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Two lanthanide complexes supported on MCM48 type silica have been synthetized to introduce a new concept of multi-stimuli responsive materials for anti-counterfeiting applications. This new technology provides a simple and secure way of storing information with different levels of security from biocompatible materials. Different luminescent patterns can be revealed and suppressed by external stimuli: addition and removal of a specific reagent (chemical stimulus) followed by UV exposure to reveal the characteristic luminescence of the material and heat treatment (physical stimulus) to suppress the red luminescence of the material. The chemical stimulus occurs from the complexation of β-diketone 4,4,4-trifluoro-1-phenyl-1,3-butadione (BTFA) in the Eu(H2O)nL–SiO2 (L = chelidamic acid or trimesic acid) printed hybrid and can be made via insertion of the ligand by soaking the label using a marker pen. Physical stimuli can occur through a portable heat gun. The complexation with BTFA enhances the Eu-luminescence through the antenna effect under exposure to common UV-light. Heating (∼145 °C) for a few seconds rapidly quenches the luminescence of the label and, after some cycles of heating–cooling, BTFA sublimates and leads to complete quenching of the red luminescence. The combination of chemical and physical stimuli provides two levels of security verification and unbreakable encryption.

International audience; AIM: Hydroxycinnamic acids their derivatives have various pharmacological properties. The hydroxycinnamic acid derivatives, methyl cinnamate, trans-cinnamic, and p-coumaric acids have been the object of study in the treatment of skin wounds. However, it is unclear whether these derivatives exert a direct beneficial effect on fibroblast function. In this study, we evaluated the effects of methyl cinnamate, trans-cinnamic, and p-coumaric acids on fibroblast migration in vitro. MATERIALS AND METHODS: NIH 3T3 and L929 fibroblast cell lines were exposed to each drug at several concentrations and the effect on cell viability, cell cycle, and extracellular matrix production were assessed by MTT assay, flow cytometry, and immunofluorescence staining, respectively. The effect on cell migration was examined using scratch assay. RESULTS: The results showed that hydroxycinnamic acid derivatives not affect cell viability, but increase fibroblast migration in the in vitro scratch-wound healing assay. They also induced an increase in S and G2/M phases accompanied by a decrease in the G0/G1 phase of the cell cycle. The cell proliferation inhibitor mitomycin C abolished the effect induced by p-coumaric acid and methyl cinnamate, indicating that only the trans-cinnamic acid stimulated migration. A transwell migration assay confirmed that trans-cinnamic acid-treated fibroblasts exhibited increased migration compared with untreated cells. trans-Cinnamic acid-induced fibroblast migration was decreased by PKA inhibitor and p38-MAPK inhibitor but not by JNK inhibitor. Additionally, trans-cinnamic acid-treated fibroblasts showed an increase in the production of laminin and collagen type I. CONCLUSION: Our study showed that trans-cinnamic acid improves fibroblast migration and modulates extracellular matrix synthesis, indicating its potential for accelerating the healing process.

International audience; Uvaol is a natural pentacyclic triterpene that is widely found in olives and virgin olive oil, exerting various pharmacological properties. However, information remains limited about how it affects fibroblasts and endothelial cells in events associated with wound healing. Here, we report the effect of uvaol in the in vitro and in vivo healing process. We show the positive effects of uvaol on migration of fibroblasts and endothelial cells in the scratch assay. Protein synthesis of fibronectin and laminin (but not collagen type I) was improved in uvaol-treated fibroblasts. In comparison, tube formation by endothelial cells was enhanced after uvaol treatment. Mechanistically, the effects of uvaol on cell migration involved the PKA and p38-MAPK signaling pathway in endothelial cells but not in fibroblasts. Thus, the uvaol-induced migratory response was dependent on the PKA pathway. Finally, topical treatment with uvaol caused wounds to close faster than in the control treatment using experimental cutaneous wounds model in mice. In conclusion, uvaol positively affects the behavior of fibroblasts and endothelial cells, potentially promoting cutaneous healing.

