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Gliomas are among the most common primary malignant brain tumors. Despite advances in cancer treatment, survival is very low, so the discovery of new therapeutic agents is essential. In this context, indole is an important source for the development of new bioactive molecules. A pharmacological screening of ten indole derivatives was carried out to evaluate the cytotoxic capacity against three tumor cell lines. After pharmacological screening, three compounds were selected, based on their high capacity to reduce cell proliferation, and their IC50 values were determined. Compound 9 exhibited the highest cytotoxic activity (IC50 = 0.4 µg/mL) in gliomas (C6 cell line), and were selected for further experiments. C6 cells were treated with compound 9 to evaluate cellular mechanisms such as colony formation and cell migration capacity and morphological alterations. Compound 9 decreased clone formation (0.4 and 0.8 µg/mL), and inhibited migration (0.2-0.8 µg/mL) in C6 cells. Morphological changes in cells treated with the compound 9 were also observed, such as chromatin condensation, and disorganization in cellular stress beams. Indole derivatives had a cytotoxic effect on tumor cells, and compound 9 showed the best anti-proliferative and anti-migratory activity in glioma cells.

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BACKGROUND: Lung cancer is the deadliest type of cancer in the world and the search for compounds that can treat this disease is highly important. Lawsone (2-hydroxy-1,4-naphtoquinone) is a naphthoquinone found in plants from the Lawsone genus that show a high cytotoxic effect in cancer cell lines and its derivatives show an even higher cytotoxic effect. METHODS: Sulforhodamine B was used to evaluate the cytotoxic activity of compounds on tumor cells. Clonogenic assay was used to analyze the reduction of colonies and wound healing assay to the migratory capacity of A549 cells. Apoptosis and necrosis were analyzed by flow cytometer and Giemsa staining. Hemolysis assay to determine toxicity in human erythrocytes. RESULTS: Lawsone derivatives were evaluated and compound 1 (O-propargyllawsone) was the one with the highest cytotoxic effect, with IC50 below 2.5 µM in A549 cells. The compound was able to reduce colony formation and inhibit cell migration. Morphological changes and cytometry analysis show that the compound induces apoptosis and necrosis in A549 cells. CONCLUSIONS: These results show that O-propargyllawsone show a cytotoxic effect and may induce apoptosis in A549 cells.

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BACKGROUND: Plants of the Myrcia genus have been widely used in folk medicine to treat various diseases, including cancer. Myrcia splendens species has a diverse chemical constitution, but the biological activities of its essential oil have not been well investigated. In this study to out the chemistry characterization of essential oil (EO) from the leaves of the species M. splendens from Brazil and evaluate cytotoxic effect in A549 lung cancer cells. METHODS: M. splendens EO was obtained by hydrodistillation and analyzed by Gas Chromatography-Mass Spectrometry (GC-MS). EO was isolated and evaluated for cellular viability in tumor cell lines by MTT assay. The evaluation of the formation of clones and the migratory capacity of the A549 cells treated with EO was done by the clonogenic assay and the wound healing assay. Morphological changes were observed in A549 cells by fluorescence using Phalloidin/FITC and DAPI. RESULTS: 22 compounds were identified in the chemical analysis of EO, corresponding to 88% of the sample. Major compounds were the sesquiterpenic hydrocarbons bicyclogermacrene (15.4%), germacrene D (8.9%) and E-caryophyllene (10.1%). The biological analysis of the EO showed high cytotoxic activity with an IC50 below 20 µg/ml in the THP-1, A549 and B16-F10 tumor cells. The treatment with EO reduced colony formation and inhibited the migratory capacity of A549 cells. Furthermore, apoptotic morphological changes in the nucleus and cytoplasm of A549 cells was observed after of treatment with EO. CONCLUSION: The findings of this study suggest that the M. splendens EO has cytotoxic compounds for the A549 lung cancer cells. Treatment with the EO decreased the colony formation and reduced the ability of lung cancer cells to migrate. Future studies may be used to isolate compounds from the EO for the study of lung cancer.

