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Objectives: Araçá-verdadeiro is the popular name of Psidium guineense (Myrtaceae), whose fruits and leaves are used in Brazilian folk medicine for treatment of inflammation and pain. The focus of the present research was an investigation of the anti-nociceptive, and anti-inflammatory effects of the essential oil from P. guineense (EOPG) leaves, and of spathulenol. The anxiolytic and antidepressive effects associated with chronic pain were also investigated in models of acute or persistent nociception or/and inflammatory pain. Methods and Results: Oral treatment with EOPG (10-100 mg/kg) or spathulenol (10 mg/kg) significantly inhibited formalin-induced nociceptive responses, both sensitivity to cold and edema. Oral treatment with EOPG (10 mg/kg) and spathulenol (10 mg/kg) did not reduce locomotor activity (open field test). Local administration of spathulenol (1000 µg/paw) significantly prevented formalin-induced nociceptive sensitivity to cold and paw edema, and carrageenan-induced mechanical hyperalgesia, paw edema and sensitivity to cold. In the Freund's complete adjuvant (CFA) model, oral treatment with EOPG (10 mg/kg) or spathulenol (10 mg/kg) for 21 days significantly inhibited all analyzed parameters. The percentage maximal inhibition by spathulenol was 76.00% (mechanical hyperalgesia), 71.90% (cold response), 85.00% (edema), 77.16% (myeloperoxidase activity), 97.72% (time in the closed arms in the elevated plus maze), and 49.00% (immobility time in the tail suspension test), in the CFA model. Models employed male Swiss mice, except for the CFA test, which employed C57bL6 male mice ( n =6 /group). Conclusion: This study demonstrates that EOPG is an anti-nociceptive and anti-hyperalgesic agent, in acute and continuous treatment, and an anxiolytic and antidepressive agent when tested with the chronic pain experimental state.

Ethnopharmacological Relevance: Leaves from Psidium guineense Sw. are used in popular medicine for the treatment of inflammatory disease. However, there is no scientific evidence demonstrating this activity., Aim of the Study: To evaluate the antioxidant, anti-inflammatory, antiproliferative and antimycobacterial activities of the essential oil of P. guineense and spathulenol (a major constituent). The study was conducted in part to provide evidence supporting the ethnobotanical use of the leaves of this species., Material and Methods: The essential oil (EOPG) was extracted from the leaves of P. guineense by hydrodistillation and analysed by gas chromatography-mass spectrometry (GC-MS). The major compound, spathulenol (PG-1), was isolated in a chromatographic column and characterized by nuclear magnetic resonance (NMR). EOPG and PG-1 were evaluated in vitro for antioxidant activity by DPPH, ABTS and MDA methods; anti-inflammatory potential was assessed using two models, including pleurisy and oedema, in mice. The impact of EOPG and PG-1 on cell proliferation was determined via spectrophotometric quantification of the cellular protein content using a sulforhodamine B assay, and anti-Mycobacterium tuberculosis activity was determined using the REMA method., Results: A total of 38 components were identified from the EOPG, with the sesquiterpenic alcohol spathulenol (PG-1) (80.7%) being the major constituent. EOPG and PG-1 exhibited the highest antioxidant activities in the DPPH and MDA system compared with reference standard, with IC 50 values ranging from 26.13 to 85.60μg/mL. Oral administration of EOPG and PG-1 showed significant inhibition in the Cg-induced mice paw oedema and pleurisy model. The EOPG (GI 50 = 0.89μg/mL) and PG-1 (GI 50 = 49.30μg/mL) were particularly effective against the ovarian cancer cell line. Both showed moderate antimycobacterial activity., Conclusion: For the first time, this study demonstrated the antioxidant, anti-inflammatory, antiproliferative and antimycobacterial properties of the essential oil of P. guineense (leaves were collected in Dourados-MS) and spathulenol, collaborating the etnhopharmacologycal use of this plant due to its an anti-inflammatory effect., (Copyright © 2017. Published by Elsevier B.V.)

