Duguetia furfuracea, popularly known as “araticum-seco,” is traditionally used in folk medicine for the treatment of pain and inflammatory disorders. This study aimed to analyze the chemical composition and investigate the anti-inflammatory and antinociceptive activities of the alkaloid fraction obtained from the leaves of D. furfuracea (DfFAlk). The chemical composition of DfFAlk was characterized using ultra-fast liquid chromatography (UFLC) coupled with mass spectrometry (UFLC/ESI). In vivo anti-inflammatory activity was assessed using the carrageenan-induced paw oedema model. The effects of DfFAlk on polymorphonuclear leukocyte recruitment and tumor necrosis factor alpha (TNF-α) levels were also evaluated in mouse footpads. In addition, the antinociceptive effect was investigated using the abdominal writhing test, formalin test, and thermal hyperalgesia models, and motor and balance performance were assessed using the rota-rod test. Thirty-four alkaloids were annotated belonging to the aporphine, tetrahydroprotoberberine, benzyltetrahydroisoquinoline, tetrahydroisoquinoline, (bis)benzyltetrahydroisoquinoline, and proaporphine classes. Oral treatment with DfFAlk (100 and 300 mg/kg) significantly inhibited paw oedema, from 2 to 6 h post inflammatory stimulus. The alkaloid fraction (300 mg/kg) attenuated the tissue inflammatory infiltrate 4 and 6 h after carrageenan injection, and decreased TNF-α production, 4 h post carrageenan. The fraction (300 mg/kg) also significantly attenuated the acetic acid-induced writhing response and the formalin-induced licking in both phases. Furthermore, in the hot-plate model, the DfFAlk (300 mg/kg) increased the latency to response from 1 to 3 h after oral treatment. Additionally, DfFAlk-treated mice did not show any alteration of motor and balance performances. The data indicate that DfFAlk has anti-inflammatory and antinociceptive activities.

ABSTRACT Purpose: To evaluate the topical treatment with the ethanolic extract of Ocimum basilicum L. (OBEE) on excisional wounds in mice. Methods: The plant material was identified and collected, and the ethanolic extract was obtained from the aerial parts of O. basilicum. The OBEE was resuspended in saline at concentrations of 38 and 100 mg/kg for topical application on the left and right lesions, respectively. Mice were anesthetized, excisional wounds were made on the dorsal region and divided into four groups (n = 6) based on treatment duration: one, three, five, and 21 days. The control group received saline. After the treatments, the animals were euthanized, and the wounds were collected for histopathological analysis the inflammatory infiltrate, mast cell count, and deposition of newly synthesized collagen matrix. Results: The daily topical application of OBEE at concentrations of 38 and 100 mg/kg reduced the inflammatory response, evidenced by decreased leukocyte infiltration in the damaged tissue, and improved the deposition of newly synthesized matrix, with thicker, more intertwined collagen fibers resembling intact skin. These effects may be attributed to the phenolic compounds, tannins, flavonoids, and essential oils present in basil. Conclusion: OBEE shows promise as a potential healing agent in excisional wounds.

ABSTRACT Purpose: To evaluate the effect of the topical application of the ethanol extract (EESL) and the hydroethanolic fraction (HFSL) of ripe Solanum lycocarpum fruit on the healing of experimentally-induced wounds in mice. Methods: The EESL and HFSL obtained from ripe fruit of the species S. lycocarpum were obtained by percolation with ethanol. They were tested in the healing of excisional wounds in mice, which were induced in anesthetized animals using a 7-mm dermatological punch. They were divided according to the treatment period and group, n = 6, and received topical application of the EESL or HFSL daily or saline solution for one, five, seven, or 21 days. At the end of this period, the animals were euthanized, and the lesions were subjected to histopathological processing and analysis to evaluate macroscopic area of the wound and microscopic analysis by morphometry of the number of leukocytes, mast cells, fibroblasts, re-epithelialization, and matrix deposition. Results: The application of the EESL and HFSL reduced the number of leukocytes after one, five, and seven days of treatment. EESL improved re-epithelialization and tissue proliferation in wound healing from day 7. Conclusion: The study demonstrated that daily administration of EESL and HFSL exhibit wound healing activity, with this effect being more pronounced by EESL. To our knowledge, this is the first report of the anti-inflammatory and healing activity of this species through topical application.