Cyclo-Gly-Pro (CGP) attenuates nociception, however its effects on salivary glands remain unclear. In this study, we investigated the acute effects of CGP on salivary flow and composition, and on the submandibular gland composition, compared with morphine. Besides, we characterized the effects of naloxone (a non-selective opioid receptor antagonist) on CGP- and morphine-induced salivary and glandular alterations in mice. After that, in silico analyses were performed to predict the interaction between CGP and opioid receptors. Morphine and CGP significantly reduced salivary flow and total protein concentration of saliva and naloxone restored them to the physiological levels. Morphine and CGP also reduced several infrared vibrational modes (Amide I, 1687-1594cm-1; Amide II, 1594-1494cm-1; CH2/CH3, 1488-1433cm-1; C = O, 1432-1365cm-1; PO2 asymmetric, 1290-1185cm-1; PO2 symmetric, 1135-999cm-1) and naloxone reverted these alterations. The in silico docking analysis demonstrated the interaction of polar contacts between the CGP and opioid receptor Cys219 residue. Altogether, we showed that salivary hypofunction and glandular changes elicited by CGP may occur through opioid receptor suggesting that the blockage of opioid receptors in superior cervical and submandibular ganglions may be a possible strategy to restore salivary secretion while maintaining antinociceptive action due its effects on the central nervous system.

The supramolecular nano-aggregate CUR–CB[7] (CUR = curcumin and CB[7] = cucurbit[7]uril) was efficiently prepared by mixing CUR and CB[7] at a molar ratio of 1 : 1 in ethanol at room temperature. The supramolecular aggregate formation was evidenced by mainly FTIR, 1H NMR, DOSY and spectroscopy experiments. The supramolecular arrangement promotes the increase in the solubility and stability of CUR without affecting the biological properties of the A549 cells. The luminescence properties of CUR and CUR–CB[7] show anti-Kasha's rule fluorescence, and their remarkable NIR emission enables this material to be used as a luminescent probe and marker for in vivo tracking and structural integrity monitoring of the supramolecular complex.

Context: Propolis has promising biological activities. Propolis samples from the Northeast of Bahia, Brazil – sample A from Ribeira do Pombal and B, from Tucano – were investigated, with new information regarding their biological activities. Objective: This paper describes the chemical profile, antioxidant, anti-glycation and cytotoxic activities of these propolis samples. Material and methods: Ethanol extracts of these propolis samples (EEP) and their fractions were analyzed to determine total phenolic content (TPC); antioxidant capacity through DPPH•, FRAP and lipid peroxidation; anti-glycation activity, by an in vitro glucose (10 mg/mL) bovine serum albumine (1 mg/mL) assay, during 7 d; cytotoxic activity on cancer (SF295, HCT-116, OVCAR-8, MDA-MB435, MX-1, MCF7, HL60, JURKAT, MOLT-4, K562, PC3, DU145) and normal cell lines (V79) at 0.04–25 μg/mL concentrations, for 72 h. The determination of primary phenols by ultra high-pressure liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) and volatile organic compounds content by gas chromatography-mass spectrometry (GC-MS) were also performed. Results: The EEP polar fractions exhibited up to 90% protection against lipid peroxidation. The IC50 value for anti-glycation activity of EEP was between 16.5 and 19.2 μg/mL, close to aminoguanidine (IC50 = 7.7 μg/mL). The use of UHPLC-MS/MS and GC-MS allowed the identification of 12 bioactive phenols in the EEP and 24 volatile compounds, all already reported. Conclusions: The samples present good antioxidant/anti-glycation/cytotoxic activities and a plethora of biologically active compounds. These results suggest a potential role of propolis in targeting ageing and diseases associated with oxidative and carbonylic stress, aggregating value to them.

