Stability and Antioxidant Activity of Pouteria macrophylla Fruit Extract, a Natural Source of Gallic Acid.

Pouteria macrophylla (cutite) fruits are rich in phenolic acids, resulting in antioxidant and skin depigmenting activity. The aim of this study, then, is to evaluate the cutite extract stability under three variations of light, time, and temperature using a Box-Behnken experimental design to analyze through the surface response the variations of the total phenolic content (TPC), antioxidant activity (AA), and gallic acid content (GA). A colorimetric assay was also performed, and a decrease in the darkening index was noticed due to the high phenolic coloration in the presence of light, indicating less degradation to extract stability. The experimental planning showed variations in all responses, and second-order polynomial models were calculated and considered predictable, as well as the effects were significant. The TPC exhibited a variation in less concentrated samples (0.5% p/v) at higher temperatures (90 °C). In contrast, the temperature was the only influential variable for AA, where only higher temperatures (60-90 °C) were able to destabilize the fruit extract. Differently, GA showed only the concentration as the influential variable, exhibiting that neither temperature nor time of exposure could affect the gallic acid content stability of P. macrophylla extract. For this, P. macrophylla extract was shown to be highly stable, providing a great perspective on cosmetic application.

Immunostimulant effects of diet supplementation with yellow (Pouteria campechiana), white (Casimiroa edulis), and black (Diospyros digyna) sapote nanocapsules on laying hens: in vitro and in vivo study.

Poultry is commonly infected by different bacteria and parasites in the environment, resulting in increased morbidity and mortality, but immunostimulants have been enhancing non-specific defense mechanisms conferring laying hens' protection. For this purpose, the pulp of yellow (Pouteria campechiana), white (Casimiroa edulis), and black (Diospyros digyna) sapotes were nanoencapsulated (YWB-SN) and evaluated in laying hens' peripheral blood leukocytes to test their addition to the experimental diets at a concentration of 0.5% (5g/kg of dry food) for 1 month (with two samples at days 15 and 30). The YWB-SN were safe when exposed to peripheral blood leukocytes (PBLs). The in vitro experiment showed that these nanocapsules enhanced reactive oxygen species production, and B-SN stimulated phagocytosis activity. Concerning the proinflammatory cytokine (TNF-α) transcription, this gene was upregulated after W-SN stimulation, while B-SN upregulated the IgG gene expression significantly. IgM was upregulated with any YBW-SN in PBLs after 24 h of stimulation. The in vivo study showed a notable B-SN immunostimulation in serum and an upregulation of TNF-α, IgM, and IgG mRNA transcription. Therefore, this study provides a new result of the yellow, white, and black sapote nanocapsules as a functional food for the poultry industry, highlighting the black sapote Diospyros digyna immunostimulant effect.

Pouteria macrophylla Fruit Extract Microemulsion for Cutaneous Depigmentation: Evaluation Using a 3D Pigmented Skin Model.

Here, we verify the depigmenting action of Pouteria macrophylla fruit extract (EXT), incorporate it into a safe topical microemulsion and assess its effectiveness in a 3D pigmented skin model. Melanocytes-B16F10- were used to assess the EXT effects on cell viability, melanin synthesis, and melanin synthesis-related gene transcription factor expression, which demonstrated a 32% and 50% reduction of intra and extracellular melanin content, respectively. The developed microemulsion was composed of Cremophor EL®/Span 80 4:1 (w/w), ethyl oleate, and pH 4.5 HEPES buffer and had an average droplet size of 40 nm (PdI 0.40 ± 0.07). Skin irritation test with reconstituted epidermis (Skin Ethic RHETM) showed that the formulation is non-irritating. Tyrosinase inhibition was maintained after skin permeation in vitro, in which microemulsion showed twice the inhibition of the conventional emulsion (20.7 ± 2.2% and 10.7 ± 2.4%, respectively). The depigmenting effect of the microemulsion was finally confirmed in a 3D culture model of pigmented skin, in which histological analysis showed a more pronounced effect than a commercial depigmenting formulation. In conclusion, the developed microemulsion is a promising safe formulation for the administration of cutite fruit extract, which showed remarkable depigmenting potential compared to a commercial formulation.

Green synthesis and characterization of titanium dioxide nanoparticles using leaf extract of Pouteria campechiana and larvicidal and pupicidal activity on Aedes aegypti.