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Dental plaque (DP) is found on the surface of teeth and comprises a community of microorganisms that form a structured biofilm. Bacteria present in DP are potential periodontal pathogens when there is an imbalance in the healthy oral environment, and are precursors of periodontal disease (PD). In dogs, the treatments, such as mechanical removal, are difficult and expensive to apply. Therefore, in order to seek new therapeutic alternatives to control dental plaque in dogs, Brazilian red propolis ethanol extract (RPEE) was tested to evaluate its antibacterial effect on bacteria isolated from DP of dogs without PD. DP was collected from the supragingival dental surfaces of 10 dogs. Bacterial isolates of DP were identified by PCR and sequencing of 16S rDNA gene. The RPEE was obtained using the ultrasound ethanol extraction technique, and the chemical composition was obtained by HPLC-DAD and UV-spectrophotometry. In total, 29 different bacteria belonging to five genera were identified. Formononetin, biochanin A, liquiritigenin and daidzein were the major constituents of the RPEE. The cytotoxic effect showed cell viability after 24 h above 50 % at all concentrations evaluated. The minimum inhibitory concentration was between 37.5 and 150.0 µg/mL for all bacterial isolates. The minimal bactericidal concentration was between 150 and 1200 µg/mL for Gram-positive and 300-1200 µg/mL for Gram-negative bacteria. The results are promising and suggest that RPEE has significant antibacterial potential against the bacteria present in the DP of healthy dogs. Although further studies are still needed, the results suggest RPEE might be safely used in the prevention of periodontal disease.

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Schistosomiasis is a neglected tropical disease that affects millions of people around the world. Currently, the only drug available for the treatment of this disease is praziquantel, which has low efficacy against immature helminth stages and there are reports of drug resistance. In this study, the chemical composition and the in vitro effect of essential oils (EOs) and major compounds from Lippia gracilis and Lippia alba against schistosomula and adult Schistosoma mansoni worms were evaluated. Adult S. mansoni worms cultured for 8h in the presence of L. gracilis EO (50 and 100 µg/mL) or for 2h with its major compound, carvacrol (100 µg/mL), had a 100% reduction in viability. After interaction with L. alba EO (100µg/mL), there was a reduction of approximately 60% in the viability of adult worms after 24 hours of exposure; citral (50 and 100 µg/mL), its major compound, reduced the viability after 24 hours by more than 75%. Treatment of schistosomula with 100 µg/mL of L. gracilis or L. alba EOs for 6h led to a reduction in parasite viability of 80% and 16% respectively. Both EOs and their major compounds significantly reduced the oviposition of adult worms exposed to a non-lethal concentration (5 µg/mL). In addition, morphological changes such as the destruction of the tegument and disorganization of the reproductive system of male and female worms were visualized. Both EOs showed low cytotoxicity at a concentration of 50 µg/mL. The results encourage further investigation of these plants as a potential source of bioactive compounds against S. mansoni.

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There is not a described method to count the core label of c-Fos-positive neurons, avoiding false-positive and false-negative results. The aim of this manuscript is to provide guidelines for a secure and accurate method to calculate a threshold to select which core of c-Fos-positive neurons marked by immunofluorescence has to be scored. A background percentage was calculated by dividing the intensity value (0 to 255) of the core of c-Fos-positive neurons by its surrounding background from the 8-bit images obtained in a previous study. Using the background percentage from 20% up to 98%, raising 2% once for each score, as threshold to choose which core has to be counted, a script was written for the R program to count the number of the c-Fos-positive neurons and the comparison between control and experimental groups. The differences of the average number of the core counted c-Fos-positive neurons between control and experimental groups, at all thresholds studied, showed a rising value related to an increase of the background percentage threshold as well as a decrease of its p value related to an increase of the threshold of background percentage. For the smallest thresholds (high intensity of label), the differences between groups are suppressed (false negative). However, for the biggest thresholds (nonspecific label), these differences are always the same (false positive). Therefore, to avoid the false-negative and the false-positive values, it was chosen as the threshold of 62% the inflection point of the linear regression, which is equally different from the biggest and smallest values of the differences between groups.

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Neurodegenerative diseases affect millions of people worldwide. Regardless of the underlying cause, neuroinflammation is the greatest risk factor for developing any of these disorders. Pectolinarigenin (PNG) is an active flavonoid with several biological properties, anti-metastatic and anti-inflammatory activity. This study investigate the biological effects of PNG in macrophage and astrocyte cultures, with focus on elucidating the molecular mechanisms involved in the PNG activity. J774A.1 murine macrophage or cerebral cortex primary astrocytes primary cultures were treated with different concentration of PNG (1-160 µM) and the inflammatory process was stimulated by LPS (1 µg/ml) and the effect of PNG in different inflammatory markers were determined. PNG did not affect astrocyte or macrophage viability. Moreover, this flavonoid reduced NO• release in macrophages, attenuated astrocyte activation by preventing the overexpression of glial fibrillary acidic protein, and decreased the release of inflammatory mediators, IL-1ß and IL-6 induced by LPS by the glial cell, as well as enhanced basal levels of IL-10. In addition, PNG suppressed NFκB, p38MAPK and ERK1/2 phosphorylation in astrocytes culture induced by LPS. The results show clear evidence that this novel flavonoid protects astrocytes against LPS-induced inflammatory toxicity. In conclusion, PNG presents neuroprotective and anti-inflammatory property through the inhibition of inflammatory signaling pathways.