Leishmaniasis is a term referring to a range of clinical conditions caused by protozoan parasites of the genus Leishmania, Trypanosomatidae family, Kinetoplastida order that is transmitted by the bite of certain species of mosquitoes Phlebotominae subfamily. These parasites infect hosts wild and domestic mammals, considered as natural reservoirs and can also infect humans. Leishmania are obligate intramacrophage protozoa that have exclusively intracellular life style. This suggests that the amastigotes possess mechanisms to avoid killing by host cells. Cutaneous leishmaniasis, the most common form of the disease, causes ulcers on exposed parts of the body, leading to disfigurement, permanent scars, and stigma and in some cases disability. Many studies concluded that the cytokines profile and immune system of host have fundamental role in humans and animals natural self-healing. Conventional treatments are far from ideals and the search for new therapeutic alternatives is considered a strategic priority line of research by the World Health Organization. A promising approach in the field of basic research in homeopathy is the treatment of experimental infections with homeopathic drugs prepared from natural substances associations highly diluted, which comprise a combination of several different compounds considered as useful for a symptom or disease. Therefore, this study aimed to evaluate the effect of M1, a complex homeopathic product, in macrophage-Leishmania interaction in vitro and in vivo. It was used RAW cells lineage and BALB/c mice as a host for the promastigotes of L. amazonensis (WHOM/BR/75/Josefa). Several biochemical and morphological parameters were determined. Together, the harmonic results obtained in this study indicate that, in general, the highly diluted products trigger rapid and effective responses by living organisms, cells and mice, against Leishmania, by altering cytokines profile, by NO increasing (p<0.05), by decreasing parasitic load (p<0.001), and modifying classical maturation and biogenesis of parasitophorous vacuoles (p<0.001). M1 complex decreased endocytic index (p<0.001), and the % of infected macrophages (p<0.05), preventing the development of lesions (p<0.05) caused by L. amazonensis by increasing Th1 response (p<0.05). Therefore the M1complex can be a good candidate for a complementary therapy to conventional treatments, since all the parameters observed in vitro and in vivo improved. It could be an interesting clinical tool in association to a classical anti-parasitic treatment, maybe resulting in better quality of life to the patients, with less toxicity., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Forty Nellore heifers were fed (73days) with different diets: with or without essential oils (clove and/or rosemary essential oil) and/or active principle blend (eugenol, thymol and vanillin). The pH, fat thickness, marbling, muscle area and water losses (thawing and drip) were evaluated 24h post mortem on the Longissimus thoracis, and the effects of aging (14days) was evaluated on the meat cooking losses, color, texture and lipid oxidation. Antioxidant activity was also evaluated. Treatments had no effect (P>0.05) on pH, fat thickness, marbling, muscle area, thawing and drip losses. However, treatments affected (P<0.05) cooking losses, color, texture and lipid oxidation. The diets with essential oil and the active principle blend reduced the lipid oxidation and reduced the color losses in relation to control diet. Aging affected (P<0.05) texture and lipid oxidation. The essential oil and active principles or its blend have potential use in animal feed aiming to maintain/improve meat quality during shelf-life., (Copyright © 2017. Published by Elsevier Ltd.)