Selaginella convoluta (Arn.) Spring is a species popularly known as “jericó”, and used in folk medicine as analgesic and anti-inflammatory. This study aimed to investigate in mice the antinociceptive and anti-inflammatory activities of the hexane (Sc-Hex) and chloroform (Sc-CHCl3) fractions (100, 200 and 400 mg/kg) obtained by partition of crude ethanol extract from S. convoluta. The preliminary phytochemical analysis of the fractions was performed. Antinociceptive activity was evaluated by writhing, formalin and hot-plate tests. Anti-inflammatory activity was evaluated using carrageenan-induced pleurisy. The rota-rod test was used to evaluate motor coordination. Preliminary phytochemical screening showed that the Sc-Hex and the Sc-CHCl3 were positive for the presence of flavonoids, anthracene derivatives, quinones, triterpenes and steroids. Inhibition of writhing was observed for fractions tested. The Sc-Hex at all doses tested was effective in reducing the nociceptive behavior produced by formalin only in the second phase. However, the Sc-CHCl3 decreased the paw licking time in the first and second phases. In the hot plate no significant effect was observed for any fraction. In the rota-rod test, treated mice did not demonstrate any significant motor performance changes. In the carrageenan-induced pleurisy, Sc-CHCl3 (200 mg/kg) reduced cell migration to the pleural cavity. These results reveal the antinociceptive properties of S. convoluta , which support, in part, its traditional use, since the fractions did not presented significant activity in the inflammatory response profile. We further verify that this antinociceptive effect could be by activation of nociceptive peripheral pathway. Resumo Selaginella convoluta é uma espécie popularmente conhecida como “jericó”, e usada na medicina popular como analgésica e anti-inflamatória. Este estudo teve como objetivo investigar em camundongos as atividades antinociceptiva e anti-inflamatória das frações hexânica (Sc-Hex) e clorofórmica (Sc-CHCl3) (100, 200 e 400 mg/kg) obtidas por partição do extrato etanólico bruto de S. convoluta . A análise fitoquímica preliminar das frações foi realizada. A atividade antinociceptiva foi avaliada pelos testes de contorções abdominais, formalina e placa quente. A atividade anti-inflamatória foi avaliada usando pleurisia induzida por carragenina. O teste do rota-rod foi utilizado para avaliar a coordenação motora. A triagem fitoquímica preliminar mostrou que Sc-Hex e Sc-CHCl3 apresentaram reação positiva para a presença de flavonoides, derivados antracênicos, quinonas, triterpenos e esteroides. A inibição das contorções foi observada para as frações testadas. Sc-Hex em todas as doses testadas foi efetivo na redução do comportamento nociceptivo produzido pela formalina somente na segunda fase. No entanto, Sc-CHCl3 diminuiu o tempo de lambida da pata na primeira e segunda fases. Na placa quente, nenhum efeito significativo foi observado para qualquer fração. No teste do rota-rod os camundongos tratados não demonstraram mudanças significativas na coordenação motora. Na pleurisia induzida por carragenina, Sc-CHCl3 (200 mg/kg) reduziu a migração celular para a cavidade pleural. Estes resultados revelam a propriedade antinociceptiva de S. convoluta, justificando, em parte, seu uso tradicional, uma vez que os extratos não apresentaram atividade significativa no perfil de resposta inflamatória. Verificamos ainda que esse efeito antinociceptivo mostrou-se ligado à ativação da via periférica nociceptiva.

Underutilized parts of some abundant crops can be valuable and the search for additional uses, mainly in healthy and for social purposes are very attractive. This is the case of Cocos nucifera Linn., an important source of phenolic compounds and a native plant of tropical countries, widely distributed in the Northeast and North of Brazil. The objectives of this study were to determine the phenolic chemical composition, the photoprotection capacity, represented by sun protector factor (SPF), of the ethanol extract of coconut (Cocos nucifera) husk fiber of the yellow dwarf variety (EEYD) against UVB rays and after its incorporation into sunscreen formulations. Antiglycation activity [represented by bovine serum albumin (BSA) – glucose/fructose, Collagen – glucose/fructose and BSA-Methylglyoxal (MG) assays], using aminoguanidine (AG) as a positive control, and cytotoxic effects toward macrophages, were also evaluated. The identification of non-toxic antiglycation agents holds great promise in the development of alternative therapies for diseases, such as diabetes and their complications and is not often, reported in the literature. The determination of the SPF of the EEYD together with its sunscreen formulations was performed by in vitro method. A total of seven phenolic compounds, quercetin, catechin, epicatechin, vanillic, caffeic, 4-hydroxybenzoic and chlorogenic acids were identified by high performance liquid chromatography (HPLC)-UV/Vis and ultra high performance liquid chromatography - tandem mass spectrometer UHPLC-MS/MS. The present extract (EEYD) presented photoprotective activity with SPF values equivalent to the standards, benzophenone-3 and quercetin. The formulations prepared in different concentrations of the extract (5–20 % w/w) showed maximum SPF values of 15.94. The extract presented promising antiglycation activity, higher than the positive control, the pure compound aminoguanidine (AG), except for BSA/MG, with values for BSA/glucose/fructose of 9.61 μg/mL (vs.AG 18.30 μg/mL); for collagen/glucose/fructose of 4.50 μg/mL (vs.AG 82.87 μg/mL) and 34.76 μg/mL (vs.AG,13.19 μg/mL). The present ethanol extract does not decrease macrophage viability and presents a plethora of biologically active compounds. The combined results have shown the possibility of using non-toxic EEYD, as an active ingredient in sunscreen formulations and in the nutrition/medicinal areas, giving extra value to an environmental-unfriendly residue, with strong prospects for success.