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BACKGROUND: Melanoma is a malignant cancer that affects melanocytes and is considered the most aggressive skin-type cancer. The prevalence for melanoma cancer for the last five year is about one million cases. The impact caused of this and other types of cancer, revel the importance of research into potential active compounds. The natural products are an important source of compounds with biological activity and research with natural products may enable the discovery of compounds with potential activity in tumor cells. METHODS: The Sulforhodamine B was used to determine cell density after treatment with lawsone derivatives. Apoptosis and necrosis were analyzed by flow cytometer. Morphological changes were observed by fluorescence using the Phalloidin/FITC and DAPI stains. The clonogenic and wound healing assays were used to analyze reduction of colonies formation and migratory capacity of melanoma cells, respectability. RESULTS: In pharmacological screening, seven compounds derived from lawsone were considered to have high cytotoxic activity (GI > 75%). Three compounds were selected to assess the inhibitory concentration for 50% of cells (IC50), and the compound 9, that has IC50 5.3 µM in melanoma cells, was selected for further analyses in this cell line. The clonogenic assay showed that the compound is capable of reducing the formation of melanoma colonies at 10.6 µM concentration. The compound induced apoptotic morphological changes in melanoma cells and increased by 50% the cells dying from apoptosis. Also, this compound reduced the migratory capacity of melanoma cells. CONCLUSIONS: The results of this study showed that the evaluated lawsone derivatives have potential activity on tumor cells. The compound 9 is capable of inducing cell death by apoptosis in melanoma cells (B16F10).

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The aim of this present study was to evaluate the effect of solid lipid nanoparticles (SLN) containing carvacrol over the lung damage of airway smoke inhalation. The study was conducted with 30 rats subjected to smoke inhalation and divided into 5 groups such as, normal control, negative control, oxygen group, SLN alone, and SLN+CARV group. The animals were sacrificed 24 h after the induction of inhalation injury further, the tissues of larynx, trachea, and lungs were collected for the histological, hematological, myeloperoxidase, and malondialdehyde analysis. The obtained results showed that treatment with CARV+SLN minimized the inhalation injury, since it reduced malondialdehyde significantly, when compared to the negative control group and minimized the histological changes which proves the absence of pulmonary emphysema and exudate in laryngeal and tracheal lumen in the CARV+SLN-treated group. Meanwhile, the presence of lesion with chronic characteristics was observed in the negative control and oxygen groups. It is suggested that the SLN containing carvacrol minimized oxidative stress and histological damages generated from smoke inhalation in rodents.

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BACKGROUND: Oncological pain is one of the most prevalent and difficult-to-treat symptoms in patients with cancer. p-Cymene (PC) is a monoterpene found in more than 100 different plant species, endowed with various pharmacological properties-particularly antinociceptive. HYPOTHESIS/PURPOSE: PC has antinociceptive effect in a model of oncologic pain due to the activation of the descending inhibitory pathway of pain. STUDY DESIGN: A pre-clinical, longitudinal, blind and randomized study. METHODS: Male Swiss mice were induced with S180 cells in the right hind paw, then treated daily with PC (12.5, 25 and 50 mg/kg, s.c.) and screened for mechanical hyperalgesia, spontaneous nociception, nociception induced by non-noxious palpation, tumor growth, changes in the neuromuscular function and existence of bone degradation in the tumor area. The effect of PC on Ca2+ currents (electrophysiological records), histological and neurochemical changes (immunofluorescence for Fos) were also evaluated. RESULTS: PC reduced (p < 0.05) the mechanical hyperalgesia, the spontaneous (p < 0.001) and non-noxious palpation (p < 0.001) nociceptions, not changing the tumor development, neuromuscular function or histopathological aspects of the paw affected. PC reduced Fos expression in the spinal cord (p < 0.001) and increased this expression in the PAG (p < 0.05) and in the NRM (p < 0.01). PC decreased the density of calcium channel currents (p < 0.05). CONCLUSION: These results suggest the antinociceptive effect of PC on oncologic pain, probably acting in both ascending and descending pain pathways, and modulating the calcium channel currents in order to exert its effects.