Celtis iguanaea, widely used in Brazilian folk medicine, is known for its analgesic and anti-inflammatory properties. This study evaluated the in vitro antioxidant capacity and the in vivo antinociceptive and anti-inflammatory mechanisms of the standardized spray-dried Celtis iguanaea hydroethanolic leaf extract (SDCi). Phytochemical analysis showed that SDCi contains 21.78 ± 0.82 mg/g polyphenols, 49.69 ± 0.57 mg/g flavonoids, and 518.81 ± 18.02 mg/g phytosterols. UFLC-DAD-MS identified iridoid glycosides, p-coumaric acid glycosides, flavones, and unsaturated fatty acids. Antioxidant assays revealed an IC50 of 301.6 ± 38.8 µg/mL for DPPH scavenging and an electrochemical index of 6.1 μA/V. In vivo, SDCi (100–1000 mg/kg, p.o) did not impair locomotor function (rotarod test) but significantly reduced acetic acid-induced abdominal writhing and both phases of the formalin test at higher doses (300 and 1000 mg/kg). The antinociceptive effects were independent of α-2 adrenergic receptors. SDCi also increased latency in the hot-plate test and reduced paw edema in the carrageenan model, accompanied by decreased IL-1β and increased IL-10 levels. Histological analysis showed a 50% reduction in inflammatory cell infiltration. These findings support SDCi as an effective anti-inflammatory and antinociceptive phytopharmaceutical intermediate, with potential applications in managing pain and inflammation.

Purpose: This study aimed to evaluate the therapeutic effect of an ethanol extract of Ocimum basilicum L. (EEOb) aerial parts against Ehrlich's experimental tumor (EET) in mice. Methods: Swiss mice were divided into two groups (control and treated; n = 6). On day 21, all mice were inoculated subcutaneously with 2 × 106 (0.05 mL) EET cells in the left paw for solid tumor development. This study lasted 28 days. Treatment began 24 hours after inoculation with EET. Measurements of dorsoplantar thickness were used to assess tumor growth. The paw pad was collected for histopathological analysis and stained using the argyrophilic nucleolar organizing regions (AgNOR) technique and immunohistochemistry for proliferating cell nuclear antigen, Bcl-2 and Bax. Results: The treatment of animals with EEOb at 100 mg/kg intraperitoneally was able to reduce the growth (Control = 3.7 ± 0.1 mm vs. EEOb = 5.7 ± 0.2 mm) and the number of AgNORs of solid Ehrlich tumor. The antitumor effect of EEOb was associated with the induction of apoptosis of tumoral cell, as suggested by the reduction of the content of Bcl-2 induced by extract. Conclusions: The study demonstrated that daily administration of EEOb is able to reduce the growth of EET by induce apoptosis of tumoral cells.

Ovarian puncture has been widely used in assisted reproduction, but there are still gaps about its effects on ovarian morphophysiology, as well as the relationship between inflammation caused by this procedure and the follicular growth and fertility. The aim of this study was to investigate the effects of ovarian puncture on folliculogenesis and fertility. Mice (n = 24) were divided into two groups: (1) SHAM—both ovaries were exposed and repositioned and (2) Punctured—ovaries were exposed, punctured, and repositioned. After 96 h of surgery, ovaries were collected for morphofunctional analysis. New females were used for the superovulation (n = 10) and fertility assays (n = 10). Increased volumetric density of inflammatory cells—p = 0.0005, p = 0.0013; hemorrhagic foci—p < 0.0001; and inflammatory exudate—p < 0.0001 could be noticed on the punctured group, compared to SHAM. The percentage of primordial follicles was lower on the punctured ovaries (p = 0.00294). Ovarian puncture has also induced an increase in the proliferation of granulosa cells of primary (p = 0.0321) and antral follicles (p = 0.0395), and an increased apoptotic index of antral follicles (p = 0.0100). There was no influence on expression of some genes related to inflammation, collagen deposition and folliculogenesis progression. The reproductive aspects (oocyte retrieval and number of fetuses per female) were not altered (p > 0.05). Taken together, our findings strongly suggest that ovarian puncture results in a local inflammation that affects follicular growth and atresia. However, it does not affect female fertility, which strengthens the safety of this procedure.

