Ana Clara Brito Maria¹, Thaíse Reis Simões¹, Aline de Souza Ramos¹, Maíra Martins Haddad de Almeida¹, Maria Athana Mpalantinos da Silva¹, Jefferson Diocesano da Cruz¹, José Luiz Pinto Ferreira², Jefferson Rocha de Andrade Silva³, Ana Claudia Fernandes Amaral^1,*

¹Laboratory of Medicinal Plants and Derivatives, Department of Natural Products, Farmanguinhos, Fiocruz, Rio de Janeiro, BRAZIL.

²Faculty of Pharmacy, Federal Fluminense University, Niterói, BRAZIL.

³Chromatography Laboratory, Department of Chemistry, Federal University of Amazonas, Manaus, BRAZIL.

¹Correspondence

Dr. Aline de S Ramos,

Laboratory of Medicinal Plants and Derivatives, Department of Natural Products, Farmanguinhos, Fiocruz, Rio de Janeiro, BRAZIL.

E-mail: [email protected]

²Correspondence

Dr. Ana Claudia F Amaral,

Laboratory of Medicinal Plants and Derivatives, Department of Natural Products, Farmanguinhos, Fiocruz, Rio de Janeiro, BRAZIL.

E-mail: [email protected]

History

• Submission Date: 03-09-2021;

• Review completed: 05-10-2021;

• Accepted Date: 17-11-2021.

DOI : 10.5530/phrev.2022.16.8

Article Available online

http://www.phcogrev.com/v16/i31

Copyright

© 2022 Phcog.Net. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

INTRODUCTION

Spondias mombin Linnaeus (Anacardiaceae) is a plant species found from southeastern Mexico to Peru and in the northern and northeastern regions of Brazil. S. mombin is commonly known as “ciruella amarilla” in Mexico and Ecuador; “cajá” in Brazil; and “yellow mombin” in North America, among others.^[1,2] Some of the medical uses include the leaves in the treatment of wounds and inflammations; the infusion preparation of its flowers against stomachache, constipation, and bilious fevers; the decoction of the roots as antidiarrheal; and the decoction of its barks to treat emesis, diarrhea, and hemorrhoids.^[3-5] Many studies have shown important properties in S. mombin, such as antiviral, anti-inflammatory, antioxidant, and antibacterial properties, mainly attributed to flavonoids, saponins, and phenolic acids isolated from leaves.^[6-9]

In 2004, our research group developed a monograph as a narrative review of the chemical properties of S. mombin that was published as a book chapter.^[10] However, there are many other properties described in the literature, including in vivo and in vitro studies, that were not covered in our previous chapter or another review article. Thus, this study aimed to gather new information about the properties of S. mombin and the progress of new products containing this plant species, contributing to the scientific community.

METHODS

Systematic studies were conducted using Science Direct, Scholar Google, and PubMed as databases. The keywords used to find the articles were “Spondias mombin” combined with “activities”, “biological activities”, “formulation”, “nanoparticle”, “nanotechnology”, “popular use”, “folk medicine”, “chemical profile”, “constituents”, “physicochemical analysis”, “botanical”, “distribution”, “uses”, “popular names”, and “characterization”. The year of publication was not used as a criterion, and the language was limited to Portuguese and English.

In the search for patents, a data survey was carried out in April 2021 in the following patent search databases using “Spondias mombin” as the keyword: European Patent Office (EPO), United States Patent and Trademark Office (USPTO), World Intellectual Property Organization (WIPO) and Instituto Nacional de Propriedade Industrial (INPI).

BOTANICAL ORIGIN

Spondias mombin Linnaeus belongs to the Anacardiaceae family, which includes 73 genera and approximately 850 species.^[11] Some synonyms are S. aurantiaca Schum and Thonn, S. axillaris Roxb., S. dubia A. Rich., S. graveolens Macfad., S. lutea var. glabra Engl., S. lutea var. maxima Engl., S. lutea var. pseudomyrobalanus (Tussac) Marchand, S. nigrescens Pittier, S. pseudomyrobalanus Tussac, S. oghigee G. Don, S. purpurea var. venulosa Engl., S. radlkoferi Donn. Sm., S. venulosa (Engl.) Engl., S. zanzee G. Don.^[12]

POPULAR USES

All parts of S. mombin can be used for nonmedicinal or medicinal purposes. Among the nonmedical uses, bark is used in carving Figures and as a dyeing agent, while leaves are used as vegetables. Flowers are used for decoration, and nectar can be used for honeybees. The root is considered a water source, while the stems are used in living farmland and as a shelter by artisans. Wood is used in carpentry to make different objects, such as pencils and match sticks. In Brazil, it is used as a bottle stopper and in the manufacture of sealing wax. In Costa Rica it is also used as fuel. Wood ash was used as an indigo dye, and gum was used as glue. The fruits are used to alleviate thirst; to prepare ice cream, cool beverages, and jelly in Costa Rica and Brazil; to produce wine in Amazon - known as “Vinho de Taperiba” - and a cider-like drink in Guatemala.^[3]

The medicinal uses described in the literature are summarized in Table 1.

POPULAR NAMES

The fruits of S. mombin are known as “cajá miúdo” or “cajá pequeno” in Southeast and Southern Regions of Brazil and as “taperebá” and “acajá” in the Amazon region. The names “taperebá” and “acajá” are of indigenous origin (Tupi): the first word means “tapir fruit” (from “tapir”, tapir and “iba”, fruit) and the second “stone fruit” (from “acâ”, stone, and “ya”, fruit).^[2] Reports in the literature indicate that S. mombin was cultivated by indigenous people in the 16^th and 17^th centuries.^[13,14] Other common names among regions are “prunier mombin” in French Guiana, “ciriguela del monte” and “jacote” in Guatemala, “azucaró” and “cedrinho” in Bolívia, “ciruella amarilla” in Mexico and Ecuador. The fruit is also known as “jobo” in Central America and Venezuela, as “hogplum” or “yellow mombin” in North America, as “ambaló” in Goa, and as “munguengue” in Angola.^[15] Other vernacular names are “macaprein”, “hoba” and “yellow plum” in Netherlands Antilles; “jobillo” and “jobo vano”, “jobo de perro” in Puerto Rico; “ciruela”, “joboban”, “jobo de poerco” in Dominican Republic; “mope”, “moppe”, “hooboo” in Suriname; “risco”, “orocoro-cillo”, “hobo”, “jobo”, “jobo blanco”, “jobo colorado”, “jobo arisco”, “jobo del amazonas”, “jobo de castilla” in Colombia and “job female” in Cuba.^[16]

GEOGRAPHICAL DISTRIBUTION

S. mombin is native to moist lowland forests from southern Mexico to Peru and Brazil and is also found in many of the West Indies. It is widely cultivated and naturalized in tropical Africa.^[1] The species is found in Chile, Argentina, Colombia, Bolivia, Panama, Nicaragua, Suriname, Ecuador, French Guiana, Puerto Rico, Guyana, Paraguay, Uruguay, Honduras, Guatemala, and Venezuela.^[17] In Brazil, its occurrence is confirmed in almost all regions, mainly in the North and Northeast, and except in the South.^[15,18]

BOTANICAL DESCRIPTION

CHEMICAL CONSTITUENTS

Before performing the biological assays, it is important to highlight the extraction method, isolation, and detection/identification of the chemical constituents of the extracts. The summary of this section, as well as their respective results, is shown in Table 2.