The frequent application of synthetic insecticides creates resistance among insects, including mosquitoes, and causes environmental pollution and health issues. The current work aim at assessing the possibilities to produce and characterize the titanium dioxide (TiO2) nanoparticles (TiO2 NPs) mediated through the aqueous leaf extract of Pouteria campechiana, and their larvicidal and pupicidal activities against Aedes aegypti. The attained results showed that the aqueous leaf extract of P. campechiana had the efficiency to fabricate TiO2 NPs from TiO2. Under the UV-vis spectrum analysis, a sharp peak was recorded at 320 nm, which indicated the production of TiO2 NPs by the plant extract. The SEM analysis revealed that the synthesized TiO2 NPs were spherical, and 5 dissimilar diffractions were detected in the XRD spectrum analysis related to the TiO2 NPs. In FTIR analysis, a prominent peak was found at 1052.41 cm-1, corresponding to alcohol, and confirmed metal reduction. In the EDX analysis, there was a signal of around 58.44%, confirming the decrease in Ti from TiO2 NPs, and the remaining percentages were Ca, Al, and Mg. About 900 µg mL-1 of TiO2 NPs had excellent lethal activity against various larvae and pupa stages of Ae. aegypti. The attained results showed that the P. campechiana aqueous leaf extract could reduce TiO2 into TiO2 NPs and could be considered a mosquito control agent. Furthermore, this is the initial report about the aqueous leaf extract of P. campechiana effectively synthesizing the TiO2 NPs with anti-mosquito activity.

Pouteria lucuma Pulp and Skin: In Depth Chemical Profile and Evaluation of Antioxidant Activity.

Pouteria lucuma Ruiz and Pav., known as the 'Gold of the Incas' or 'lucuma', is a subtropical fruit belonging to the Sapotaceae family, with a very sweet flavor, used to prepare cakes, ice creams as well as in the baking and dairy industries. To date, the content of primary metabolites is known, but little information is reported about the composition in specialized metabolites. Moreover, no study is reported on skin which represent an important agricultural waste due to the high demand for lucuma. In order to have a preliminary metabolite profile of Pouteria lucuma, the extracts of pulp and skin have been analyzed by LC-ESI/LTQOrbitrap/MS/MS in negative ion mode. The careful analysis of the accurate masses, of the molecular formulas and of the ESI/MS spectra allowed to identify specialized metabolites belonging to phenolic, flavonoid and polar lipid classes. The LC-MS/MS analysis guided the isolation of compounds occurring in the pulp extract whose structures have been characterized by spectroscopic methods including 1D- and 2D-NMR experiments and ESI-MS analysis. Furthermore, the phenolic content of the extracts along with the antioxidant activity of extracts and isolated compounds was evaluated.

Isolation and identification of sapotexanthin 5,6-epoxide and 5,8-epoxide from red mamey (Pouteria sapota).

Two new carotenoids, sapotexanthin 5,6-epoxide and sapotexanthin 5,8-epoxide, have been isolated from the ripe fruits of red mamey (Pouteria sapota). Sapotexanthin 5,6-epoxide was also prepared by partial synthesis via epoxidation of sapotexanthin, and the (5R,6S) and (5S,6R) stereoisomers were identified by high-performance liquid chromatography-electronic circular dichroism (HPLC-ECD) analysis. Spectroscopic data of the natural and semisynthetic derivatives obtained by acid-catalyzed rearrangement of cryptocapsin 5,8-epoxide stereoisomers were compared for structural elucidation.

Pouteria ramiflora (Mart.) Radlk. extract: Flavonoids quantification and chemopreventive effect on HepG2 cells.