Background: In previous results mice treated with high dilutions of antimony presented reduction of monocyte migration to the site of infection with increase in B lymphocytes population in the local lymph node., Aims: To know the mechanisms involved, a series of in vitro studies was done, using co-cultures of macrophages (RAW 264.7) and Leishmania (L.) amazonensis treated with different dilutions of antimony (Antimonium crudum or AC), in different times., Methodology: Spreading, phagocytosis, the oxidative activity of macrophages, the viability of free promastigotes and the cytokines/chemokines concentration in the supernatant were evaluated. The assays were performed in quadruplicate., Results: Cells treated with AC 30cH (10 -58 M) and AC 200cH (10 -398 M) presented a temporary reduction of the spreading after 02h of incubation, followed by increase after 48h, being the most significant increase observed after the AC 200cH treatment. However, the percentage of internalized parasites at 48, 96 and 120h of incubation was also higher in cells treated with AC 200cH. It is suggested that the AC 200cH improves the ability of phagocytes to internalize the parasites, but not to digest them. The cytokines-chemokines panel corroborated these results. Both dilutions potentiated the parasite-induced reduction of cytokines production, especially IL-6, IL 12 p40 and γ-IFN, after 48h of incubation. In addition, the production of MIP-1 beta (CCL4), a chemokine involved in chronic inflammation, was also reduced after 120h. A specific effect of AC 30cH was seen by the inhibition of two peaks of CCL2 (MCP-1) observed in infected macrophages, at 24 and 120h. Since this cytokine is an important chemokine for monocytes, it explains the results obtained formerly in vivo. The morphology of macrophages after acridine orange staining revealed that the treatment with AC 30cH reduced substantially the acid vacuoles in the cytoplasm, indicating a certain inability of these cells to digest the parasites. On the other hand, a large peak of VEGF-A, associated with increase of internalized parasites was observed after 120h of treatment with AC 200cH, which could be associated to the regulation of the chronic inflammation events by M1-M2 polarization. There was no statistical difference among groups regarding the production of TNF, NO and H 2 O 2 , showing that the drugs do not alter macrophage cytotoxic activity. A clear quantitative and qualitative variation of the modulatory effects of AC 30cH and 200cH was seen, in function of time., Conclusions: Both dilutions were able to potentiate the decrease of most of cytokines and chemokines induced by the parasite infection in vitro, which explains the clinical improvement seen previously in vivo, however, the mechanisms involved and the epidemiological significance of these findings are still under discussion., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

In this study, the contribution of liver glycogenolysis and gluconeogenesis in the defense against short-term insulin induced hypoglycemia (IIH) was investigated. For this purpose, we used an experimental model in which IIH was obtained by administering an IP injection of a pharmacological dose (1 U/kg) of regular insulin to rats that had been deprived of food for a period of six hours. This experimental model is suitable to study the simultaneous participation of glycogen breakdown and gluconeogenesis in the defense against IIH. The livers of IIH rats showed insignificant changes in the glycogen concentration, total phosphorylase, active phosphorylase, and percent of active phosphorylase. Our results also indicated that the livers of IIH rats that received the concentration of L-alanine, L-glutamine, L-lactate, or glycerol found in the blood during IIH (basal values) showed negligible glucose production. Nonetheless, glucose, urea, and pyruvate production increased (P<0.05) if the livers were perfused with a saturating concentration of gluconeogenic precursors. In agreement with these results, IIH rats that received intragastric L-alanine, L-glutamine, or L-lactate showed increased (P<0.05) glycemia 30 min after the administration of these substances. However, when using glycerol, higher glycemia (P<0.05) was observed at 2 and 5 min, but not 30 min after the administration of this hepatic gluconeogenic precursor. Thus, we can conclude that the oral availability of gluconeogenic precursors could allow for their use as important antidote in the defense against IIH.

The responsiveness of glycogen breakdown to cAMP was investigated in isolated perfused liver from male Wistar fed rats (200-220 g) with insulin-induced hypoglycemia. The activation of glycogenolysis by 3 microM cAMP was decreased (P<0.05) in livers from rats with hypoglycemia induced by the administration of insulin or during the direct infusion of insulin into the isolated liver. The direct effect of insulin on glycogen catabolism promoted by 3 microM cAMP occurred as early as 3 min after starting insulin infusion. In contrast, the cAMP agonists resistant to phosphodiesterases, 8Br-cAMP and 6MB-cAMP, used at the same concentration as cAMP, i.e., 3 microM, did not modify the effect of insulin. The data suggest that the decreased hepatic responsiveness of glycogen breakdown during insulin-induced hypoglycemia is a direct effect of insulin decreasing the intracellular levels of cAMP.