show this property.

Based on the relevant potential of plants as a source of antioxidant compounds, the present review aims to describe the antioxidant property of species of the Garcinia genus, reported between 2017 and 2022.

Data relating to Garcinia spp. and their antioxidant potential were obtained through PubMed and Google Scholar published in the last 5 years. The species of Garcinia shown here were chosen due to the number of publications such as G. mangostana, G. kola, G. xanthochymus and others. Another reason was the relation with metabolic disorders. The following exclusion criteria were adopted: 1- article whose full text was not accessible in the database; 2- publications that did not include the terms “Garcinia” and “antioxidant activity” search phrases in the abstract or title; 3- articles which are not written in English; and 4- articles in which the phytochemicals used in the biological activity assays were not isolated from these species but were acquired from industries. The chemical structures of compounds mentioned in this text were drawn using ChemDrawn 12.0 software.

The terms oxidants or pro-oxidants are related to the reactive oxygen species (ROS) and reactive nitrogen species (RNS). Both of them can be described as free radicals, although ROS can be found as non-free radical species. Free radicals are atoms or molecules containing one or more unpaired electrons in the valence shell (Elmund and Hartrianti, 2020). Because of its odd and unpaired electron, the radical becomes unstable, short-lived, and reactive. Due to their high reactivity, radicals interacts with other substances to remove their electrons and achieve stability. The substance that has suffered the electron remotion can turn into a radical and reacts with a subsequent one and, thus, start a chain reaction, which ultimately causes cellular damage (Kumar et al., 2021; Omidifar et al., 2021). These free radicals can be generated in normal mitochondrial processes. This phenomenon, oxidative stress, occurs when pro-oxidant substances are in higher concentration than antioxidant substances. Then, they may cause oxidative damage due to the absence of antioxidant defense. The examples for the radicals include superoxide (O₂^•-), oxygen radical (O₂^••), hydroxyl (OH•), alkoxy radical (RO•), Peroxyl radical (ROO•), Nitric oxide (NO•) and nitrogen dioxide (NO₂º) (Abubakar et al., 2020; Kumar et al., 2021).

When the number of oxidizing substances, whether free radicals or nonradical reactive species, are at a higher level, the body is able to neutralize by the action of antioxidant substances and, by the enzymatic antioxidant system, the phenomenon oxidative stress occurs. This phenomenon describes the level and state of oxidative damage to tissues and cells caused by ROS and other radicals. Oxidative stress can be defined as an imbalance between concentration of free radical and other oxidative compounds and the decrease of concentration of antioxidants, which lead to a disruption of redox signaling, control and molecular damage (Cassidy et al., 2020; Kumar et al., 2021; Mohamed and Ibrahim, 2020). In mental illness, for example, the concentration of antioxidants and their markers can indicate the level of oxidative damage and suggest the presence of a particular disease or disorder. In this context, the reduction in the level of antioxidants such as glutathione, glutathione transferase and catalase, as well as the increase in ROS and RNS and the variability of their concentrations, may indicate differences in the initial and final stages of healthy problems related to this balance (Ashton et al., 2019).

In order to control the undesired action of radicals, the search for compounds that perform this function is increasing. In this case, these substances are called antioxidants. They can be present in the body and convert radicals and other reactive species into stable species. Antioxidants act by different mechanisms of action, including radical scavengers, singlet oxygen inhibitors, peroxide inactivators and metal chelators (Gulcin, 2020). Redox markers are also used as evaluation parameters for oxidative stress, there is an increase in malondialdehyde and thiobarbituric acid reactive substances markers. The antioxidant enzymes themselves can be used as markers that are altered in the context of serious diseases, such as superoxide dismutase, catalase and glutathione peroxidase, as they indicate the active level of the body’s antioxidant defense. High levels of oxidative stress may originate in the mitochondria and are associated with their dysfunction or, in part, when the oxidative damage to the mitochondria happens (Ashton et al., 2019).