Table 2 shows the chemical composition studies focused on the extracts obtained from leaves of S. mombin prepared by maceration using a hydroethanolic solvent.

Regarding the classes and compounds most frequently identified and/or isolated, there are several phenolic compounds, especially ellagic acid, chlorogenic acid, and quercetin derivatives (Figure 1).

It is important to emphasize that these were the classes and compounds most found due to the choice of the extraction method (maceration) and solvents (polar). These metabolites can be altered by changing these factors, as observed by the presence of terpenes through the hydrodistillation process.

PHYSICAL AND CHEMICAL ANALYSIS

In physical characterization, Mattieto et al. (2010),^[28] measured 100 fruits of S. mombin, obtaining an average length of 2.93 ± 0.60 cm, width of 2.18 ± 0.27 cm, weight of 7.19 ± 3.20 g, and density of 0.94 ± 0.38 g/cm³. The mass yields represented 24.2 % pulp, 13.8 % bark, 51.8 % seeds, and 10.2 % losses.

The results of the physical-chemical characterization of the pulps were 2.53 ± 0.01 (pH), 1.86 ± 0.01 % citric acid (total titratable acidity), 10.09 ± 0.00 ºBrix (soluble solids), 5.42 ± 0.01 (ratio), 89.42 ± 0.18 % (moisture), 0.82 ± 0.01 % (protein), 0.26 ± 0.09 % (total lipids), 0.58 ± 0.02 % (ash), 1.18 ± 0.10 % (dietary fiber), 0.43 ± 0.12 % (insoluble fiber), 0.75 ± 0.12 % (soluble fiber), and 4.54 ± 0.25 g. 100 g^-1 (total sugars), 4.25 ± 0.34 g. 100 g^-1 (reducing sugars), 0.29 ± 0.27 g. 100 g^-1 (nonreducing sugars), 28.30 ± 0.18 µg. g^-1 (total carotenoids), 299.81 ± 0.48 mg. 100 g^-1 (tannins), and 23.72 ± 0.08 mg ascorbic acid. 100 g^-1 (vitamin C).^[28]

In addition, the spectrophotometer results were 61.02 brightness, 14.73 chromaticity +a (red), and 41.50 chromaticity +b (yellow), which showed the predominance of the yellow color in the fruit.^[28]

The total phenolic content of the methanol extract of S. mombin fruit (MESSM) was determined using Folin-Ciocalteu phenol reagent and resulted in 239.50 ± 7.9 mg gallic acid equivalents/g. The total flavonoid content was determined by the aluminum chloride chelation method and indicated 105.3 ± 3.6 mg rutin equivalents/g. For antioxidant predictions, the 50% inhibitory concentration (IC₅₀) was calculated through 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydrogen peroxide, and nitric oxide assays, indicating 58.64 ± 1.49, 44.03 ± 5.57 and 494.55 ± 12.68 µg/mL, respectively, and the control (ascorbic acid) showed values of 4.31 ± 0.26, 10.63 ± 0.31 and 48.74 ± 1.46 µg/mL, respectively. According to the authors, it appeared to be the first experiment reporting the probable antioxidant properties with these tests, which shows that there is much to be studied about S. mombin.^[29]

The hydroxyl radical scavenging and the reducing power assay of the essential oil (EO) of S. mombin leaves obtained by Oladimeji et al. (2016)^[30] were analyzed by two methods: one using ferrous sulfate, H₂O₂, and salicylic acid and the other using potassium hexacyanoferrate, trichloroacetic acid, and ferric chloride (FeCl₃). The EO produced 83 % (fresh leaves) and 99.8 % (dried leaves) scavenging effects (hydroxyl radicals) at a concentration of 1 mg/L, similar to Vitamin C, which exhibited approximately 90 %. These tests showed that EO is effective in halting the oxidation of cellular macromolecules and that its volatile compounds depend totally on scavenging hydroxyl radicals.

Two studies described in the section “Anti-inflammatory activity” have verified the antioxidant properties. Gomes et al. (2020)^[8] prepared a hydroalcoholic extract (HE) from S. mombin leaves and measured the total glutathione levels (GSH) in the buccal mucosa of hamsters by adding ethylenediamine tetraacetic acid (EDTA) solution and after mixing the supernatant with Tris buffer (pH 8.9) and 5,5′-dithiobis-(2-nitrobenzoic acid in each sample (4 per group). The values were determined through absorbance measurement at 420 nm. The results demonstrated the ability of S. mombin to prevent the reduction of GSH levels in the buccal mucosa. It is important to highlight the presence of two major phenolic compounds in the extract with potent antioxidant properties: chlorogenic acid (19.4 mg/g) and ellagic acid (12 mg/g).

The study performed by Cabral et al. (2016),^[7] showed that HE, the butanol extract, and chlorogenic acid from the leaves were able to sequester 74.53, 73.71, and 91.47 % of free radicals, respectively, according to the DPPH assay. In addition, all these samples could sequester more than 100 % when tested for hydroxyl radical scavenging activity, similar to gallic acid at 15 mg/mL (control). This result also contributes to the suggestion that the antioxidant properties are related to these phenolic acids.

Other researchers who verified the antioxidant properties were Cristofoli et al. (2019).^[9] They prepared some extracts from S. mombin leaves: one of them was carried out through a Soxhlet apparatus (Sox) using 150 mL of hexane, ethyl acetate, ethanol, water, or a mixture of ethanol:water (1:1 v/v). Another extraction was conducted through ultrasound-assisted extraction (UAE) using the same solvents in the same proportion for 8 min with a 50 % sonication amplitude (250 W). Then, supercritical fluid extraction (SFE) was performed with 15 g of the sample and CO₂. After the extractions, the total phenolic content (TPC) was determined by the Folin-Ciocalteu method, and the antioxidant properties were verified through the free radical scavenging activity by DPPH and the ABTS⁺ [2,2-azino-bis-(3-ethyl benzothiazoline-6-sulfonic acid)] method.

