Curcumin and n-acetylcysteine cocrystal produced with supercritical solvent: characterization, solubility, and preclinical evaluation of antinociceptive and anti-inflammatory activities.

Curcumin presents a promising anti-inflammatory potential, but its low water-solubility and bioavailability hinder its application. In this sense, cocrystallization represents a tool for improving physicochemical properties, solubility, permeability, and bioavailability of new drug candidates. Thus, the aim of this work was to produce curcumin cocrystals (with n-acetylcysteine as coformer, which possesses anti-inflammatory and antioxidant activities), by the anti-solvent gas technique using supercritical carbon dioxide, and to test its antinociceptive and anti-inflammatory potential. The cocrystal was characterized by differential scanning calorimetry, powder X-ray diffraction and scanning electron microscopy. The cocrystal solubility and antichemotaxic activity were also assessed in vitro. Antinociceptive and anti-inflammatory activities were carried out in vivo using the acetic acid-induced abdominal writhing and carrageenan-induced paw oedema assays in mice. The results demonstrated the formation of a new crystalline structure, thereby confirming the successful formation of the cocrystal. The higher solubility of the cocrystal compared to pure curcumin was verified in acidic and neutral pH, and the cocrystal inhibited the chemotaxis of neutrophils in vitro. In vivo assays showed that cocrystal presents increased antinociceptive and anti-inflammatory potency when compared to pure curcumin, which could be related to an improvement in its bioavailability.

Antichemotactic and Antifungal Action of the Essential Oils from Cryptocarya aschersoniana, Schinus terebinthifolia, and Cinnamomum amoenum.

The purpose of this work was to determine the chemical composition and evaluate the antichemotactic, antioxidant, and antifungal activities of the essential oil obtained from the species Cryptocarya aschersoniana Mez, Cinnamomum amoenum (Ness & Mart.) Kosterm., and Schinus terebinthifolia Raddi, as well as the combination of C. aschersoniana essential oil and terbinafine against isolates of dermatophytes. Allo-aromadendrene, bicyclogermacrene, and germacrene B were identified as major compounds in essential oils. The essential oil of C. aschersoniana shown 100 % inhibitory effect on leukocyte migration at the concentration of 10 µg/mL while S. terebinthifolia oil presented 80.1 % inhibitory effect at the same concentration. Only S. terebinthifolia oil possessed free-radical-scavenging activity which indicates its antioxidant capacity. The essential oils were also tested against fungal isolates of dermatophyte species (Trichophyton rubrum, Trichophyton mentagrophytes, Microsporum canis and Microsporum gypseum), resulting in MIC ranging from 125 µg/mL to over 500 µg/mL. C. aschersoniana oil combined with terbinafine resulted in an additive interaction effect. In this case, the essential oil may act as a complement to conventional therapy for the topical treatment of superficial fungal infections, mainly because it is associated with an anti-inflammatory effect.

Chemical analysis and in vitro antiviral and antifungal activities of essential oils from Glechon spathulata and Glechon marifolia.

CONTEXT: Glechon spathulata Benth. and Glechon marifolia Benth. (Lamiaceae, Mentheae) are aromatic plants used in traditional medicine for the treatment of viral infections. OBJECTIVE: The chemical composition and antiviral and antifungal activities of Glechon spathulata and Glechon marifolia essential oils were investigated. MATERIALS AND METHODS: The oils were obtained by hydrodistillation and analyzed by GC-FID and GC-MS. Anti-herpes virus (HSV-1) activity was examined in Vero cells by yield reduction assay, in doses of 0.0095% v/v and 0.039% v/v, for G. spathulata and G. marifolia oil, respectively. Antifungal activity was carried by the broth microdilution method, in oil concentrations that ranged from 5.2 to 500 µg/mL. RESULTS: ß-Caryophyllene (14.2% and 32.2% for G. spathulata and G. marifolia, respectively) and bicyclogermacrene (17.1% and 16.5%, respectively) were the major components of both oils. At noncytotoxic concentrations of the essential oils, the viral titer was reduced by up to 2 log10 for KOS and VR-733 strains. The antifungal activity was observed against Trichophyton rubrum (MIC 10-83 µg/mL) and Epidermophyton floccosum (MIC 83-500 µg/mL). The oil of G. spathulata exhibited activity against the three strains tested (KOS, VR733, and 29-R), whereas G. marifolia oil was active against two strains, KOS and VR733. DISCUSSION AND CONCLUSION: The chemical composition for G. spathulata and G. marifolia essential oils is very similar. The oil of G. spathulata can be promising as a new antifungal agent against dermatophytes. The findings add important information to the biological activity of Glechon species essential oils, specifically its antiviral and antidermatophytic properties.

Anti-Inflammatory Effects of Campomanesia xanthocarpa Seed Extract Obtained from Supercritical CO2.