A variety of assays are used to evaluate antioxidant property of secondary metabolites from plants, by different mechanisms. Among them, it is possible to cite assays of radical capture activity or reactive species, reducing power and metal chelation. The most common methods for evaluating antioxidant activity to be used is the radical scavenging activity assay of 2,2-diphenyl-1-picrylhydrazyl (DPPH), radical 2,2’-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP) and metal chelation capacity (Wairata et al., 2022). Depending on the reagents involved, the type of antioxidant and oxidant reactions can occur in two distinct mechanisms in order to convert the radical into a stable species. Both mechanisms lead to the same results (Gulcin, 2020). So, the basis of the chemical reactions involved is categorized into hydrogen atoms transfer (HAT) and single electron transfer (SET). HAT (Eqs. 1 and 2) is defined as one H atom is transferred to a radical target resulting in a stable product and SET (Eqs. 3–6) as one or more electrons are transferred to reduce target free radicals.

(1)

(2)

(3)

(4)

(5)

(6)

Reactions HAT and SET, where AH = any antioxidant with donatable H or electron, PheOH = phenol or polyphenol antioxidants, M = redox metal. Reactions based in SET involve one redox reaction with the antioxidant compound.

Antioxidant assays like DPPH, ABTS and FRAP occur by SET mechanisms. The DPPH radical capture assay is among the most used assays in the evaluation of antioxidant activity (Benzie and Devaki, 2017; Sethi et al., 2020). DPPH is a stable radical of purple color and soluble in ethanol. After reacting with antioxidants, electrons or hydrogen atoms, it loses its purple color, becoming colorless or slightly yellowish. The colorless compound formed is also called 2,2-diphenyl-picrylhydrazyl or reduced DPPH (Gulcin, 2020).

The ABTS^•+ radical is prepared from nonradical ABTS by reacting with a strong oxidizing agent, such as persulfate ion (Sethi et al., 2020). ABTS^•+ is a bluish green cation radical with maximum absorption at 734 nm, which gradually loses its color intensity when it reacts with antioxidant species (AH, Ar-OH) (Gulcin, 2020).

The FRAP of extracts from plant samples occurs through single electron transfer reactions. This is a method that measures the ability of the potential antioxidant to transfer an electron to reduce any compound, in this case the transition metal iron, as well as carbonyls and other oxidizing radicals (Benzie and Devaki, 2017; Sethi et al., 2020). The need to investigate the ability to reduce iron ions in their involvement in the oxidative process, increasing the concentration of ROS, consequently, aggravating the oxidative stress. Iron participates in the Fenton reaction, present in the body (Benzie and Devaki, 2017). Some ROS are moderately reactive such as superoxide (O₂^•-) like most biological molecules. However, through the Haber–Weiss reaction catalyzed by the Fenton reaction, other extremely reactive ROS are generated (Gulcin, 2020). Fe³⁺ reacts with the superoxide to form Fe²⁺ (Eq. 7). This cation reacts rapidly with hydrogen peroxide (H₂O₂) producing ion of iron III, radical hydroxyl and the hydroxyl ion (Eq. 8), ROS that are extremely harmful to the body (Benzie and Devaki, 2017; Lakey-Beitia et al., 2021). The combination of Eqs. 7 and 8 results in the iron-catalyzed Haber–Weiss reaction (Eq. 9), which turns out to be possible in vivo (Engwa, 2018).

(7)

(8)

(9)

The importance of evaluating FRAP is in reducing of the Fe³⁺ in Eq. 7, as this prevents the formation of ROS, whereas in chelation of iron, the antioxidant compounds present in the extracts chelate the ion Fe²⁺ in Eq. 8, also preventing the formation of ROS. In general, the chelation capacity of metals is determined by measuring the chelating effect of antioxidants for iron ions, Fe²⁺ (Gulcin and Alwasel, 2022). The chelating capacity of antioxidant compounds can be measured to chelate both Fe and Cu, and in turn, phenolic and flavonoid species are both able to chelate these transition metals (Lakey-Beitia et al., 2021). The chelation of transition metals prevents them from participating in reactions that generate oxidant species, for example, in Fenton and Haber–Weiss reactions generating ROS (García-Diez et al., 2021).

The major classes of secondary metabolites found in species from Garcinia genus are phenolics compounds, flavonoids, biflavonoids, xanthones, benzophenones and terpenes (Hassan et al., 2018). These phytochemicals can be isolated by different parts of the plant, using different techniques, such as conventional fractionated extraction, ultrasound assisted extraction and microwave assisted extraction (Carrillo-Hormaza et al., 2020; Chang et al., 2020; Ramirez et al., 2019).