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We evaluated if a nanostructured thermoreversible Pluronic F127-based hydrogel incorporated with Hyptis pectinata leaf essential oil (NE-EOH) produces a long-lasting anti-hyperalgesic effect on chronic muscle pain in an animal model. We induced chronic muscle pain by injecting the gastrocnemius with saline injections. Paw and muscle withdrawal thresholds and motor performance were evaluated after treatment and compared with morphine, diazepam, or vehicle. Naloxone and methysergide administration tested the involvement of opioid and serotonin receptors, respectively. Sites of action in the central nervous system for the NE-EOH were examined by measuring substance P (SP) levels in the spinal cord and Fos protein in the brainstem. NE-EOH increased paw and muscle withdrawal thresholds when compared with vehicle but had no effect on motor function. This analgesic effect was reversed by both naloxone and methysergide. NE-EOH decreased elevated substance P levels and reduced Fos-labeled neurons in the spinal cord and increased the number of Fos-labeled neurons in the periaqueductal gray (PAG), nucleus raphe magnus (NRM), and locus coeruleus (LC). NE-EOH was shown to produce a lasting anti-hyperalgesic effect. It uses opioid and serotonin receptors, activates brainstem inhibitory pathways, and reduces the release of excitatory neurotransmitters in the spinal cord and is a substance with potential to be used in the treatment of noninflammatory pain conditions. Graphical Abstract.

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BACKGROUND: The inhalation injury is usually initiated by uninhibited absorption of smoke, favoring the release of cytokines and other lipid mediators from inflammatory cells in lung airways and parenchyma. OBJECTIVES: To systematically review, examine, and synthesize the main inflammatory mediators analyzed in published studies in animals subjected to smoke inhalation, as well as oxidative stress. SEARCH STRATEGY: A comprehensive literature search was conducted through MEDLINE-PubMed, Web of Science, and Scopus. SELECTION CRITERIA: Studies with animals subjected to lung damage from smoke inhalation that evaluated the presence and the action of inflammatory mediators and oxidative stress. RESULTS: A total of 1332 studies were initially identified, with only 31 meeting the inclusion criteria. The inflammatory mediators and oxidative stress markers studied and presented in the articles described herein were varied; however, the most cited ones were tumor necrosis factor-alpha (6), IL-8 and IL-6 (both studied in five articles), IL-1ß and nuclear factor kappa ß (both studied in 4 articles), malondialdehyde (11 studies), and myeloperoxidase (7). It is worth noting that most studies evaluated more than one inflammatory mediator and oxidative stress marker. CONCLUSION: Based on this review, we could observe that the main inflammatory mediators and oxidative stress markers analyzed were TNF-α, IL-8, IL-6, IL-1ß, nuclear factor kappa ß, MDA, and MPO. However, it is necessary to increase the rigor of study design and data, in order to have studies that are more homogeneous and with appropriate methodological quality.

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The aim of this study was to investigate the wound-healing activity of (-)-borneol (BOR) incorporated in chitosan film on healing protocol in rodents. To assess the BOR wound-healing potential, male Wistar rats were subjected to a full-thickness excisional wound. The animals were divided into three groups: dressed with chitosan-based film (QUIN); dressed with chitosan-based film containing 0·5% BOR (QUIBO05); or dressed with chitosan-based film containing 1% BOR (QUIBO1). Dressing the wound areas and histological analysis were performed on the 3rd, 7th, 14th, and 21st days. The myeloperoxidase (MPO) activity was assessed on the third and seventh days after surgical procedures. Wounds dressed with chitosan-based film containing BOR reduced significantly the MPO activity (P < 0·001), showed significantly larger wound retraction rates (7 days, P < 0·05), improved the granulation reaction, and also provided better collagenisation density and arrangement during wound healing. It is suggested that BOR modulates the wound-healing process and is a promising compound to be used in wound care. This product may be quite useful in improving wound healing and could be a new biotechnological product with healing properties and clinical application. Further ongoing studies will enable us to understand the precise mechanisms whereby BOR improves the wound-healing process.