Pouteria ramiflora (Mart.) Radlk., popularly known as curriola, is commonly used in Brazil as medicinal plant to treat worm infections, dysentery, pain, inflammation, hyperlipidemia, and obesity. At present the safety of this extract when used therapeutically in human remains to be determined. Thus, the aim of this study was to examine cytotoxicity, antiproliferative, and antimutagenic actions of this extract. The hydroalcoholic extract from P. ramiflora leaves consisted of flavonoids identified and quantified as myricetin-3-O-ß-D-galactopyranoside (13.55 mg/g) and myricetin-3-O-α-L-rhamnopyranoside (9.61 mg/g). The extract exhibited cytotoxicity at concentrations higher than 1.5 µg/ml in human hepatocarcinoma (HepG2)and 2.5 µg/ml in non-tumoral primary gastric (GAS) cells using the MTT assay, and at concentrations higher than 3 µg/ml in HepG2 and 3.5 µg/ml in GAS cells by the neutral red assay. The extract did not show antiproliferative effect as evidenced by the nuclear division index (NDI). However, in the presence of benzo[a]pyrene (BaP) (positive control), an enhanced cytostatic effect in the NDI and flow cytometry was noted. It is of interest that when the extract was co-incubated with BaP a significant decrease in DNA damage was observed indicating an antimutagenic action. This protective effect might be attributed to myricetin and gallic acid found in P. ramiflora extract. The low cytotoxicity action and protective effect observed in the present study encourage further studies regarding other biological effects of P. ramiflora, as well as its potential use as a chemopreventive agent.

Antinociceptive and Antihyperalgesic Activity of a Traditional Maya Herbal Preparation Composed of Pouteria Campechiana, Chrysophyllum Cainito, Citrus Limonum, and Annona Muricata.

Preclinical Research The purpose of this work was to assess the antinociceptive and antihyperalgesic properties of an herbal preparation, composed of four vegetal species: Pouteria campechiana (P. campechiana), Chrysophyllum cainito (C. cainito), Citrus limonum (C. limonum), and Annona muricata (A. muricata), that is commonly used in combination (PCCA) in traditional Mayan medicine for the treatment of diabetes and pain. An ethanolic extract of PCCA was prepared at a ratio of 1:1:1:1 for each plant. The systemic antinociceptive effect of PCCA extract (50-600 mg/kg, p.o.) was dose-dependent in the rat formalin (1%) producing 66% antinociceptive response at 400 mg/kg, p.o. A concentration-dependent antinociceptive effect of the PCCA extract (20-160 mg/paw) was also demonstrated in the rat capsaicin (0.2%) test. The PCCA extract (100-400 mg/kg, p.o.) had antihyperalgesic effects in alloxan diabetic rats. These findings demonstrate the antinociceptive and antihyperalgesic effects of PCCA and supports the use of the plant extracts in Mayan folk medicine. Drug Dev Res 78 : 91-97, 2017. © 2017 Wiley Periodicals, Inc.

Activity of crude extracts from Brazilian cerrado plants against clinically relevant Candida species.

BACKGROUND: Medicinal plants have traditionally been used in many parts of the world as alternative medicine. Many extracts and essential oils isolated from plants have disclosed biological activity, justifying the investigation of their potential antimicrobial activity. In this study, the in vitro antifungal activity of six Brazilian Cerrado medicinal plant species were evaluated against clinically relevant Candida species. METHODS: The crude extract plants were evaluated against American Type Culture Collection (ATCC) standard strains of Candida spp. using disk diffusion method and determining the minimum inhibitory concentration (MIC). The chemical study results were confirmed by HPLC method. RESULTS: All six plant species showed antifungal activity. Among the species studied, Eugenia dysenterica and Pouteria ramiflora showed significant inhibitory activity against C. tropicalis at lowest MIC value of 125 and 500 µg/disc, respectively. The Eugenia dysenterica also disclosed MIC value of 125 µg/disc against C. famata, 250 µg/disc against C. krusei and 500 µg/disc against C. guilliermondii and C. parapsilosis. Pouteria torta, Bauhinia rufa, Erythroxylum daphnites and Erythroxylum subrotundum showed activity against the yeast strains with MIC value of 1000 µg/disc. The chemical study of the most bioactive extracts of Eugenia dysenterica and Pouteria ramiflora revealed catechin derivatives and flavonoids as main components. CONCLUSIONS: All six evaluated plant species showed good antifungal potential against several Candida strains. However, E .dysenterica and P. ramiflora showed the higher inhibitory effect against the non-albicans Candida species. Our results may contribute to the continuing search of new natural occurring products with antifungal activity.

Acute Toxicity and Dermal and Eye Irritation of the Aqueous and Hydroalcoholic Extracts of the Seeds of "Zapote" Pouteria mammosa (L.) Cronquist.