The two main classes of bioactive compounds found in species of the genus Garcinia are xanthones and benzophenones, associated with isoprenyl groups and glycosides. The base skeleton of xanthone is composed of two benzene rings linked by a γ-pyran ring, and its tricycle structure can be associated with its biological activities (Ashton et al., 2019; Zafar et al., 2019). The name xanthone comes from Greek language, where xanthos means yellow color, because xanthones are commonly obtained as yellow solids (Kurniawan et al., 2021). Xanthones can be found in various parts of plants from the Garciniagenus, such as the fruit, peel of the fruit, bark, and seeds (Mohamed and Ibrahim, 2020). The biosynthesis of xanthones is given based on the numbering of ring A and B from xanthones. The biosynthesis pathway of ring A (carbon 1-4) comes from the acetate pathway, while the ring B (carbon 5-8) is given by the shikimic acid pathway (Pinto et al., 2021). Several xanthones analogs and their glycosides are obtained by adding substituents to the side chain of the aromatic rings of the skeleton base, but in different positions. Thus, there are reported hydroxylated xanthones, from mono to polyhydroxylated, prenylated, alkylated, linked to charged groups, linked to glycoside groups, linked to alkoxide groups and xanthones found in the form of dimers and trimers (Zafar et al., 2019).

The xanthones found in Garcinia species exhibit important diverse biological properties, such as antioxidant, antitumor, antiviral, anti-HIV, antiglycemic, antimicrobial and neuroprotective activities such as in Alzheimer’s disease, Parkinson’s disease and depression, anticancer (Do and Cho, 2020; Inoue et al., 2017; Kurniawan et al., 2021; Wairata et al., 2022; Wang et al., 2017; Zafar et al., 2019).

The xanthones isolated from Garcinia species exhibit important diverse biological properties, such as antioxidant, antitumor, antiviral, anti-HIV, antiglycemic, antimicrobial and neuroprotective activities (Kurniawan et al., 2021; Wairata et al., 2022; Wang et al., 2017). Examples of these metabolites include α-mangostin, β-mangostin, γ-mangostin, gartanin, 8-desoxygartanin, garcinexanthone A, cabalaxanthone, garcixanthone A, garcinone C, lichexanthone, subelliptenone H, 12b-hydroxy-des-D-garcigerrin A, garciniaxanthone B, garcigerin A, garcinone-E, smeathxanthone A, and 1,3,5-tridroxyxanthone (Fig. 1) (Kusmayadi et al., 2019; Wairata et al., 2022; Zafar et al., 2019).

Benzophenones are a class of compounds similar to xanthones. However, there is no oxygen present between the two aromatic rings. The base form for benzophenones is characterized by phenol-carbonyl-phenol (Inoue et al., 2017; Murthy et al., 2020). They can also be in the form of polyisoprenylated, linked to glycosides and other substituents, as well as xanthones. Examples of known benzophenones are isogarcinol, garcinol and 7-epiclusianone, xanthochymol, 2,4,6,3’,4’,6’hexahydroxybenzophenone. Morelloflavone and volkensiflavone are biflavonoid found in G. brasiliensis (Fig. 2) (Moreira et al., 2017; Pasaribu et al., 2021b). The A ring of benzophenones usually have one or two substituents present. On the other hand, the B ring can undergo prenylation and cyclization, producing a variety of different compounds. The benzophenones can be unique with bi-, tri- and tetracyclic ring systems and show different biological activities, such as antioxidant, antimicrobial, anti-HIV, cytotoxic, hepatoprotective, antiparasitic, and antidiabetic. Benzophenones are the main intermediates in the biosynthetic pathway of xanthones (Inoue et al., 2017).

Figure 1.
Examples of xanthones found in the Garcinia species.

Figure 2.
Examples of benzophenones and flavonoids presents in Garcinia species.