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The present study aimed to investigate the antinociceptive and anti-inflammatory effects of the cyclic dipeptide cyclo-Gly-Pro (CGP) in mice. Antinociceptive activity was assessed by employing different pain models, such as formalin test, acetic acid-induced writhing, hot plate test, and carrageenan-induced hyperalgesia, in mice. The number of c-Fos-immunoreactive cells in the periaqueductal gray (PAG) was evaluated in CGP-treated mice. Anti-inflammatory activity was evaluated using paw oedema induced by carrageenan, compound 48/80, serotonin, and prostaglandin E2 (PGE2) and analyzed by plethysmometry. Quantitation of myeloperoxidase (MPO) in the paw was carried out to analyze the presence of neutrophils in the tissue. Intraperitoneal injection of CGP produced a significant inhibition in both neurogenic and inflammatory phases of formalin-induced pain. The antinociceptive effect of CGP, evaluated in the acetic acid-induced writhing test, was detected for up to 6 h after treatment. Further, in the hot plate test, antinociceptive behaviour was evoked by CGP, and this response was inhibited by naloxone. Animals treated with CGP did not present changes in motor performance. In CGP-treated mice there was an increase in the number of c-Fos-positive neurons in the periaqueductal gray. In another set of experiments, CGP attenuated the hyperalgesic response induced by carrageenan. Furthermore, CGP also reduced the carrageenan-increased MPO activity in paws. In addition, CGP also reduced the paw oedema evoked by compound 48/80, serotonin, and PGE2 . Taken together, these results may support a possible therapeutic application of the cyclic dipeptide cyclo-Gly-Pro toward alleviating nociception and damage caused by inflammation conditions.

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This study aimed to evaluate the orofacial antinociceptive effect of the Cymbopogon winterianus essential oil (LEO) complexed in ß-cyclodextrin (LEO-CD) and to assess the possible involvement of the central nervous system (CNS). The LEO was extracted, chromatographed, and complexed in ß-cyclodextrin. The complex was characterized by differential scanning calorimetry (DSC) and thermogravimetry derivative (TG/DTG). Male Swiss mice (2-3 months) were treated with LEO-CD (50-200 mg/kg, p.o.), vehicle (distilled water, p.o.), or standard drug (i.p.) and subjected to the orofacial nociception formalin-, capsaicin-, and glutamate-induced. After the formalin test, the animals were perfused and the brains subjected to immunofluorescence for Fos. The rota-rod test (7 rpm/min) was carried out. Geraniol (37.57%) was the main compound of LEO. DSC and TG/DTG proved the complexation. The orofacial nociceptive behavior was significantly (p < 0.05) reduced. The number of Fos-positive cells was significantly changed in the dorsal raphe nucleus (p < 0.01), locus coeruleus (p < 0.001), trigeminal nucleus (p < 0.05), and trigeminal thalamic tract (p < 0.05). LEO-CD did not cause changes in motor coordination in the rota-rod test. Thus, our results suggested that LEO-CD has an orofacial antinociceptive profile, probably mediated by the activation of the CNS without changing the motor coordination.

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We evaluated the anti-hyperalgesic effect of citronellol (CT) and investigated the spinal cord lamina I involvement in this effect. Male mice were pre-treated with CT (25, 50 and 100mg/kg, i.p.), indomethacin (10mg/kg, i.p.), dipyrone (60mg/kg, i.p.) or vehicle (saline+Tween 80 0.2%). Thirty minutes after the treatment, 20µL of carrageenan (CG; 300µg/paw), PGE2 (100ng/paw), dopamine (DA; 30µg/paw) or TNF-α (100pg/paw) were injected into the hind paw subplantar region and the mechanical threshold was evaluated with an electronic anesthesiometer. The CT effect on edema formation was evaluated after the right paw subplantar injection of CG (40µL; 1%) through the plethysmometer apparatus. To evaluate the CT action on the spinal cord, the animals were treated with CT (100mg/kg; i.p.) or vehicle (Saline+Tween 80 0.2%; i.p.) and, after 30min, 20µL of CG (300µg/paw; i.pl.) was injected. Ninety minutes after the treatment, the animals were perfused, the lumbar spinal cord collected, crioprotected, cut and submitted in an immunofluorescence protocol for Fos protein. CT administration produced a significantly reduction (p<0.05) in the mechanical hyperalgesia induced by CG, TNF-α, PGE2 and DA when compared with control group. The treatment with CT also significantly (p<0.05) decreased the paw edema. The immunofluorescence showed that the CT decrease significantly (p<0.05) the spinal cord lamina I activation. Thus, our results provide that CT attenuates the hyperalgesia, at least in part, through the spinal cord lamina I inhibition.