The best yields were obtained using a Soxhlet apparatus with ethanol (22.5 ± 0.5 %), ethanol + water (23.5 ± 4.4 %), and water (21.6 ± 4.7 %) as solvents and by UAE using ethanol + water (30.5 ± 0.7 %) and water (27.5 ± 1.7 %) as solvents. Considering the highest TPC values, the extracts obtained through the Soxhlet apparatus (EtOH, EtOH + water, and water), SFE (residue), and UAE (EtOH) resulted in a range between 293.0 ± 6.9 and 410.1 ± 33.1 mg GAE/g extract, which were also considered good.^[9] This study demonstrated that different techniques and solvents used in the extractions are extremely important to achieve the desired results.

BIOLOGICAL ACTIVITIES

SIDE EFFECT, CONTRAINDICATION, ADVERSE REACTION, AND PRECAUTION

In the study performed by Silva (2015),^[50] a sample composed of total solids from S. mombin leaves (HESm), after hydroethanol (70 %) extraction, was used to treat Wistar rats (Rattus novergicus). After the quantitative analysis of its constituents, the acute toxicity was determined through oral application of HESm at 5 g/kg and observation at 30, 60, 120, 180, and 240 min, as well as 14 days after administration.

To verify repeated dose toxicity in the Wistar rats, the animals were treated with doses of 200, 500, and 2000 mg/kg for 30 days, and at the end, their blood was collected. Necropsy was also performed to analyze the external characteristics of some organs. The treatment of pregnant rats was administered at the same doses of the repeated-dose toxicity test in the first six days to observe reproductive toxicity.^[50]

No signs of acute toxicity, death, piloerection, diarrhea, or change in locomotor activity were observed, and only a decrease in food consumption occurred in the first week. Considering the hematological profile of male rats, there was a reduction of 6.1 % in the erythrocyte count at 200 mg/kg and 8 and 6.36 % in the values of average corpuscular volume (ACV) and average corpuscular hemoglobin (ACH), respectively, at 2000 mg/kg and an increase of 20.5, 414 % and 44 % in the range values of red cells, basophils, and monocytes, respectively, at the same dose. No difference was found in the levels of glucose, urea, creatinine, aspartate aminotransferase, total cholesterol, triglycerides, alkaline phosphatase, total, direct and indirect bilirubin, lactate dehydrogenase, and total proteins, but a reduction of 38.76 % in alanine aminotransferase levels and an increase of 27.5 % in glucose levels were observed at 200 mg/kg.^[50]

Microscopic analysis of the organs revealed a small lymphocytic infiltrate in the liver of rats at concentrations of 500 and 2000 mg/kg and a small increase in the renal capsular space, but no alterations were found in the other organs. No death was found among the pregnant rats, and no toxicity signs were observed; only a reduction in the gain of corporeal mass and an increase in water consumption were observed. Fetuses, ovaries, and placental masses had no change, and no external macroscopic malformations in the fetuses or changes in the number of implantations and resorption were observed. These results show that no oral toxicity was found, but attention should be drawn to possible maternal toxicity during the preimplantation period.^[50]

Another study considering the toxicity of S. mombin was conducted, but this time by Luz (2014).^[51] The ethanol extract of S. mombin bark was tested at concentrations of 1000, 750, 500, 250, 100, and 20 µg/mL against Artemia salina nauplii. Toxicity assays were also performed through oral administration of the extract at 2000 mg/kg in Swiss mice. As a result, the LC₅₀ values of 482.5 ± 36.1 and 383.2 ± 34.1 µg/mL at 24 and 48 hr, respectively, showed high toxicity in this predictive experiment with Artemia salina; however, contrasting with this result, there was no acute toxicity at the highest dose (2000 mg/kg) in Swiss mice, in which the animals presented few alterations in the behavioral parameters. No changes were observed in the vital organs, such as the heart, kidney, liver, and lung, and the consumption of water and food remained the same. The authors concluded that the absence of a lethal dose can show its safety for popular uses.^[51]

However, Asuquo et al. (2012)^[52] concluded that although S. mombin is relatively safe, hepatic and renal toxicity can occur with the prolonged use of its leaf extracts. The experiments were conducted with a sample produced through cold extraction with water or ethanol for 72 hr using fresh leaves. The rats received the extracts daily for twenty-eight days and were divided into five groups: A (control), B (250 mg/kg ethanol extract), C (500 mg/kg ethanol extract), D (250 mg/kg aqueous extract), and E (500 mg/kg aqueous extract). Then, blood was drawn from the heart for further analysis. Some organs, such as the liver, heart, lungs, kidneys, stomach, spleen, gonads, and brain, were excised and weighed at the end of the experiments.

As a result, no toxicity and no death were observed in the acute toxicity test, but body weight loss in the treated animals was noted. A significant decrease in food consumption was recorded in the fourth week of treatment in groups C and E, which exhibited values of 42.54 ± 6.22 g and 56.00 ± 7.96 g, respectively, in contrast to the control, which showed approximately 108.65 ± 6.65 g of food. In the same groups, there was an increase in water consumption during the fourth week of extract administration, with water intakes of 234.88 ± 7.12 (group C), 258.55 ± 8.21 (group E), and 258.55 ± 8.21 mL (control). Brain, kidneys, and spleens were significantly different from control in group E with relative mean weight values of 0.64 ± 0.66, 0.42 ± 0.02, and 0.40 ± 0.05, respectively, while the control showed 0.40 ± 0.05, 0.40 ± 0.05, and 0.52 ± 0.04 to the same organs. Group C also showed a difference in the spleen, with a relative mean weight of 0.41 ± 0.01. Through observation of some liver biochemical parameters, it was possible to note that the low density lipoprotein and albumin values were reduced significantly according to the serum biochemical parameters. The hematological indices remained acceptable.^[52]

Moussa et al. (2018)^[53] tested the toxicity of an aqueous extract of the stem bark of S. mombin in Winstar albino rats. The extract was made through maceration of 50 g of the leaf powder in 1 L of distilled water, followed by filtration, concentration, and drying in an oven. Three oral doses (250, 500, and 1000 mg/kg) and one control (distilled water) were given to the rats for twenty-eight days, and blood samples were collected on days 7, 14, 21, and 28. At the end of the experiment, the liver and kidneys were removed, weighed, and assessed for necrosis, steatosis, congestion, hypertrophy, and calcification.

The authors observed that the administration of the extract at the two highest concentrations caused a decrease in the red blood cell count, and a decrease in the hemoglobin level reflecting anemia and in hematocrits at all dosages was also noted. Different disturbances of erythrocytes, target red blood cells associated with hypochromia, and schizocytes were significantly observed in the rat blood. The hemolysis test resulted in an increase in this parameter according to the time in the tubes containing 12.5 mg/mL S. mombin extract. After 28 days, the anatomohistological study revealed steatosis and apoptosis in the liver and necrosis and calcification in the kidney at 500 and 1000 mg/kg. These results could demonstrate certain toxicity of the extract of S. mombin ,^[53] but future studies must be done to determine a safe concentration for use.