Xanthones and benzophenones can be classified as primary antioxidants because they are capable of donating hydrogen or electrons to ROS. In consequence, they delay, inhibit or prevent the initiation step or interrupt reaction in the chain. Xanthones react with free radicals through electron transfer or hydrogen atom transfer. The antioxidant activity of phenolics compounds may vary according to the amount of hydroxyl substituents and the position of other substituents in the skeleton (Gulumian et al., 2018). This happens because hydroxyl groups attached to aromatic rings, forming phenolic groups, act effectively to capture free radicals. The number of hydroxyl groups present in xanthones, flavonoids and other classes of compounds also affects their antioxidant potential. Although dihydroxy and trihydroxy xanthones or flavonoids have significant antioxidant activity, tetrahydroxy xanthones or flavonoids have higher values than di- and trisubstituted. However, it is necessary to take into account the presence of other substituents that alter the interaction between the xanthone and the oxidizing compound. Among these substituents it can be listed alkoxide, prenyl groups. In addition, several natural xanthones that have antioxidant property also exhibit other activities and the scientific community has developed studies to evaluate the structure-activity relationship to better investigate the biological potential of these molecules (Gulcin, 2020; Gulumian et al., 2018; Zafar et al., 2019).

Virgolin et al. (2017) investigated the antioxidant activity by FRAP assay of extracts of the fruits of G. humilisand G. xanthochymus using 70% acetone. It was observed a good potential for these samples, 2995.88 ± 3.23 and 489.39 ± 0.48 µmol trolox 100 g^–1 pulp, respectively.

Considering the evaluation of isolated compounds from the Garcinia genus, Wairata et al. (2021) investigated the antioxidant, antidiabetic and antiplasmodial properties of xanthones from G. forbesii. From the stem bark of G. forbesii, it was isolated five xanthones: lichexanthone, subelliptenone H, 12b-hydroxy-des-D-garcigerrin A, garciniaxanthone B and garcigerin A (Fig. 2). These authors evaluated the antioxidant property of the compounds described by scavenging DPPH, ABTS, and FRAP methods, and verified that those metabolites showed strong antioxidant activity by those methods. The most effective compounds were garciniaxanthone B for DPPH assay and 12b-hydroxy-des-D-garcigerrin A for ABTS assay. The antioxidant activity of these compounds can be explained by the presence of hydroxyl groups linked in aromatic rings, which react with radical DPPH through the SET mechanism. From G. brasiliensis, fukugetin, 7-epiclusianone and guttiferone-A were found in its fruits and seeds. These compounds performed relevant antioxidant activity (Melo et al., 2021).

Considering the chelation of metals, Chew and Lim (2018) evaluated the FRAP of G. mangostana, G. atroviridis and G. hombroniana extracts from leaves, pulps and pericarps of these species. Considering leaves and pulp extracts, G. hombroniana was more effective in chelating power (60% and 30%, respectively). The pericarp extract of G. mangostana showed more activity (78%) than G. hombroniana and G. atroviridis (45% and 11%, respectively). The parts of the same Garcinia species were compared in terms of antioxidant activity and total phenolic content and total flavonoids content.

Nguyen et al. (2021) evaluated the antioxidant activity of G. fusca, G. hopii, G. planchonii, G. nigrolineata, G. gaudichaudii,and G. tinctoria. The extracts were obtained with hexane, ethyl acetate and methanol in solid-liquid extraction. The antioxidant activity methods used were DPPH assay, hydroxyl radical scavenging and total antioxidant capacity. The higher values of IC₅₀ for the DPPH assay were found in ethyl acetate extract and methanolic extract in all Garcinia species. For hydroxyl radical scavenging capacity, the strongest antioxidant activity is shown in ethyl acetate extract of G. tinctoria with 83.5% at IC₅₀ of 1.5 μg mL^–1. About the total antioxidant capacity assay, the extracts obtained from G. tinctoria have the highest values 265.

Ramirez et al. (2019) evaluated the antioxidant activity by DPPH, ABTS and FRAP assays of seeds, epicarp and leaves of G. madruno. A sequential extraction of these parts with hexane, dichloromethane, ethyl acetate and methanol were done. The ethyl acetate fraction from leaves was more effective in the three assays. Research like this makes possible discussions and analysis between fractions of the same plant part and between all parts studied. The different polarity of solvent used influences directly the yield of antioxidant compounds and the IC₅₀ value of antioxidant activity, solvents such as ethyl acetate, dichloromethane and others with medium polarity are good to extract phenolics compounds. Other articles are shown in Table 1.