Maintaining the structural and functional integrity of the skin is critical to ensure body homeostasis. After damage, a series of cellular and molecular events occurs in this structure in order to repair the injured tissue. Imbalances in one or more repair steps are commonly related to difficulties in proceeding with healing. This has driven the search for natural molecules from plants to improve the repair process that is economical with less side effects. In this context, the common medicinal herb, Ocimum basilicum L., used globally from cooking to practices in folk medicine, has in its phytoconstitution substances with different actions such as anti-inflammatory, antioxidant, antimicrobial. Therefore, in the present study, we have evaluated the anti-inflammatory effect of intraperitoneal treatment with ethanolic extract of O. basilicum (EEOB) on wound healing in mice. Incisional wounds were induced in mice, they were divided according to treatment period and group, n=6, and received EEOB intraperitoneally (i.p.) at 150 mg/kg daily or saline solution for 5 or 7 days. At the end of this period, the animals were euthanized and the lesions underwent histopathological processing and analysis. In animals treated with EEOB injection, there was a decrease in the number of leukocytes at 5 days and mast cells at 7 days post-injury compared to the control. The observed anti-inflammatory action can be attributed to the phenolic compounds and their individual or synergistic effects on the healing process.

Role of mast cells in various phases of skin wound healing is well reported in literature. However, there is much controversy about the importance of mast cells in skin wound repair. Few studies have demonstrated the presence of mast cells in skin wound repair in middle-aged and senescent individuals. The mast cells are resident cells in the skin and participate in the inflammatory process and wound repair response. It is known that there are major changes in the immune system with aging, including in the skin. In this work, we evaluated the density and maturation of mast cells (mature, intermediate and immature) at the edges of skin wounds in young, middle-aged and senescent mice by toluidine blue and alcianine-safranin blue staining. We found that there is a significant decrease in mast cells in senescent mice. There is a predominance of immature mast cells at all ages 5 days after injury. But the data are intriguing, as in senescent mice there are fewer mature mast cells. Further studies should be carried out to understand the role of mast cells during aging.

ETHNOPHARMACOLOGICAL RELEVANCE:Solanum lycocarpum A. St. Hil. (Solanaceae) is a species from the Brazilian Cerrado, exhibiting several medicinal properties, being used by the population in the treatment of ulcers, bronchitis, asthma and hepatitis, which involve inflammatory processes. AIM OF THIS STUDY:This study aimed to chemically characterize the dichloromethane fraction (DCM), as well as verify its antinociceptive, anti-inflammatory and antioxidant potential. MATERIALS AND METHODS:The DCM fraction was obtained by partitioning the ethanol extract. The chemical constituents of the DCM fraction were characterized by LC-DAD-MS. The DPPH and FRAP assays were used to evaluate the antioxidant potential. The carrageenan-induced paw edema model was used to assess the anti-inflammatory effects, and the inflammatory infiltrate was evaluated by qualitative and quantitative histological analyses. The antinociceptive action of the DCM fraction was evaluated by acetic acid-induced abdominal writhing test, formalin-induced nociception and hot-plate test. RESULTS:Steroidal alkaloids solasonine, solasodine and solamargine, as well as the alkaloid peiminine/imperialine and caffeoylquinic acids, were annotated in DCM fraction by LC-DAD-MS. The DCM fraction showed antioxidative action in the in vitro DPPH and FRAP tests, as well as an anti-inflammatory effect for the three evaluated doses of 30, 100 and 300 mg/kg in the fourth and sixth hours after the administration of carrageenan. The histological analyses evidenced considerably reduction in leukocyte migration and the number of polymorphonuclear leukocytes. The study also demonstrated antinociceptive activity for the DCM fraction, which reduced abdominal writhing at three concentrations evaluated, as well as a decrease in paw licking in the formalin-induced nociception test both in the neurogenic phase and the inflammatory phase, with greater effectiveness compared to the anti-inflammatory indomethacin. The DCM fraction also increased the latency time of the animals in the hot plate test 60 min after treatment, although it did not seem to involve the opioidergic system. CONCLUSION:This work evidenced that the dichloromethane fraction of S. lycocarpum fruit possesses antinociceptive and anti-inflammatory potential, which supports its use in folk medicine for management inflammatory conditions.