International audience; Acute lung injury (ALI) remains to cause a high rate of mortality in critically ill patients. It is known that inflammation is a key factor in the pathogenesis of lipopolysaccharide (LPS)-induced ALI, which makes it a relevant approach to the treatment of ALI. In this study, we evaluated the potential of nasally instilled p-coumaric acid to prevent LPS-induced ALI in mice, by evaluating its effects on cellular and molecular targets involved in inflammatory response via in vitro and in silico approaches. Our results demonstrated that p-coumaric acid reduced both neutrophil accumulation and pro-inflammatory cytokine abundance, and simultaneously increased IL-10 production at the site of inflammation, potentially contributing to protection against LPS-induced ALI in mice. In the in vitro experiments, we observed inhibitory effects of p-coumaric acid against IL-6 and IL-8 production in stimulated A549 cells, as well as reactive oxygen species generation by neutrophils. In addition, p-coumaric acid treatment decreased neutrophil adhesion on the TNF-α-stimulated endothelial cells. According to the in silico predictions, p-coumaric acid reached stable interactions with both the ATP-binding site of IKKβ as well as the regions within LFA-1, critical for interaction with ICAM-1, thereby suppressing the production of proinflammatory mediators and hindering the neutrophil infiltration, respectively. Collectively, these findings indicate that p-coumaric acid is a promising anti-inflammatory agent that can be used for developing a pharmaceutical drug for the treatment of ALI and other inflammatory disorders.

This study evaluated the anti-allergenic properties of the aqueous extract of the stem bark from Bowdichia virgilioides (AEBv). Oral administration of AEBv inhibited the plasma protein leakage at 30 min post allergenic challenge in Swiss mice actively sensitized with ovalbumin (OVA). AEBv inhibited OVA-induced histamine release in vitro in tissues obtained from sensitized mice. AEBv-treated mice exhibited a lower influx of neutrophils and eosinophils in allergen-induced pleurisy 24 h post OVA-challenge. This treatment also reduced tumor necrosis factor (TNF)-α content in the pleural effluent. Furthermore, AEBv treatment drastically inhibited the high levels of interleukin (IL)-5 and CC chemokine eotaxin (CCL11) mRNA expression in pleural leukocytes after OVA-challenge. Preliminary toxic effects were assessed, and a qualitative phytochemical profile was performed. The extract contained condensate tannins, flavonoids, saponins, and steroids but not triterpenes and alkaloids. Oral treatment with AEBv did not induce signs of systemic toxicity or genotoxic effects. These results demonstrated that AEBv is a potent inhibitor of contributors to the allergic inflammatory response, supporting its use in folk medicine to treat allergic conditions. Key words: Bowdichia virgilioides, allergy, inflammation, natural product.

Naphthoquinone derivatives have various pharmacological properties. Here, we describe the synthesis of new 1,4-naphthoquinone derivatives inspired by lawsone and β-lapachone and their effects on both migration of fibroblasts in vitro and dermal wound healing in diabetic mice. NMR and FTIR spectroscopy aided characterization of chemical composition and demonstrated the molecular variations after the synthesis of four different derivatives, namely 2-bromo-1,4-naphthoquinone (termed derivative S3), 2-N-phenylamino-1,4-naphthoquinone (derivative S5), 2-N-isonicotinoyl-hydrazide-1,4-naphthoquinone (derivative S6), and 1-N-isonicotinoyl-hydrazone-[2-hydroxy-3-(3-methyl-2-butenyl)]-1,4-naphthoquinone (derivative S7). Our results indicate that derivatives S3, S5, S6 and S7 were non-toxic to the 3T3 fibroblast cell line. In scratch assays, derivatives S3 and S6, but not S5 or S7, stimulated the migration of fibroblasts. Compared with untreated diabetic mice, S3, S6 and S7 treatments accelerated wound closure. However, derivative S3 was optimal for the stimulation of epithelization, thereby increasing the number of keratinocyte layers and blood vessels, and reducing diffuse cellular infiltration, compared to derivatives S6 and S7. Our results suggest that novel 1,4-naphthoquinone derivatives promote fibroblast migration and accelerate wound closure under diabetic conditions.