FORMULATIONS

Drugs are rarely administered in their pure form, and the most common way is through formulations or medications. Additionally, a good formulation can increase therapeutic efficacy or decrease adverse effects.^[54]

Oiseoghaede et al. (2021)^[55] formulated an ethanol (70 %) extract from the leaves of S. mombin and Abelmoschus esculentus obtained through maceration for 72 hr. The extract has antioxidant properties. To produce an emulsion, 1 g of methylcellulose and mucilage were triturated and mixed with a solution of S. mombin (75 mg) and distilled water. Then, 40 mL of liquid paraffin and distilled water were added, resulting in a 37.5 % solution prepared through the addition of 200 mg of the extract in 200 mL of water.

The results showed a yield of 2.31 % of A. esculentus and 25.75 % of S. mombin and high stability of the emulsion, with pH = 6.88. The DPPH assay showed that the introduction of mucilage was adequate for use as a good emulsifier, although it decreased the antioxidant properties of the formulation.^[55]

In another study, Guedes (2018)^[56] used S. mombin pulp as an active ingredient in cosmetics. Body cream was produced as follows: the raw material in Table 3 was heated to 80°C to form phase 1. For phase 2, the corresponding raw materials were heated to the same temperature. Water at 40°C and xantan gum composed Phase 3. Therefore, phase 1 was poured into phase 2 and then cooled to < 40°C. Finally, the other materials were added, including the fragrance solubilized in propylene glycol, and the pH was adjusted with citric acid.

After this, a face cream was also formulated. To form phases 1 and 2, the same procedures as the body cream were performed. In phase 3, water at 40°C was used to disperse xanthan gum and aluminum starch octenyl succinate. The final steps were similar to those performed for the body cream, except for the pH, which was adjusted to 4.5 - 5.0. For a sensory analysis, acceptance tests of the volunteers were used, in which appearance, fragrance, spreadability, softness, luminosity, hydration, and firmness were evaluated.^[56]

After concluding the formulations, the researchers interviewed some volunteers regarding the possible purchase of body cream. Their answers pointed out that 37 % of the volunteers would certainly buy the products, and 37 % would possibly buy them. Most of the interviewees approved the items, and 79 % of the facial cream volunteers would certainly buy it, showing a difference that may be related to spreadability.^[56]

A hydration analysis with Corneometer CM825 showed that the body product containing 3 % S. mombin kept the skin hydration normal and not dry, as it was before the test performance. The formulations also reduced transepidermal water loss, except for the facial product at a concentration of 1.5 %. According to the author, these results show that S. mombin may be a great component of formulations to treat dried skins.^[56]

Two other formulations were developed with the pulp of S. mombin, but this time by Ramos and Silva (2018).^[57] For the shampoo formulation, the corresponding raw materials were mixed to form Phase 1 (Table 3). With heated water, the other respective raw materials were solubilized at 80°C to form Phase 2. Finally, Phase 3 was formed by joining phases 1 and 2, followed by the addition of the remaining material.

For conditioner development, the raw material in Table 3 was heated to 80°C to form Phase 1. The raw materials related to Phase 2 were mixed in water and heated to the same temperature. After forming Phase 3, cetyltrimethylammonium chloride was added. Then, the mixture was cooled to < 40°C. Finally, the remaining raw material was added.^[57]

After the formulations were developed, some analyses were performed with volunteers. Regarding the brightness of the hair strands, the reflectance (GU) was 3.08, 0.78, 1.64 and 1.56 to 0.8 (without pulp), 1.5 (0.5 %), 3.98 (1.5 %), and 1.06 (3.0 %) after washing, showing by comparison among them and the control, that S. mombin is associated with brightness and that higher concentrations may not be beneficial, unlike when at 0.5 and 1.5 %. It is important to note that the shampoo and the conditioner without pulp were the least pleasing, according to the volunteers. Therefore, the pulp of S. mombin can improve shine, softness, and combing of threads, proving to be a good active ingredient.^[57]

NANOTECHNOLOGY

In addition to the study developed by Asomie et al. (2021),^[39] which shows the antibacterial activity against different bacterial strains caused by synthesized silver nanoparticles (NPs) with the aqueous extract of S. mombin seeds, another study was carried out to produce NPs, but this time, Tijani et al. (2019),^[58] performed a green synthesis of this nanoformulation.

The researchers extracted powdered leaves of S. mombin with water by reflux with 400 cm³ of distilled water for 2 hr. After concentration, 10 cm³ of the extract was added to 100 cm³ of a 0.06 M ammonium paratungstate solution, heating them at 120°C for 30 min. Then, 10 % HNO₃ was added to correct the pH to 1 - 4, while 0.5 M NH₄OH was used to increase it to between 7, 10, and 13. Finally, the solution was separated from the precipitate.^[58]

Quantitative analysis showed the presence of 0.9674 mg/mL total flavonoids, 13.0842 mg/mL total phenols, and 3.5022 mg/mL total tannins. To verify the structural and morphological changes of the nanoparticles at different pH values, high-resolution scanning electron microscopy (HRSEM) was performed, showing that their sizes increased at pH 1, 4, 7, and 10 by 13.8, 14.3, 16.7, and 17.6 nm, respectively. To verify the effects of calcination on the size and shape, the nanoparticles were heated to 250°C, 350°C, 450°C, 550°C, and 650°C for 2 hr each. Their shapes changed according to the temperature: at 250°C, the NPs were highly densely agglomerated and small with no definite or irregular shape; at 350°C, their shapes were spherical with larger agglomerates of large particles; at 450°C, they were thick but spherical, and fewer agglomerated particles were formed; at 550°C, they were spherical, more granular in nature and had a lower dense structure; and at 650°C, there were closely packed spherical-shaped WO₃ nanoparticles. These results demonstrate how the formation of nanoparticles occurs by green synthesis with S. mombin leaf aqueous extract and tungsten trioxide.^[58]

S. mombin was also used to assist ZnO nanoparticle synthesis in solar cells, according to a study performed by Reshma et al. 2021.^[59] The first sample was prepared without the species by dissolving 14.875 g of zinc nitrate and 5.625 g of glycine in 100 mL of distilled water at 400 °C for combustion and then at 500°C to obtain pure ZnO. The second was prepared by zinc nitrate (14.875 g) dissolution in distilled water (50 mL) followed by the addition of S. mombin juice pulp extract (30 mL). ZnO NPs were formed after combustion at 375°C but were collected after calcination at 500°C. X-ray diffraction, field emission scanning electron microscopy (FESEM) and high-resolution transmission electron microscopy (HRTEM) analysis showed nonagglomerated, quasi-spherical particles with diameters of 28.13 and 18.32 nm for samples 1 and 2, respectively. The nanoparticles with the S. mombin extract as the photoanode demonstrate conversion with an efficiency of 0.63 % for a dye-sensitized solar cell produced, which is 12.5 % higher than that synthesized through the traditional method. This method was shown to be simple, economically feasible, and eco-friendly.^[59] It could be noted that the addition of S. mombin pulp did not increase the particle size but resulted in even smaller nanoparticle sizes, which can be considered a good result.