The common use of Pouteria mammosa (L.) Cronquist, "Mamey or Zapote," in food and ethnobotanic medicine shows its low or absent toxicity as fruit extracts prepared from seeds. However, it is essential to conduct security trials to scientifically support their use in drug therapy. This study evaluated the aqueous and hydroalcoholic extract (25%) Acute Oral Toxicity, obtained from the seeds of P. mammosa, in Sprague Dawley rats and dermal and eye irritability in New Zealand rabbits. The 404 and 405 acute dermal and eye irritation/corrosion guidelines were used, as well as the 423 Acute Oral Toxicity guideline, Acute Toxic Class Method of the Organization for Economic Cooperation and Development (OECD). The aqueous extract was located in the following category: not classified as toxic (CTA 5), while hydroalcoholic extract at 25% was classified as dangerous (CTA 4). Both extracts can be used without side reaction that irritates the skin which permitted classification as potentially not irritant. P. mammosa in the two extracts caused mild and reversible eye irritation, and it was classified as slightly irritating.

Development of a Large Set of Microsatellite Markers in Zapote Mamey (Pouteria sapota (Jacq.) H.E. Moore & Stearn) and Their Potential Use in the Study of the Species.

Pouteria sapota is known for its edible fruits that contain unique carotenoids, as well as for its fungitoxic, anti-inflammatory and anti-oxidant activity. However, its genetics is mostly unknown, including aspects about its genetic diversity and domestication process. We did high-throughput sequencing of microsatellite-enriched libraries of P. sapota, generated 5223 contig DNA sequences, 1.8 Mbp, developed 368 microsatellites markers and tested them on 29 individuals from 10 populations (seven wild, three cultivated) from Mexico, its putative domestication center. Gene ontology BLAST analysis of the DNA sequences containing microsatellites showed potential association to physiological functions. Genetic diversity was slightly higher in cultivated than in the wild gene pool (HE = 0.41 and HE = 0.35, respectively), although modified Garza-Williamson Index and Bottleneck software showed evidence for a reduction in genetic diversity for the cultivated one. Neighbor Joining, 3D Principal Coordinates Analysis and assignment tests grouped most individuals according to their geographic origin but no clear separation was observed between wild or cultivated gene pools due to, perhaps, the existence of several admixed populations. The developed microsatellites have a great potential in genetic population and domestication studies of P. sapota but additional sampling will be necessary to better understand how the domestication process has impacted the genetic diversity of this fruit crop.

Cryptocapsinepoxide-type carotenoids from red mamey, Pouteria sapota.

New carotenoids, cryptocapsin-5,6-epoxide, 3'-deoxycapsanthin-5,6-epoxide, and cryptocapsin-5,8-epoxides, have been isolated from the ripe fruits of red mamey (Pouteria sapota). Cryptocapsin-5,6-epoxide was prepared by partial synthesis via epoxidation of cryptocapsin, and the (5R,6S)- and (5S,6R)-stereoisomers were identified by HPLC-ECD analysis. Spectroscopic data of the natural (anti) and semisynthetic (syn) derivatives obtained by acid-catalyzed rearrangement of cryptocapsin-5,8-epoxide stereoisomers were compared for structural elucidation. Chiral HPLC separation of natural and semisynthetic samples of cryptocapsin-5,8-epoxides was performed, and HPLC-ECD analysis allowed configurational assignment of the separated stereoisomers.

Neuroprotective effects of Pouteria ramiflora (Mart.) Radlk (Sapotaceae) extract on the brains of rats with streptozotocin-induced diabetes.

Diabetes mellitus is a chronic disease involving persistent hyperglycemia, which causes an imbalance between reactive oxygen species and antioxidant enzymes and results in damage to various tissues, including the brain. Many societies have traditionally employed medicinal plants to control the hyperglycemia. Pouteria ramiflora, a species occurring in the savanna biome of the Cerrado (Brazil) has been studied because of its possible ability to inhibit carbohydrate digestion. Rats with streptozotocin-induced diabetes treated with an alcoholic extract of Pouteria ramiflora show an improved glycemic level, increased glutathione peroxidase activity, decreased superoxide dismutase activity, and reduced lipid peroxidation and antioxidant status. The extract also restored myosin-Va expression and the nuclear diameters of pyramidal neurons of the CA3 subregion and that of the polymorphic cells of the hilus. We conclude that Pouteria ramiflora extract exerts a neuroprotective effect against oxidative damage and myosin-Va expression and is able to prevent hippocampal neuronal loss in the CA3 and hilus subfields of diabetic rats. However, future studies are needed to understand the mechanism of action of Pouteria ramiflora extract in acute and chronic diabetes.