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.

There is evidence that the constituents of essential oils from plants of the genus Croton, such as Croton argyrophyllus Kunth, can be used for anti-inflammatory, antiproliferative, antidiabetic and antitumor purposes. As this is a genus of plants widely used among the communities of the semiarid region of Brazil, the present study aimed to identify the chemical composition and analyze the cytotoxicity of the essential oil from C. argyrophyllus Kunth. The essential oil was obtained through hydrodistillation from fresh leaves (0.33% yield) and analyzed by gas chromatography–mass spectrometry/flame ionization detector (GC–FID). The cytotoxic concentration of the essential oil of C. argyrophyllus by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) test against the J774 macrophage was found to be 50 μg/mL. Twenty-five compounds were identified, representing 97.37% of the total oil, and the chemical profile was based on sesquiterpenes, with bicyclogermacrene (27.78%) its main constituent. ...

Previous studies on the genus Clusia have shown anti-inflammatory and antiproliferative effects of the leaf extracts, but its antinociceptive activity has never been characterized. In the present study, the antinociceptive activity of the hexane extract of the leaves of Clusia nemorosa G. Mey, called HECn, was examined. Antinociceptive activity was evaluated using acetic acid-induced writhing, formalin, and hot-plate tests. All experiments were carried out on male Swiss mice. The extract (1-400 mg·kg−1), given by intraperitoneal route (i.p.) 1 h prior to testing, produced a dose-dependent inhibition on the number of abdominal writhings, with an ID50 of 62 mg·kg−1. In addition, HECn was able to prevent the visceral pain induced by acetic acid in mice for at least 2 h. In the formalin test, HECn had no effect in the first phase, but produced an analgesic effect on the second phase with the inhibition of licking time. The HECn did not show a significant analgesic effect in the hot plate test. Pretreatment with yohimbine attenuated the antinociceptive effect induced by HECn in the writhing test. However, naloxone, atropine, or haloperidol did not affect antinociception induced by HECn in the writhing test. Together, these results indicate that the extract from the leaves of Clusia nemorosa produces antinociception in models of chemical pain through mechanisms that suggest participation of the adrenergic systems pathway.

Sabicea species are used in the Amazon for treatment of fever and malaria, which suggests that its chemical constituents may have some effect on pain and inflammation. Phytochemical analysis of the hexane fraction obtained from the crude ethanol extract from Sabicea grisea var. grisea Cham. & Schltdl (Rubiaceae), an endemic plant in Brazil, resulted in the isolation of octacosanol. This study investigated the antinociceptive and anti-inflammatory effects of the octacosanol in different experimental models. The crude ethanolic extract and hexane fraction obtained from the leaves of S. grisea produced an inhibition of acetic acid-induced pain. Moreover, octacosanol isolated from the hexane fraction produced a significant inhibition of pain response elicited by acetic acid. Pre-treatment with yohimbine, an alpha 2-adrenergic receptor antagonist, notably reversed the antinociceptive activity induced by octacosanol in the abdominal constriction test. Furthermore, mice treated with octacosanol did not exhibit any behavioral alteration during the hot plate and rota-rod tests, indicating non-participation of the supraspinal components in the modulation of pain by octacosanol with no motor abnormality. In the formalin test, octacosanol did not inhibit the licking time in first phase (neurogenic pain), but significantly inhibited the licking time in second phase (inflammatory pain) of mice. The anti-inflammatory effect of octacosanol was evaluated using carrageenan-induced pleurisy. The octacosanol significantly reduced the total leukocyte count and neutrophils influx, as well as TNF-α levels in the carrageenan-induced pleurisy. This study revealed that the mechanism responsible for the antinociceptive and anti-inflammatory effects of the octacosanol appears to be partly associated with an inhibition of alpha 2-adrenergic transmission and an inhibition of pathways dependent on pro-inflammatory cytokines. Finally, these results demonstrated that the octacosanol from the leaves of S. grisea possesses antinociceptive and anti-inflammatory activities, which could be of relevance for the pharmacological control of pain and inflammatory processes.