PATENTS

After the data survey, 67 patent orders and patents of Spondias mombin were found, as shown in Table 4.

This table shows 67 patent applications and/or registrations, which demonstrates wide applicability related to the use of S. mombin as a new method of extraction, as an antimicrobial agent, its use in the food industry, green synthesis, phytotherapy uses, pharmaceutical and cosmetic formulations and new types of delivery systems. Thus, there is great potential for the use of S. mombin, with the possibility of developing new methods and developing new products at, for example, the industrial scale.

CONCLUSION

Many different studies on the chemical composition and biological activity of S. mombin have been developed over the years, and through this literature analysis, it was possible to conclude that, related to the chemical composition, different metabolites can be isolated depending on the extraction method, and almost all the extractions resulted in the isolation of the most common phenolic compounds: ellagic acid, chlorogenic acid, and quercetin.

This plant presents some properties that allow it to be used in pesticides. In vitro and in vivo studies confirmed the popular use of S. mombin, showing antioxidant properties and therapeutic activities such as anti-inflammatory, antiulcer, antidiabetic, antiviral, antibacterial, and anthelminthic activities. It was possible to notice its use in cosmetic formulations and nanoformulations. These same activities and formulations were also explored by different researchers, originating patents.

Thus, this review showed that most of the studies use the leaves of S. mombin to study its chemical composition, often using maceration as the extraction method with hydroethanol solvent and that there is a lack of studies about the microscopy of S. mombin barks, which could enrich further studies. Furthermore, there is great potential to transform S. mombin into products, mainly those of therapeutic and cosmetic interest. For this, it is necessary to continue to develop preclinical and clinical studies. We also suggest the performance of scale-up studies, which will also be needed to accomplish this purpose of development.

ACKNOWLEDGEMENT

The authors would like to thank the National Council for Scientific and Technological Development from Brazil (CNPq) and Farmanguinhos for financial support (PROEP-CNPq grant n°. 407856/2017-0). ACBM would like to thank CNPq for the Scientific Initiation Scholarship (PIBIC Program). TRS, MMHA, and JDC are Master’s degree students in Academic Postgraduate Program in Translational Research in Drugs and Medicines, and they thank the Coordination for the Improvement of Higher Education Personnel (CAPES) and Fiocruz for their scholarships.

CONFLICT OF INTEREST

The authors declare no conflict of interest.

ABBREVIATIONS

% VI: percentage of viral inhibition; 5-FU: 5-fluoro uracil intraperitoneal injections; AAIS: amphetamine and apomorphine-induced stereotyped; ABTS+: 2,2-azino-bis-(3-ethyl benzothiazoline-6-sulfonic acid); ACV: average corpuscular volume; ACH: average corpuscular hemoglobin; ADM: agar diffusion method; antiMtb: anti-Mycobacterium tuberculosis test; BHT: butylated hydroxytoluene; CC₅₀: 50% cytotoxic concentration; DAD: diode-array detector; DMSO: dimethylsulfoxide; DPPH: 2,2-diphenyl-1-picrylhydrazyl; EA: ellagic acid; ED₅₀: median effective abortifacient dose; EDTA: ethylenediamine tetraacetic acid; EF: ethyl acetate fraction; ELISA: enzyme linked immuno sorbent assay; EO: essential oil; EPO: European Patent Office; ESI-MS: electrospray ionization mass spectrometry; ESM: Spondias mombin extract; EtOAc: ethyl acetate; EtOH: ethanol; FESEM: field emission scanning electron microscopy; GA: gallic acid; GAE: gallic acid equivalent; GC-MS: gas chromatography mass spectrometry; GR: geraniin; GSH: total glutathione level; HE: hydroethanol extract; HELSm: hydroethanol extract from S. mombin leaves; HESm: total solids from S. mombin leaves (HESm); HF: n-hexane fraction; HIST: hexobarbital-induced sleeping time; HPLC: high performance liquid chromatography; HRTEM: high-resolution transmission electron microscopy; IC₅₀: 50% inhibitory concentration; INPI: Instituto Nacional de Propriedade Industrial; i.p.: intraperitoneal route; LC₅₀: 50% lethal concentration; LC-DAD-MS/MS: liquid chromatography tandem mass spectrometry; LD₅₀: 50% lethal dose; MABA: microplate alamar blue assay; ME: methanol extract; MESSM: methanol extract of S. mombin fruit; MF: methanol fraction; MT: mechanical trauma; MTT: 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide; N: normal (without mechanical trauma); NEU: Neu’s reagent; NIDDM: noninsulin-dependent diabetes mellitus; NIR: novelty-induced rearing; NPs: nanoparticles; ODS: octadecyl phase or reversed-phase C18 Column; PMA: phorbol-12-myristate-13-acetate; MPO: myelo peroxidase; qRT-PCR: real-time polymerase chain reaction; SmEE: S. mombin ethanol extract; Smi: S. mombin fractions obtained by VLC from methanol extract; Sox: extracts obtained through the Soxhlet apparatus; SFE: supercritical fluid extraction; TCID50: the median tissue culture infectious dose; TLC: thin layer chromatography; TPC: total phenolic content; UAE: ultrasound-assisted extraction; USPTO: United States Patent and Trademark Office; VLC: vacuum liquid chromatography.

REFERENCES

 1. Yellow Mombin MJ [internet]. Miami: fruits of warm climates; c2021 [cited Apr 21 2021]. Available from: https://hort.purdue.edu/newcrop/morton/yellow_mombin_ars.html.

 2. Spruce R. Notas de um botânico na Amazônia. Belo Horizonte, Itatiaia; 2006.

 3. Ayoka AO, Akomolafe RO, Akinsomisoye OS, Ukponmwan OE. Medicinal and economic value of S. mombin. Afr J Biomed Res. 2008;11:129-36.

 4. Cruz GL. Livro verde das plantas medicinais e industriais do Brasil. Belo Horizonte: Oficinas Gráficas de Veloso; 1965.

 5. Duke JA, Vasquez R. Amazonian ethnobotanical dictionary. Boca Raton: CRC Press Press; 1994.

 6. Silva A, Morais SM, Marques MMM, Lima DM, Santos SCC, Almeida RR, et al. Antiviral activities of extracts and phenolic components of two Spondias species against dengue virus. JVATiTD. 2011;17(4):406-13.

 7. Cabral B, Siqueira EMS, Bitencourt MAO, Lima MCJS, Lima AK, Ortmann CF, et al. Phytochemical study and anti-inflammatory and antioxidant potential of Spondias mombin leaves. Rev Bras Farmacognosia. 2016;26(3):304-11. doi: 10.1016/j.bjp.2016.02.002.