Introduction:In order to develop interprofessionality, it is necessary to rebuild relationships in teamwork, with regard to creating specific conditions so that the team does not remain just as a set of subjects.Interprofessional Education (IPE) in health is one of the main strategies to train professionals.The "PET-Saúde Interprofissionalidade" of the Federal University of São João del-Rei (UFSJ) was the result of these strategies, aiming to promote of IPE, through initiatives that integrate the knowledge of different professions, promoting collaborative work.Objective: The purpose of this study was to evaluate the interprofessional work carried out by the managers of Family Health Strategies (FSH) in the city of São João del-Rei/MG/Brazil and to observe how this condition affects the school-service relationship.Methods: This is a qualitative research, in which 16 semi-structured interviews were made with managers in São João del-Rei/MG.Results and discussion: It was noted that there is confusion between the concepts of multiprofessionality, interdisciplinarity and interprofessionality.There were many referrals of cases between specialties, which is not configured as a shared and collaborative action of teamwork.Even so, managers, without knowledge of the concept of interprofessionality, saw the importance of an integrated approach to patients in more complex cases.Conclusion: It was clarified that the teaching-service relationship is an opportunity to implement interprofessionality.The managers' FHS of São João del-Rei were not aware of the concept of interprofessionality, often confused with interdisciplinarity and multiprofessionality, although they adopted collaborative practices in their work routine.

A 4-hidroxicumarina (4H) é um composto fenólico natural e sintético que apresenta atributos importantes, incluindo propriedades anti-HIV, antitumoral e anticoagulante. Considerando suas importantes atividades biológicas e a utilização da 4H, o objetivo do presente estudo foi investigar as atividades tóxica, mutagênica, antimutagênica e antioxidante da 4H, obtido comercialmente, em experimentos in vivo e in vitro. Os efeitos da administração oral aguda na dose de 200 mg / kg de 4H foram investigados pela triagem hipocrática em animais. O ensaio de micronúcleo em sangue periférico e o teste de Ames foram utilizados para análise de mutagenicidade, enquanto a antimutagenicidade foi testada contra a ciclofosfamida também pelo ensaio de micronúcleo in vivo. Para todos os testes in vivo foram utilizados camundongos Swiss. A atividade antioxidante foi determinada pela capacidade da amostra 4H de sequestrar o radical estável 2,2-difenil-1-picrilhidrazil (DPPH). Os resultados mostraram que o 4H não induziu alterações no comportamento ou na histologia dos animais tratados nem na atividade mutagênica (gênica ou cromossômica). Por outro lado, exibiu efeito protetor contra ciclofosfamida e potencial antioxidante. A 4H é amplamente utilizada clinicamente como uma molécula precursora na síntese de fármacos anticoagulantes sintéticos. Portanto, os resultados obtidos são de extrema importância, pois demonstram ausência de potencial mutagênico e proteção contra danos cromossômicos.

Studies have demonstrated the beneficial effects of light- and moderate-intensity physical exercise on the nervous system of animals with cerebral ischemia. To investigate the effects of two high-intensity physical exercise protocols, standardized for resistance and strength gain, in rats trained before cerebral ischemia induced by Bilateral Common Carotid Artery Occlusion (BCCAO). Forty-eight male Wistar rats were divided into two groups: with ischemia and without ischemia (sham). Both groups were subdivided into animals that performed high-intensity exercises in the muscle strength modality (I+Ex2; Sham+Ex2; n=16); animals submitted to high-intensity exercises in the aerobic modality (I+Ex1; Sham+Ex1; n=16), and animals that did not practice physical exercises - sedentary (I+Sed; Sham+Sed, n=16). Cerebral ischemia was induced using the BCCAO model. The physical training program used before the procedure was of high intensity, in the aerobic and muscular strength modalities, and was performed using a vertical ladder, for 4 weeks, 5 days per week. In order to process and stain the brain tissue, the Nissl method was used for neuron labeling and quantification in the cortex, striatum, and hippocampus. As for the animals' body weight and the heart weight differences were found between the groups I+Ex2 and Sham+Ex2 (p<0.05). Data on neuron quantification in the cerebral cortex, dentate gyrus, and right and left striatum revealed significant differences between groups. High-intensity physical training in the strength gain modality promotes significant damage to the animal's brain when performed prior to BCCAO-induced cerebral ischemia.