Campomanesia xanthocarpa is a plant species traditionally used in the treatment of diabetes, fever, hypercholesterolemia, obesity, and urinary tract diseases. The anti-inflammatory effects of C. xanthocarpa leaves in mice were already known. Nevertheless, studies on the anti-inflammatory activity of its seeds are still lacking. The aim of this study was to investigate the anti-inflammatory activity and acute toxicity of C. xanthocarpa seed extract, obtained from supercritical CO2 extraction (SCCO2) at 40°C and 250 bar, in mice. GC/MS analysis revealed that ß-caryophyllene is the major compound present in the C. xanthocarpa SCCO2 extract. The extract (60 mg/kg, p.o.) significantly reduced the nociceptive behavior in the second phase of the formalin test and prevented the paw oedema induced by carrageenan up to 6 h after carrageenan injection. The extract (0.1-1 µg/mL) inhibited neutrophils migration induced by LPS from E. coli in vitro. This antichemostatic effect was comparable to the effect of indomethacin. Acute administration (2000 mg/kg, p.o.) of C. xanthocarpa SCCO2 extract caused no mice mortality, demonstrating that the extract is devoid of acute toxicity. These data suggest that C. xanthocarpa seeds present anti-inflammatory activity and represent a source of anti-inflammatory compounds.

Seizures of Clandestinely Produced Tablets in Santa Catarina, Brazil: The Increase in NPS from 2011 to 2017.

Ecstasy is the name given to a large group of substances known as "club drugs" traded in the form of tablets, powder and liquid that present a varied composition, including mainly 3,4-methylenedioxymethamphetamine (MDMA) and analogous substances, in addition to the growing presence of new psychoactive substances. Based on this, clandestinely produced tablets ("ecstasy tablets") seized by police in Santa Catarina in the period from 2011 to 2017 were analyzed. During the study period, 3472 seizures occurred, which resulted in total 498,443 tablets seized. Seventy nine substances were identified. In the year 2011, about 90% of the tablets contained MDMA. This number decreased to 66.6% in 2017. On the other hand, there was an increase in the number of tablets that mainly contained synthetic cathinones, as well as tryptamine and piperazine derivatives. Police seizures in the metropolitan region of Florianópolis and on the coast prevailed over the rest of the state.

Influence of Monoterpenes in Biological Activities of Nectandra megapotamica (Spreng.) Mez Essential Oils.

Investigating the influence of seasonal variations on biological activities is important for pharmacological studies and metabolic engineering. Therefore, this study was conducted to determine the variation of the chemical composition of essential oils obtained from Nectandra megapotamica leaves, collected at different stages of plant development, as well as its influence on the biological activities. A total of 38 compounds were identified that accounted for 97⁻99.2% of the chemical composition of the oils. Major differences were observed in the monoterpenic fraction, representing 5.1% of the compounds identified in the productive rest phase to 37.1% in the blooming phase. Bicyclogermacrene and germacrene D were the predominant compounds identified in the oil of all collections. Furthermore, limonene, ß-pinene, and spathulenol were identified predominantly in the samples of blooming and fruiting phases. The oils exhibited significant antichemotactic activity and different effects in scavenging the radical 2,2-diphenyl-1-picrylhydrazyl. Variations were also observed in the antifungal activity, with the minimum inhibitory concentrations ranging from 125 to 500 µg/mL. These results demonstrate the influence of monoterpenes, primarily limonene, α-pinene, and ß-pinene, on the bioactivities of the oil. Studies investigating the variations in the chemical composition of essential oil may offer a strategy to produce a compound or a group of compounds of interest to industries with a specific pharmacological focus.

Antifungal mechanism of action of Schinus lentiscifolius Marchand essential oil and its synergistic effect in vitro with terbinafine and ciclopirox against dermatophytes.

OBJECTIVES: The aim of this study was to evaluate the antifungal, antichemotactic and antioxidant activities of Schinus lentiscifolius essential oil, as well as its combined effect with terbinafine and ciclopirox, against dermatophytes. METHODS: Essential oil was analysed by GC-MS. The antifungal activity and the mechanism of action were determined by broth microdilution, sorbitol and ergosterol assays, as well as scanning electron microscopy. The checkerboard method was used for evaluating the interactions with commercial antifungal agents. The antioxidant and antichemotactic activities were measured using the DPPH and the modified Boyden chamber methods, respectively. KEY FINDINGS: Chemical analysis revealed the presence of 33 compounds, the primary ones being γ-eudesmol (12.8%) and elemol (10.5%). The oil exhibited 97.4% of antichemotactic activity and 37.9% of antioxidant activity. Antifungal screening showed effect against dermatophytes with minimum inhibitory concentration values of 125 and 250 µg/ml. Regarding the mechanisms of action, the assays showed that the oil can act on the fungal cell wall and membrane. Synergistic interactions were observed using the combination with antifungals, primarily terbinafine. CONCLUSIONS: Schinus lentiscifolius essential oil acted as a chemosensitizer of the fungal cell to the drug, resulting in an improvement in the antifungal effect. Therefore, this combination can be considered as an alternative for the topical treatment of dermatophytosis.