Pouteria ramiflora extract inhibits salivary amylolytic activity and decreases glycemic level in mice.

In this study, extracts of plant species from the Cerrado biome were assessed in order to find potential inhibitors of human salivary alpha-amylase. The plants were collected and extracts were obtained from leaves, bark, and roots. We performed a preliminary phytochemical analysis and a screening for salivar alpha-amylase inhibitory activity. Only three botanical families (Sapotaceae, Sapindaceae and Flacourtiaceae) and 16 extracts showed a substantial inhibition (>75%) of alpha-amylase. The ethanolic extracts of Pouteria ramiflora obtained from stem barks and root barks decreased amylolytic activity above 95% at a final concentration of 20 µg/mL. Thus, adult male Swiss mice were treated orally with P. ramiflora in acute toxicity and glycemic control studies. Daily administration with 25, 50 and 100 mg/kg of aqueous extract of P. ramiflora for eight days can reduce significantly body weight and blood glucose level in mice. These data suggest that the crude polar extract of P. ramiflora decreases salivary amylolytic activity while lowering the blood levels of glucose.

Pouteria spp. fruits: Health benefits of bioactive compounds and their potential for the food industry.

The Sapotaceae family encompasses the genus Pouteria spp., comprising approximately 1,250 species of fruits cherished by consumers for their delightful assortment and flavors. Over the years, extensive research has been devoted to exploring the natural bioactive compounds present in these fruits, with the primary goal of preventing and/or mitigating the risk of degenerative diseases. Despite their widespread popularity in numerous countries, the chemistry, nutritional content, and biological potential of these fruits remain relatively unexplored. This comprehensive review aims to shed light on the principal volatile and non-volatile chemical components found in Pouteria fruits, which present notable antioxidant properties. By doing so, a broad perspective on the current trends in characterizing these compounds and their potential applications were provided, as well as the associated health benefits. Additionally, the prospects and potential applications of Pouteria fruits in the food industry were explored herein.

Inhibitory activity of α-amylase and α-glucosidase by plant extracts from the Brazilian cerrado.

Diabetes mellitus is the most common disease in the world. One therapeutic approach for treating diabetes is inhibition of α-amylase and α-glucosidase activities to reduce postprandial blood glucose levels. In vitro tests showed that several plant extracts from Brazilian cerrado species can inhibit the activity of α-amylase and α-glucosidase. The extracts of Eugenia dysenterica, Stryphnodendron adstringens, Pouteria caimito, Pouteria ramiflora, and Pouteria torta showed strong α-amylase and α-glucosidase inhibitory activity. Eugenia dysenterica, P. caimito, P. ramiflora, and P. torta aqueous extracts exerted the highest activity against α-amylase (IC50) values of 14.93, 13.6, 7.08, and 5.67 µg/mL, respectively) and α-glucosidase (IC50 values of 0.46, 2.58, 0.35, and 0.22 µg/mL, respectively). Stryphnodendron adstringens ethanol extract also exhibited inhibitory activity against both enzymes (IC50) 1.86 µg/mL against α-amylase and 0.61 µg/mL against α-glucosidase). The results suggest that the activity of these cerrado plants on α-amylase and α-glucosidase represents a potential tool for development of new strategies for treatment of diabetes.

Pouteria sapota (Red Mamey Fruit): Chemistry and Biological Activity of Carotenoids.

BACKGROUND: Red mamey is the fruit of P. sapota, a tree found in Mesoamerica and Asia. This fruit is considered a nutraceutical due to its multiple beneficial health including antiamyloidogenic activity and potential anti-tumorigenic property. Red mamey contain a variety of carotenoids including novel ketocarotenoids such as sapotexanthin and cryptocapsin. A ketocarotenoid is a chemical compound with a carbonyl group present in the ß-ring or in the double bond chain of a carotenoid. In red mamey, the 3'-deoxy-k-end group in sapotexanthin has proven to be an important pro-vitamin A source, which is essential for maintaining a healthy vision and cognitive processes. OBJECTIVE: This work reviews the current knowledge about the chemistry and biological activities of carotenoids in red mamey. METHOD: An exhaustive extraction is the most usual methodology to isolate and thoroughly characterize the carotenoids present in this fruit. High performance liquid chromatography is used to determine the profile of total carotenoids and its purity, while atmospheric pressure chemical ionization was used to determine their molecular weight and nuclear magnetic resonance determined their structure. RESULT: For each 100 g of fresh weight, 0.12 mg of total carotenoid from this fruit can be obtained. Out of the more than 47 reported carotenoids in red mamey, only 34 have a detailed characterization. CONCLUSION: It is important to continue studying the chemical composition and biological activity of this unique tropical fruit with commercial and nutritional value.