 8. Gomes MS, Lins RDAU, Langassner SMZ, da Silveira EJD, de Carvalho TG, Lopes MLDS, et al. Anti-inflammatory and antioxidant activity of hydroethanolic extract of Spondias mombin leaf in an oral mucositis experimental model. Arch Oral Biol. 2020;111. PMID 104664.

 9. Cristofoli NL, Lima CAR, Vieira MMC, Andrade KS, Ferreira SRS. Antioxidant and antimicrobial potential of cajazeira leaves (Spondias mombin) extracts. Sep Sci Technol. 2019;54(4):580-90. doi: 10.1080/01496395.2018.1508233.

10. Simões EV. Spondias mombin L. In: Amaral ACF, Simões EV, Ferreira JLP. Coletânea científica de plantas de uso medicinal. Rio de Janeiro: Fiocruz; 2004. p. 165-185.

11. Mattieto RA, Matta VM. Cajá (Spondias mombin L.): [Açaí to citrus]. In: Yahia EM. Postharvest biology and technology of tropical and subtropical fruits. Vol. 2. Oxford, Cambridge, Philadelphia, New Delhi: Woodhead Publishing Limited; 2011. p. 330-53.

12. Tropicos.org [internet]. MO: Missouri Botanical Garden; c2021 [cited Jun 24 2021]. Available from: https://www.tropicos.org/name/1300270.

13. Clement CR. 1492 and the loss of Amazonian crop genetic resources. I. The relation between domestication and human population decline. Econ Bot. 1999;53(2):188-202. doi: 10.1007/BF02866498.

14. De Carvalho JEU, Alves RM. Recursos genéticos de espécies do táxon Spondias na Amazônia Oriental. In: Lederman IE, de Lira Júnior JF, da Silva Júnior JF, editors. Spondias no Brasil: umbu, cajá, e espécies afins. Recife: empresa pernambucana de pesquisa agropecuária, IPA/UFRPE; 2008. p. 69-74.

15. Do Sacramento CK, Souza FX. Cajá (Spondias mombin L.). Série frutas nativas, 4. Jabuticabal Funep. 2000.

16. Rios M. Nda S. Pastore Júnior F. Plantas da Amazônia. Vol. 450 espécies de uso geral. Brasília: Universidade de Brasília, Biblioteca Central; 2011.

17. World Agroforestry Centre. Agroforestree database [internet]. c2004 [cited Mar 04 2004]. Available from: https://www.worldagroforestry.org/output/suitability-key-central-american-agroforestry-species-under-future-climates-atlas.

18. Silva-Luz CL, Pirani JR, Pell SK, Mitchell JD. Flora do Brasil. Anacardiaceae [internet]. Rio de Janeiro: Instituto de Pesquisas Jardim Botânico do Rio de Janeiro; c2021 [cited Apr 21 2021]. Available from: http://floradobrasil.jbrj.gov.br/reflora/floradobrasil/FB4404.

19. Lorenzi H, Matos FJ. As Plantas medicinais no Brasil – nativas e exóticas. 2nd ed. São Paulo: Instituto Plantarum; 2008.

20. Prance GT, Silva MF, de Manaus Á. Manaus: INPA; 1975.

21. Plantas do Nordeste BR, Universitária, UFRN, editors. Especialmente do Ceará. 4^th ed. Fortaleza; 1960.

22. Lozano MB. Contribución al estudio de la anatomia floral y de la polinizacion del jobo (Spondias mombin L.). Caldasia. 1986;15:369-80.

23. Da Silva GA, de Brito NJN, dos Santos ECG, López JA, Almeida MG. Gênero Spondias: aspectos botânicos, composição química e potencial farmacológico. J biol Pharm agric Manag. 2014;10(01):27-41.

24. Justiniano MJ, Fredericksen TS. Nash D. Ecología y silvicultura de especies menos conocidas: azucaró Spondias mombin L., Anacardiaceae. 1st. ed. Santa Cruz: Bolfor; 2001.

25. Azevedo DdM, Mendes AMdS, Figueiredo AFd. Característica da germinação e morfologia do endocarpo e plântula de taperebá (Spondias mombin L.) – Anacardiaceae. Rev Bras Frutic. 2004;26(3):534-7. doi: 10.1590/S0100-29452004000300038.

26. Pizarro APB, et al. Avaliação morfoanatômica do caule primário de Spondias mombin L. I Congresso Sul Brasileiro de Plantas Medicinais, Maringá, PR. Vol. 013; 1999a.

27. Pizarro APB, et al. Avaliação morfológica e química das folhas da espécie Spondias mombin LINNAEU. [Anais da Iii reunião da Sociedade latino-americana de fitoquímica e IX Simpósio latino-americano de Farmacobotânica]. Vol. P15. Gramado, RS; 1999b.

28. Mattiero RdA, Lopes AS, Menezes HCd. Caracterização física e físico-química dos frutos da cajazeira (Spondias mombin L.) e de suas polpas obtidas por dois tipos de extrator. Braz J Food Technol. 2010;13(3):156-64. doi: 10.4260/BJFT2010130300021.

29. Abiodun OO, Nnoruka ME, Tijani RO. Phytochemical constituents, antioxidant activity, and toxicity assessment of the seed of Spondias mombin L. (Anacardiaceae). Turk J Pharm Sci. 2020;17(3):343-8. doi: 10.4274/tjps.galenos. 2020.38801, PMID 32636713.

30. Oladimeji AO, Aliyu MB, Ogundajo AL, Babatunde O, Adeniran OI, Balogun OS. Identification and comparison of the volatile constituents of fresh and dried leaves of Spondias mombin found in North-central Nigeria: in vitro evaluation of their cytotoxic and antioxidant activities. Pharm Biol. 2016;54(11):2674-8. doi: 10.1080/13880209.2016.1178308, PMID 27158981.

31. Lima TLC. Avaliação do potencial antiviral da Annona muricata (graviola) e Spondias mombin (cajá) contra o vírus dengue-2 em cultura de células [dissertation]. Natal: Federal University of Rio Grande do Norte; 2015.

32. Siqueira EMdS, Lima TLC, Boff L, Lima SGM, Lourenço EMG, Ferreira ÉG, et al. Antiviral potential of Spondias mombin L. leaves extract against herpes simplex virus type-1 replication using in vitro and in silico approaches. Planta Med. 2020;86(7):505-15. doi: 10.1055/a-1135-9066, PMID 32247285.

33. da Silva TSJ. Desenvolvimento e otimização do extrato padronizado de Spondias mombin (cajazeira): atividades anti-inflamatória e anti-herpes do extrato e da geraniina [dissertation]. Fortaleza: Federal University of Ceará; 2016.