A valepotriate-enriched fraction from Valeriana glechomifolia Meyer inhibits leukocytes migration and nociception in formalin test in rodents

Abstract Previous pre-clinical studies demonstrated that a valepotriates enriched fraction from Valeriana glechomifolia F.G. Mey., Caprifoliaceae, was effective against lipopolysaccharide from Escherichia coli (LPS)-induced sickness behavior as well as significantly decreased the cortical expression of pro inflammatory cytokines interleukin-1β and tumor necrosis factor-α. Other studies revealed anti-inflammatory properties of V. wallichii and V. amurensis. These findings open up new perspectives for Valeriana genus pharmacology, once it has been commonly associated to sedative and anxiolytic properties. The aim of this study was to investigate the antichemotactic, antinociptive and anti-inflammatory activities of a valepotriate-enriched fraction obtained from aerial and subterranean parts of V. glechomifolia submitted to supercritical CO2 extraction. The biological activities were assessed by means of formalin test in CF1 mice and Wistar rat's leukocytes migration assay (modified Boyden chamber method). Valepotriate-enriched fraction (1, 10 and 30 mg/kg, p.o.) inhibited the nociceptive behavior in the late phase of the formalin test in a dose dependent manner. The effect of the valepotriate-enriched fraction highest dose was comparable with that of diclofenac 50 mg/kg (p.o.). Valepotriate-enriched fraction (0.1-1 µg/ml) inhibited the leukocyte migration induced by lipopolysaccharide from Escherichia coli in a concentration dependent manner. This antichemotatic effect was comparable with that of indomethacin (0.1-1 µg/ml) and better than diclofenac (1 µg/ml) effect. This study demonstrated for the first time that a valepotriate-enriched fraction obtained from V. glechomifolia display a peripheral anti-inflammatory like activity.

Essential oil composition and antichemotactic activity of stenachaenium benth species native to south Brazil / Composición y actividad antiquimiotaxica del aceite esencial de especies stenachaenium benth. nativas de sur de Brasil

Chemical composition of essential oils from four Stenachaenium species from South Brazil were established by gas chromatography coupled with mass spectrometry (GC/MS). The major compounds identified in the oil of S. megapotamicum were a coumarin derivative, 2H-1-benzopyran-2-one,7-(3-methylbutoxy) (24.0 percent), beta-bisabolene (12.8 percent) and thymol methyl ether (7.1 percent). The oil of S. adenanthum contained mainly pogostol (14.0 percent). S. riedelli oil showed significant presence of aliphatic compounds, with predominance of hexadecanoic acid in all samples (leaves, inflorescence and leaves collected during of inflorescence period). Hexadecanoic acid (23.8 percent) was also the main component in S. macrocephalum. Concerning antichemotactic activity, all the oil samples tested showed a significant leukocyte migration inhibition compared to chemotactic stimulant (lipopolysaccharide from Escherichia coli - LPS), at concentrations of 1 to 5 μg/mL, except for S. adenanthum. These results suggest that the essential oils of some Stenachaenium species could inhibit acute inflammatory process, because the migration of neutrophils occurs mainly in the early inflammatory process.

Se estableció la composición química de los aceites esenciales de cuatro especies de Stenachaenium del Sur de Brasil mediante cromatografía de gases acoplada a espectrometría de masas (CG/EM). Los compuestos mayoritarios identificados en el aceite de S. megapotamicum fueron: un derivado de cumarina, 2H-1-benzopiran-2-ona,7- (3-metilbutoxi) (24,0 por ciento), beta-bisaboleno (12,8 por ciento) y éter metil timol (7,1 por ciento). El aceite de S. adenanthum presentó principalmente pogostol (14,0 por ciento). El aceite de S. riedelli mostró una significativa presencia de compuestos alifáticos, con predominio de ácido hexadecanoico en todas las muestras (hojas, inflorescencias y hojas recolectadas durante del período de la inflorescencia). También el ácido hexadecanoico (23,8 por ciento) fue el principal componente en S. macrocephalum. En cuanto a la actividad antichemotaxica, todas las muestras de aceites ensayadas a concentraciones de 1 a 5 μg/ml, excepto para S. adenanthum, mostraron una inhibición significativa en la migración de leucocitos en comparación con agente quimiotáctico (lipopolisacárido de Escherichia coli – LPS). Estos resultados sugieren que los aceites esenciales provenientes de diferentes especies de Stenachaenium podrían inhibir procesos inflamatorios agudos, debido a que la migración de los neutrófilos se produce principalmente en el proceso inflamatorio temprano.