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CONTEXT: Pain corresponds to the most frequent reason for visits to physicians, and its control by conventional drugs is accompanied by several side effects, making treatment difficult. For this reason, new chemical entities derived from natural products still hold great promise for the future of drug discovery to pain treatment. OBJECTIVE: The objective of this study was to evaluate the antinociceptive and anti-inflammatory profiles of p-cymene (PC), a monocyclic monoterpene, and its possible mechanisms of action. MATERIALS AND METHODS: Mice treated acutely with PC (25, 50, or 100 mg/kg, i.p.) were screened for carrageenan-induced hyperalgesia and the inflammatory components of its cascade (30-180 min), carrageenan-induced pleurisy (4 h), and tail-flick test (1-8 h). Also, we observed the PC effect on the generation of nitric oxide by macrophages and the activation of neurons in the periaqueductal gray (PAG) by immunofluorescence. RESULTS: PC reduced (p < 0.001) the hyperalgesia induced by carrageenan, TNF-α, dopamine, and PGE2. PC decrease total leukocyte migration (100 mg/kg: p < 0.01), neutrophils (50 and 100 mg/kg: p < 0.05 and 0.001), and TNF-α (25, 50, and 100 mg/kg: p < 0.01, 0.05, and 0.001, respectively), besides reducing NO production (p < 0.05) in vitro. PC produced antinociceptive effect in tail-flick test (p < 0.05), which was antagonized by naloxone, naltrindole, nor-BNI, and CTOP, and increased (p < 0.001) the number of c-Fos-immunoreactive neurons in PAG. DISCUSSION AND CONCLUSION: These results provide information about the anti-hyperalgesic and anti-inflammatory properties of PC suggesting a possible involvement of the opioid system and modulating some pro-inflammatory cytokines.

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AIMS: The present study evaluated the carvacrol (CARV) effect on hyperalgesia and nociception induced by sarcoma 180 (S180) in mice. MAIN METHODS: Carvacrol treatment (12.5-50mg/kgs.c.) once daily for 15days was started 24h after injection of the sarcoma cells in the hind paw (s.c.). Mice were evaluated for mechanical sensitivity (von Frey), spontaneous and palpation-induced nociception, limb use and tumor growth on alternate days. CARV effects on the central nervous system were evaluated through immunofluorescence for Fos protein. Molecular docking studies also were performed to evaluate intermolecular interactions of the carvacrol and muscimol, as ligands of interleukin-10 and GABAA receptors. KEY FINDINGS: CARV was able to significantly reduce mechanical hyperalgesia and spontaneous and palpation-induced nociception, improve use paw, decrease the number of positively marked neurons in lumbar spinal cord and activate periaqueductal gray, nucleus raphe magnus and locus coeruleus. CARV also caused significant decreased tumor growth. Docking studies showed favorable interaction overlay of the CARV with IL-10 and GABAA. SIGNIFICANCE: Together, these results demonstrated that CARV may be an interesting option for the development of new analgesic drugs for the management of cancer pain.

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Snakebites are a public health problem, especially in tropical countries. However, treatment with antivenom has limited effectiveness against venoms' local effects. Here, we investigated the ability of Abarema cochliacarpos hydroethanolic extract (EAc) to protect mice against injection of Bothrops leucurus venom. Swiss mice received perimuscular venom injection and were subsequently treated orally with EAc in different doses. Treatment with EAc 100, 200, and 400 mg/kg reduced the edema induced by B. leucurus in 1%, 13%, and 39%, respectively. Although lower doses showed no antihypernociceptive effect in the Von Frey test, the higher dose significantly reduced hyperalgesia induced by the venom. Antimyotoxic activity of EAc was also observed by microscopy assessment, with treated muscles presenting preserved structures, decreased edema, and inflammatory infiltrate as compared to untreated ones. Finally, on the rotarod test, the treated mice showed better motor function, once muscle fibers were preserved and there were less edema and pain. Treated mice could stand four times more time on the rotating rod than untreated ones. Our results have shown that EAc presented relevant activities against injection of B. leucurus venom in mice, suggesting that it can be considered as an adjuvant in the treatment of envenomation.

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