The present study aimed to elucidate the antinociceptive and anti-inflammatory properties of the methanol extract from the mycelium of the endophytic fungus Rhizoctonia sp. (MEMRh) in mice. The antinociceptive activity was assessed using the abdominal constriction, hot plate, and formalin tests. The anti-inflammatory activity was assessed using a murine model of paw edema. Intraperitoneal administration of MEMRh (0.1, 1, 10 and 100 mg/kg, i.p.) produced an inhibition of acetic acid-induced writhing in mice for at least 8 h. In addition, all doses tested of the methanol extract were able to prevent thermal nociception in the hot-plate test. Furthermore, treatment with MEMRh (10 mg/kg, i.p.) inhibited both the early and late phases of formalin-induced nociception. This antinociceptive effect exhibited by MEMRh in the formalin test was reversed by the systemic administration of naloxone. MEMRh produced inhibition in a carrageenan-induced edema model at a dose of 10 mg/kg. The same extract also displayed significant activity against a histamine- or PGE(2)-induced edema model. The experimental data demonstrated that MEMRh showed remarkable anti-inflammatory and antinociceptive activities. Further studies are warranted to define and isolate the active anti-inflammatory and antinociceptive components from this endophytic fungus, which may yield effective agents for the treatment of inflammatory disorders.

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.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.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.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.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.

In the present study, siaresinolic acid (siaresinol, SA) was isolated from the leaves of Sabicea grisea and studied to evaluate its antinociceptive and anti-inflammatory activity. The antinociceptive effect of SA was investigated in mice using different animal models to study pain. In the acetic acid-induced writhing test, intraperitoneal (i.p.) injection of SA (0.1, 1, and 10 mg/kg, i.p.) 1 h before a pain stimulus significantly reduced the nociceptive response (by 42.3, 68.2, and 70.9 %, respectively). Pretreatment with glibenclamide, but not with yohimbine, metoclopramide, ketanserin, or naloxone, restored the antinociceptive effect induced by SA in the writhing test, suggesting that the K(+)ATP channel pathway might be involved in its mechanism of action. In the formalin test, SA (1 mg/kg, i.p.) decreased licking time in the second phase only, thereby indicating an anti-inflammatory effect. In the hot plate test, there was no significant difference in nociceptive behavior. In the rota-rod test, it was verified that a high dose of SA (10 mg/kg, i.p.) did not affect the locomotor activity of mice. In the pleurisy model, induced by carrageenan, treatment with SA inhibited important events involved in inflammatory responses, namely leukocyte influx, plasma leakage, and increased inflammatory mediators (TNF-α, IL-1β, and chemokine CXCL1), in the pleural exudate. Additionally, SA itself was not cytotoxic when evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in macrophages cultured for 24 h at concentrations ranging from 1 to 200 μg/mL. These results suggest, for the first time, that SA attenuates nociceptive behavior through mechanisms involving receptors for ATP-dependent potassium channels, in addition to suppressing acute inflammatory responses.

This study aimed at synthesizing the carvacrol propionate (CP) and evaluating its pharmacological profile. CP was obtained from carvacrol and propionyl chloride through an esterification reaction. Male Swiss mice were treated with CP (25, 50, or 100 mg/kg). We evaluated the analgesic effect, mechanical hyperalgesia, and anti-inflammatory effect. Pre-treatment with CP inhibited (p

The present study was carried out to investigate the anti-inflammatory effect of the hexane extract of the leaves from Clusia nemorosa G. Mey, called HECn, using carrageenan-induced mice pleurisy and cotton pellet-induced mice granuloma. Additionally, the ability of HECn to affect both neutrophil migration as viability was investigated by use of the Boyden chamber assay and flow cytometry, respectively. The HECn significantly inhibited exudation, total leukocytes and neutrophils influx, as well as TNFα levels in carrageenan-induced pleurisy. However, the extract not suppressed the granulomatous tissue formation in the cotton pellet-induced granuloma test. Experiments performed in vitro revealed that HECn on human neutrophils inhibited a dose-dependent manner the CXCL1-induced neutrophil chemotaxis. Furthermore, HECn also inhibited the chemoattraction of human neutrophils induced by formyl-methionyl-leucyl-phenylalanine (fMLP), leukotriene B4 (LTB4) and platelet activating factor (PAF) in a Boyden chamber. However, this same treatment not was able to induce apoptosis. The results obtained in this study showed that the extract from leaves of C. nemorosa possess a potent inhibitory activity in acute model of inflammation, being the effects mediated, in part, by inhibition of neutrophil responsiveness. These results indicate that C. nemorosa could be a good source for anti-inflammatory compounds.