ETHNOPHARMACOLOGICAL RELEVANCE:Solanum lycocarpum St. Hil. (Solanaceae) is widely distributed in the Brazilian Cerrado and is used in folk medicine for treatment of inflammatory disorders, such as asthma and hepatitis, as weel as antirheumatic. AIM OF THE STUDY:The aims of this study were to evaluate the antioxidant, anti-inflammatory and antinociceptive activities of the ethanol extract (EE) obtained from the ripe fruits of S. lycocarpum and to identify its chemical constituents. MATERIALS AND METHODS:The extract was obtained by percolation with ethanol. This extract was analyzed by liquid chromatography coupled to a diode array detector and mass spectrometer (LC-DAD-MS) for identify its chemical constituents. The antioxidant activity was determined by the reaction with 1,1-diphenyl-2-picrylhydrazyl radical (DPPH). In vivo anti-inflammatory potential was assessed using carrageenan-induced paw edema model, while qualitative and quantitative histological analyses evaluated of the inflammatory infiltrate at different times and treatments. The antinociceptive effect of the EE was evaluated by acetic acid-induced abdominal writhing test, formalin-induced nociception and hot-plate test. RESULTS:The main compounds identified in EE were steroidal glycoalkaloids (such as robeneoside B or hydroxysolasonine isomers and solanandaine isomers), the aglycone alkaloids peiminine and solasodine, di- and tri-O-caffeoylquinic acid derivatives, O-coumaroyl caffeoylquinic acid derivatives, N1,N10-bis-(dihydrocaffeoyl)spermidine, di-O-hexoside, and hexonic acid. In addition, the EE showed significant antioxidant activity. Intraperitoneal (i.p.) treatment with EE (300 mg/kg) exhibited anti-inflammatory activity. Qualitative and quantitative histological analyses showed that EE significantly reduced the cell infiltrate in acute inflammation. The EE, in all doses evaluated, significantly reduced the abdominal contortions in mice. Besides, reduced licking time was found in both phases in the formalin test after treatment with EE (100 and 300 mg/kg). In addition, the opioid receptor antagonist naloxone reversed the antinociceptive activity of morphine in the both phases the test, but it did not reverse the antinociceptive activity of the EE. The EE (300 mg/kg) also caused an increase in the latency to response in the hot-plate test. CONCLUSION:The ripe fruits of S. lycocarpum exhibit antioxidant, anti-inflammatory, and antinociceptive activities, attributed mainly to the presence of alkaloids, such as solasodine and peiminine, as well as caffeoylquinic acids in their chemical composition. These results contribute to use of S. lycocarpum ripe fruits for the treatment of inflammatory and painful process.

Brain ischemia is the second most deadly disease in the world and it has already been proven that mild and moderate physical exercises minimize the deleterious effects of this disease on the brain. Curcumin has also been considered a neuroprotective substance. Therefore, the goal of this study was to evaluate the effects of high-resistance training and curcumin on the brain and motor performance of rats with cerebral ischemia using a model of bilateral common carotid artery occlusion. Functional tests were performed to analyze rats' motor performance, namely parallel bar test and misstep test. For nerve tissue analysis, Nissl staining and neuronal counting were performed in the cerebral cortex, striatum and hippocampus of the brains. Two protocols of high-intensity physical training were performed for six weeks, five days a week, from 20 to 40 min. The results demonstrated that there were significant differences in the parallel bar test and misstep test regarding the number of errors committed by the trained animals in comparison to the sedentary ones and the group that received curcumin. With respect to the number of neurons in the cortex and striatum, a lower neuronal density was observed in the trained animals. Thus, the animals of the sedentary group and the group that received curcumin exhibited better motor performance and higher neuronal density in the areas assessed, demonstrating that high-intensity physical exercise increased brain injury and worsened animals' motor performance.

BACKGROUND:Candida albicans is the main agent that causes vulvovaginal candidiasis. Resistance among isolates to azole antifungal agents has been reported. AIMS:Due to the well-known antifungal potential of curcumin, the purpose of this work was to evaluate the in vitro anticandidal activity of curcumin and its effect in the treatment of experimental vulvovaginal candidiasis. METHODS:The anticandidal activity of curcumin was investigated against eight Candida strains by the broth microdilution assay, and its mechanism of action was evaluated by testing the binding to ergosterol. Then, the effect of curcumin in the treatment of vulvovaginal candidiasis was evaluated in an immunosuppressed, estrogen treated rat model. RESULTS:Curcumin showed minimum inhibitory concentration values of 125-1000μg/ml, and the best result was observed against Candida glabrata. The compound was shown to be able to bind to the ergosterol present in the membrane, event that may be the mechanism of action. In addition, in the in vivo model of vulvovaginal candidiasis with C. albicans, treatments reduced the vaginal fungal burden in infected rats after seven days of treatment with different doses. CONCLUSIONS:Curcumin could be considered a promising effective antifungal agent in the treatment of vulvovaginal candidiasis.