34. Reed LJ, Muench H. A simple method of estimating fifty percent endpoints. Am J Hyg. 1938;27:493-7.

35. Ajao AO, Shonukan O, Femi-onadeko B. Antibacterial effect of aqueous and alcohol extracts of Spondias mombin, and Alchornea cordifolia - two local antimicrobial remedies. Int J Crude Drug Res. 1985;23(2):67-72. doi: 10.3109/13880208509069004.

36. Aromolaran O, Badejo OK. Efficacy of fresh leaf extracts of Spondias mombin against some clinical bacterial isolates from typhoid patients. Asian Pac J Trop Dis. 2014;4(6):442-6. doi: 10.1016/S2222-1808(14)60603-4.

37. Olugbuyiro JAO, Moody JO, Hamann MT. AntiMtb activity of triterpenoid-rich fractions from Spondias mombin L. Afr J Biotechnol. 2009;8(9):1807-9.

38. Accioly MP, Bevilaqua CML, Rondon FCM, De Morais SM, Machado LKA, et al. Leishmanicidal activity in vitro of Musa paradisiaca L. and Spondias mombin L. fractions. Vet Parasitol. 2012;187(1-2):79-84. doi: 10.1016/j.vetpar.2011.12.029, PMID 22521971.

39. Asomie J, Aina A, Owolo O, Olukanni O, Okojie D, Aina F, et al. Biogenic synthesis and characterization of silver nanoparticles from seed extract of Spondias mombin and screening of its antibacterial activity. Int J Nano Dimens. 2021;12(2):175-85.

40. Ajaegbu EE, Danga SPY, Chijoke IU, Okoye FBC. Mosquito adulticidal activity of the leaf extracts of Spondias mombin L. against Aedes aegypti L. and isolation of active principles. J Vector Borne Dis. 2016;53(1):17-22. PMID 27004574.

41. Brito SA, de Almeida CLF, de Santana TI, da Silva Oliveira AR, do Nascimento Figueiredo JCB, et al. Antiulcer Activity and Potential Mechanism of Action of the Leaves of Spondias mombin L Oxid Med Cell Longev. 2018;2018:1731459. doi: 10.1155/2018/1731459. PMID 29854075.

42. Sabiu S, Garuba T, Sunmonu T, Ajani E, Sulyman A, Nurain I, et al. Indomethacin-induced gastric ulceration in rats: protective roles of Spondias mombin and Ficus exasperata. Toxicol Rep. 2015;2:261-7. doi: 10.1016/j.toxrep.2015.01.002, PMID 28962358.

43. Adediwura F, Kio A. Antidiabetic activity of Spondias mombin extract in NIDDM rats. Pharm Biol. 2009;47(3):215-8. doi: 10.1080/13880200802462493.

44. Nworu CS, Akah PA, Okoli CO, Okoye TC. Oxytocic activity of leaf extract of Spondias mombin. Pharm Biol. 2007;45(5):366-71. doi: 10.1080/13880200701214755.

45. Uchendu CN, Isek T. Antifertility activity of aqueous ethanolic leaf extract of Spondias mombin (Anacardiaceae) in rats. Afr Health Sci. 2008;8(3):163-7. PMID 19357744.

46. Ademola IO, Fagbemi BO, Idowu SO. Anthelminthic activity of extracts of Spondias mombin against gastrointestinal nematodes of sheep: studies in vitro and in vivo. Trop Anim Health Pro. 2005;37:223-35.

47. Dos Santos Sampaio TI, de Melo NC, de Freitas Paiva BT, da Silva Aleluia GA, da Silva Neto FLP, da Silva HR, et al. Leaves of Spondias mombin L. a traditional anxiolytic and antidepressant: pharmacological evaluation on zebrafish (Danio rerio). J Ethnopharmacol. 2018;224:563-78. doi: 10.1016/j.jep.2018.05.037, PMID 29852265.

48. Maximino C, De Brito TM. Dias CAGM, Gouveia Jr A, Morato S. Scototaxis as anxiety-like behavior in fish. Nature. 2010;5(2):221-8.

49. Ayoka AO, Akomolafe RO, Iwalewa EO, Akanmu MA, Ukponmwan OE. Sedative, antiepileptic and antipsychotic effects of Spondias mombin L. (Anacardiaceae) in mice and rats. J Ethnopharmacol. 2006;103(2):166-75. doi: 10.1016/j. jep.2005.07.019, PMID 16188408.

50. Silva ELV. Estudo toxicológico não clínico do extrato hidroalcoólico de Spondias mombin L. [dissertation]. Recife: Federal University of Pernambuco; 2015.

51. Luz SMD. Atividade analgésica e toxicidade da Spondias mombin L. Em modelos animais [monography]. Campina Grande: State University of Paraíba; 2014.

52. Asuquo OR, Ekanem TB, Eluwa MA, Oko OO, Ikpi DE. Evaluation of toxicological effects of Spondias mombin in adult male Wistar rats. J Nat Sci Res. 2012;2(7):144-51.

53. Mousssa G, Alassane T, YaoEmile K, Jean-Baptiste ON’g, Mama K, Bernard DY, AngouePaul Y. Toxicity Assessment of an Aqueous Extract of the Stem Bark of Spondias mombin (Anacardiaceae) in Wistar albino rats. IntJCurrMicrobiolAppSci. 2018;7(1):3625-35. doi: 10.20546/ijcmas.2018.702.426.

54. Aulton ME, Taylor K. Aulton’s pharmaceutics: the design and manufacture of medicines. 5th ed. London: Elsevier Health Sciences; 2017.

55. Oiseoghaede JO, Oyawaluja AA, Odukoya OA, Ilomuanya MO, Yinusa OI, Raji OK. Formulation and Antioxidant Activity Evaluation of Spondias mombin - Abelmoschus esculentus Mucilage Emulsion. Bangla Pharma J. 2021;24(1):17-25. doi: 10.3329/bpj.v24i1.51631.

56. Guedes LM. Desenvolvimento, análise cinética e avaliação sensorial em humanos de formulação cosmética contendo polpa de cajá (Spondias mombin L.) [monography]. João Pessoa: Federal University of Paraíba; 2018.

57. Ramos e Silva J. Desenvolvimento e avaliação sensorial de formulação cosmética capilar contendo polpa de cajá (Spondias mombin l.) [monography]. João Pessoa: Federal University of Paraíba; 2018.

58. Tijani JO, Ugochukwu O, Fadipe LA, Bankole MT, Abdulkareem AS, Roos WD. One-step green synthesis of WO3 nanoparticles using Spondias mombin aqueous extract: effect of solution pH and calcination temperature. Appl Phys A. 2019;125:1-12.