Vitamin A- and C-rich Pouteria camito fruit derived superparamagnetic nanoparticles synthesis, characterization, and their cytotoxicity.

Background: Recently, green nanoparticles are gaining importance in drug development because of their lower toxicity, sustainability, cost effectiveness, simplicity, and ecofriendly nature compared with toxic chemicals. Objective: In this study, we developed a nontoxic method for synthesizing iron oxide nanoparticles by using the fruit of Pouteria caimito that is rich in vitamin A and C and evaluated their cytotoxicity. Methods: Pouteria caimito fruit¬-derived superparamagnetic nanoparticles (PCSNs) were characterized using physical and chemical methods, and their cytotoxicity was examined using the 3-(4, 5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide (MTT) assay. Results: Ultraviolet-visible spectroscopy (UV-Vis spectro) analysis of PSNs showed a peak at 277 nm. Transmission electron microscopy (TEM) findings showed that PSNs exhibited a nanorod shape with their sizes ranging from 9.41 nm to 16.96 nm (average size: 13.08 nm). The findings of dynamic light scattering (DLS) indicated that the particle size was 186. 6-847.3 d.nm with an average of 367.5 d.nm. The Zeta potential analysis indicated that PSNs exhibited uniform surface charge distribution, and their surface charge was equal to -13.7 mV. Fourier-transform infrared spectroscopy (FTIR) analysis showed that PSNs exhibited bands at 3412, 1629, 1384, 1075, 818, 697, and 471 cm-1. Energy-dispersive X-ray spectroscopy (EDX) results showed that iron was the major element present in PCSNs, followed by other biomolecules such as C, O, and Cl, indicating the production of iron oxide nanoparticles. Conclusion: The Pouteria caimito fruit that possesses strong oxidizing and nontoxic properties can be a potentially attractive source for the production of iron oxide nanoparticles. Moreover, the cytotoxicity assay results revealed that iron oxide nanoparticles synthesized using the Pouteria caimito fruit extract derived can be used for targeting cancer cells and treating other diseases because of their nontoxic nature. These nanoparticles can be used for the treatment of cancer and other diseases in the future.

Sapotexanthin, an A-provitamin carotenoid from red mamey (Pouteria sapota).

From the ripe fruits of red mamey (Pouteria sapota) sapotexanthin, a new carotenoid, was identified as (all-E,5'R)-ß,κ-caroten-6'-one.

Pouteria ramiflora leaf extract on emulgel in wound healing activity in diabetic rats.

The genus Pouteria has been studied because it presents various activities, among which is its anti-inflammatory potential. The effects of Pouteria ramiflora Carbopol gel on the healing of skin wounds in diabetic rats were evaluated by microscopic imaging. Streptozotocin was administered intraperitoneally in animals that had fasted for 12 hours, a situation confirmed by the glycemic index (˃ 240 mg dL-1). An excision on the back of the animals was performed and three groups were formed: Control (Gel), Ethanolic extract (Ext) and Gel + extract 2% (Ext+gel); the histopathological evaluation occurred on the 7th, 14th, 21st and 30th days after the post-operative period. The results of the phytochemical prospecting of P. ramiflora extract demonstrated the major presence of phenolic compounds and flavonoids; the assessment of the inflammatory infiltrate on the 7th day was higher on group Ext and Ext+gel when compared to group Control; on the 14th day control and Ext (p<0.05). The quantification of fibroblasts was higher on the 7th day among the three treatments, control and Ext (p<0.05), on the 21st day. Angiogenesis showed a higher number of vessels in Ext+gel group (p<0.05) on the 7th day; in Control, Ext and Ext+gel (p<0.05) on the 14th day; and Control and Ext (p<0.05)on the 21st day. The histopathological results showed that the formulation Ext+gel was efficient in tissue reparation and decrease in inflammatory cells on the diabetic's animals.