Table 1.
Antioxidant property of Garcinia species.

FRAP = ferric reducing antioxidant power; TAC = total antioxidant activity; DPPH = 2,2-diphenyl-1-picrylhydrazyl scavenging assay; ABTS = 2,2’-azinobis-(3-ethylbenzothiazoline-6-sulphonate) radical scavenging assay.

It is important to highlight that many researchers report the relationship between antioxidant activity with other biological activities or alternative methods of extraction. Between them, the research of Chang et al. (2020) was based on the effect of a concentrated mangosteen (G. mangostana) drink, MCD, in rats after long-term running exercise in order to investigate changes in the antioxidant system and lactate clearance. Since aerobic exercise can lead to significant fatigue, oxidative stress and muscle damage, the authors investigated the level of lactate clearance and the levels of endogenous antioxidants such as superoxide dismutase, glutathione peroxidase and catalase, in addition to blood glucose, cholesterol, triglycerides and muscle malondialdehyde levels. The levels of glutathione peroxidase and catalase increased with the ingestion of concentrated mangosteen drink and the supplementation of this drink also increased lactate clearance, contributing to a better physical recovery of rats after exhaustion from running exercise. MDA concentration also decreased with mangosteen drink supplementation compared to the control group; however, there was no decrease of malondialdehyde in muscle.

Araújo et al. (2019) performed in vivo tests in mice that were ingesting ethanolic extract of G. brasiliensis leaves daily to evaluate its antioxidant activity, modulation of the intestinal microbiota and anti-inflammatory activity. The ethanolic extract of the leaf contained the biflavonoid morelloflavone and the benzophenone 7-epiclusianone. They concluded that the extract was able to reduce oxidative stress, demonstrated by the increase in the amount of antioxidant enzymes. It inhibited the inflammatory process, modulated the intestinal microbiota, favoring beneficial bacteria and regulating lipid metabolism, which reduces obesity (Araújo et al., 2019). The ethyl acetate extract of the seeds e from G. kola was evaluated by Idris et al. (2020) for in vivo antioxidant, anti-inflammatory and antidiabetic activities. Biochemical markers related to these processes such as glutathione peroxidase levels, lipid peroxidation revealed by malondialdehyde levels and biochemical markers for antidiabetic activity were evaluated. The levels of glutathione found in the group administered with G. kola were near to the healthy group, but the highest value was found in the treated group with insulin. The malondialdehyde levels increased in the group treated with insulin and the G. kola extract group compared to diabetic control group. These results emphasize that G. kola extract is a candidate for therapeutic uses in diabetes and oxidative stress treatment (Idris et al., 2020). Tjahjani, et al. (2019) demonstrated antioxidant and antimalarial activity of G. mangostana’s ethyl acetate fraction for in vivo models.

All these reports highlight the relevant scientific potential of species from the Garcinia genus and stimulate the search for new sources of antioxidant compounds.

Garcinia genus shows significant free radical scavenging and antioxidant potential by the presence of xanthones and benzophenones. The isolated compounds and extracts from these species have potential to be applied in pharmaceutical and food industries. This emphasizes the continuation of studies involving these plants, because they can lead to the discovering new possibilities of application of these natural resources, increasing their scientific value.

Conceptualization: Kazmierczak, E.; Pereira, R. P.; Magalhães, C. G.

Data curation: Kazmierczak, E.

Formal analysis: Kazmierczak, E.

Funding acquisition: Not applicable.

Investigation: Kazmierczak, E.

Methodology: Kazmierczak, E.; Pereira, R. P.; Magalhães, C. G.

Project administration: Kazmierczak, E.; Pereira, R. P.; Magalhães, C. G.

Resources: Kazmierczak, E.

Software: Not applicable.

Supervision: Pereira, R. P.; Magalhães, C. G.

Validation: Pereira, R. P.; Magalhães, C. G.

Visualization: Kazmierczak, E.; Pereira, R. P.; Magalhães, C. G.

Writing – original draft: Kazmierczak, E.

Writing – review & editing: Pereira, R. P.; Magalhães, C. G.

The data will be available upon request.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). Finance Code 2013/2998/2014.

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). Grant No: 307546/2014.

Not applicable.