59. Reshma HK, Avinash BS, Chaturmukha VS, Ashok RL, Jayanna HS. Hog plum (Spondias mombin) assisted ZnO nanoparticles synthesis: characterization and its impact on the performance of dye-sensitized solar cells. Mater Today Proc. 2021;37(2):434-9. doi: 10.1016/j.matpr.2020.05.424.

60. Le Cointe P. Árvores e plantas úteis (indígenas e aclimadas): nomes vernáculos e nomes vulgares, classificação botânica, habitat, principais aplicações e propriedades. 2nd ed A Amazonia Brasileira, 3. São Paulo: Companhia editora Nacional; 1947.

61. Delgado HS, Sifuentes TC, Herrera JEH, Ruiz JG, Chora EM, Davila MM, Isern FR. Plantas medicinales de la Amazônia peruana utilizadas por los curanderos, chamanes y herbolarios com fines antiinflamatórios. Iquitos: Instituto Peruano de Seguridad Social; 1998.

62. Estrella E. Plantas medicinales amazonicas: realidad y perspectivas. Lima: Texas Commission on the Arts; 1995.

63. Vieira LS. Fitoterapia da Amazônia: manual de plantas medicinais (a farmacia de Deus). 2nd ed. São Paulo: Agronomica Ceres; 1992.

64. Delgado HS, Sifuentes TC. Plantas medicinales del Jardin Botânico IMET-IPSS. Iquitos: Instituto Peruano de Seguridad Social; 1995.

65. Milliken W. Traditional anti-malarial medicine in Roraima, Brazil. Econ Bot. 1997;51(3):212-37. doi: 10.1007/BF02862091.

66. Roig MJT. Plantas medicinales, [Aromáticas e venenosas de Cuba]. Habana: Cultural; 1945.

67. Delgado HS, Herrera JEH, Sifuentes TC, Ruiz JG, Davila MM, Isern FR. Plantas medicinales de la Amazônia peruana utilizadas por curanderos y chamanes com fines anticonceptivos. Iquitos: Instituto Peruano de Seguridad Social; 1997.

68. Correa JEQ, Bernal HYM. Espécies vegetales promisorias de los paises del convenio Andrés Bello. Tomo I. Letra A. PREVECAB. Serie. Cien Tecnol. 1989;11. Bogota: Guadalupe.

69. Furtado LG, Souza RC, Van Den Berg ME. Notas sobre o uso terapêutico de plantas pela população cabocla de Marapanim. Bol. Mus. Para. Emilio Goeldi. 1978;70(1):1-31.

70. Revilla J. Plantas da Amazônia: oportunidades econômicas e sustentáveis. Manaus: INPA; 2001.

71. Luz FJF. Plantas medicinais de uso popular em Boa Vista, Roraima, Brasil. Hortic Bras. 2001;19(1):88-96. doi: 10.1590/S0102-05362001000100019.

72. Amorozo MCM, Gey A. Uso de plantas medicinais por caboclos do Baixo Amazonas. Barcarena, PA, Brasil. Bol. Mus. Para. Emilio Goeldi. 1988;4(1):47-131.

73. Akubue PI, Mittal GC, Aguwa CN. Preliminary pharmacological study of some Nigerian medicinal plants. 1. J Ethnopharmacol. 1983;8(1):53-63. doi: 10.1016/0378-8741(83)90089-2, PMID 6632937.

74. Matta AA. Flora médica brasiliense. 3rd ed. Serie Poranduba, 3. Manaus: Editora Valer; 2003.

75. Barbosa WC, de Nazare RFR, Hashimoto K. Estudo bromatológico e tecnológico da graviola e do tepereba. In: Encontro de Profissionais da química da amazônia. Vol. 1e 2; Anais.. São Luís: CRQ; 1981. p. 307-18.

76. Revilla J. Plantas úteis da Bacia Amazônica. Vol. 2. Manaus: INPA; 2002.

77. Matos FJA. Farmácias vivas: sistema de utilização de plantas medicinais projetado para pequenas comunidades. 3rd ed. Fortaleza: UFC; 1998.

78. Milliken W, Albert B. The use of medicinal plants by the Yanomami Indians of Brazil. Econ Bot. 1996;50(1):10-25. doi: 10.1007/BF02862108.

79. Villachica H. Frutales y hortalizas promissórios de la Amazônia. Lima: Texas Commission on the Arts; 1996.

80. ARde C. A. Cura pelas plantas e diversos meios de grande poder curativo. 3rd ed. São Paulo: Folco Masucci; 1972.

81. Guimarães EF, Rizzini CT, Mautone L, Mattos Filho AM. Árvores do Jardim Botânico do Rio de Janeiro. Rio de Janeiro: Jardim Botânico; 1993.

82. Rodrigues KF, Hesse M, Werner C. Antimicrobial activities of secondary metabolites produced by endophytic fungi from Spondias mombin. J Basic Microbiol. 2000;40(4):261-7. doi: 10.1002/1521-4028(200008)40:4<261:: AID-JOBM261>3.0.CO;2-D, PMID 10986672.

83. Rodrigues KF, Samuels GJ. Fungal endophytes of Spondias mombin leaves in Brazil. J Basic Microbiol. 1999;39:15-8.

84. Corthout J, Pieters L, Claeys M, Geerts St, Vanden Berghe DV, Vlietinck A. Antibacterial and molluscicidal phenolic acids from Spondias mombin. Planta Med. 1994;60(5):460-3. doi: 10.1055/s-2006-959532, PMID 7997478.

85. Sierra MN, Buchelli VF. Reproduction disorders in the mouse caused by Spondias mombin. Rev Colomb Cienc Quim Farm. 1986;15:63-70.

86. Junior S. Plantas exóticas. [Coleção edições do Pasquim]. Vol. 81. Rio de Janeiro: Codecri; 1981.

87. Corthout J, Pieters L, Claeys M, Berghe DV, Vlietinck A. Antiviral caffeoyl esters from Spondias mombin. Phytochemistry. 1992;31(6):1979-81. doi: 10.1016/0031-9422(92)80344-E.

88. Harbourne JB. Phytochemical methods: A guide to modern techniques of plant analysis. 2nd ed. London, New York: Chapman & Hall; 1984.

89. Trease GE, Evans WC. A textbook of pharmacognosy. 13th ed. London: Baulliere Tinall Ltd; 1989.

90. Persinos GJ, Quimby MW. Nigerian plants. 3. Phytochemical screening for alkaloids, saponins, and tannins. J Pharm Sci. 1967;56(11):1512-5. doi: 10.1002/jps.2600561129, PMID 6060599.

91. Wall ME, Eddy CR, McClennan ML, Klumpp ME. Detection and estimation of steroidal sapogenins in plant tissue. Anal Chem. 1952;24(8):1337-41. doi: 10.1021/ac60068a018.

92. Sofowora L. Medicinal plants and traditional medicine in Africa. Ibadan: Spectrum Books Ltd; 2013.