Lavandula angustifolia essential oil inhalation reduces mechanical hyperalgesia in a model of inflammatory and neuropathic pain: The involvement of opioid and cannabinoid receptors.

Lavandula angustifolia (LaEO) essential oil has been widely used by aromatherapy in the treatment of various clinical conditions, with evidence of its analgesic and anti-inflammatory potential. Our results demonstrate that sixty-five substances were identified in LaEO. Among the compounds found, the major ones were linalool (30.61%) and linalyl acetate (20.36%). We found that LaEO inhalation reduces mechanical hyperalgesia in conditions of chronic inflammatory and neuropathic pain. Furthermore, this effect seems to be mediated by peripheral and central opioid and cannabinoid 2 receptors. The findings of the present study suggests that the LaEO inhalation is effective on the chronic pain treatment.

CDK2 and Bcl-xL inhibitory mechanisms by docking simulations and anti-tumor activity from piperine enriched supercritical extract.

Supercritical fluid technologies offer an innovative method for food industry and drug discovery from natural sources. The aim of the study is to investigate the anti-tumor activity of piperine rich extract by supercritical fluid (SFE) from black pepper (Piper nigrum). In silico docking simulations predicted anti-tumor molecular mechanism and protein-piperine hydrophobic interactions, showing hydrogen bonds between piperine and residue Ser5 inside the ATP binding site in CDK2. Moreover, piperine interacts with peptide substrate residue Lys8 inside its binding site in Cyclin A molecule. Other predicted interaction showed piperine inside the hydrophobic groove of Bcl-xL. Confirming the docking simulation, in vitro assays with SFE (40 °C/30 MPa) showed cytotoxicity to MCF-7 cells (IC50 = 27.8 ±â€¯6.8 µg/ml) correlated to increased apoptosis. Balb/c mice-bearing Ehrlich Ascites Carcinoma (EAC) group that received the SFE (100 mg/kg/day) showed tumor growth inhibition (60%) and increased mice survival (50%), probably related to cell cycle arrest (G2/M) and increased apoptosis. In vivo treatments with SFE increased the expression of pro-apoptotic proteins (p53 and Bax), inhibited cell cycle proteins (CDK2, Cyclin A) and anti-apoptotic protein (Bcl-xL). Thus, confirming in silico predicted inhibitory interactions. These results clearly showed promising performance of the piperine-rich fraction recovered from black pepper, drawing attention to its use as complementary therapy for cancer.

In vivo antitumor activity of by-products of Passiflora edulis f. flavicarpa Deg. Rich in medium and long chain fatty acids evaluated through oxidative stress markers, cell cycle arrest and apoptosis induction.

Antiinflammatory and antitumor activity has been reported in Passiflora edulis (yellow passion fruit) nevertheless the intrinsic mechanisms of action are not fully elucidated. The present study aimeds to perform a comparison between the antitumor activity involving the crude extract (HCE) and the supercritical fluid extract with ethanol as co-solvent (SFEtOH) from P. edulis f. flavicarpa Deg. The in vitro cytotoxicity was evaluated in MCF-7 cells, while the in vivo antitumor activity was assessed in male Balb/c mice inoculated with Ehrlich carcinoma cells. SFEtOH exhibited higher antitumor activity compared to HCE. Wherein, SFEtOH showed an EC50 of 264.6 µg/mL against MCF-7 cells as well as an increased inhibition of tumor growth of 48.5% (p < 0.001) in male Balb/c mice, thereby promoting an increased mice lifespan to approximately 42%. Moreover, SFEtOH caused lipid (p < 0.001) and protein (p < 0.001) oxidation by increasing glutathione redox cycle activity while decreased the thioredoxin reductase activity (p < 0.001). SFEtOH also induced oxidative DNA damage in Ehrlich ascites carcinoma (EAC) cells leading to G2/M cycle arrest and has increased apoptotic cells up to 48.2%. These data suggest that the probable mechanisms of antitumor effect are associated to the lipid, protein and DNA damage, leading to cell cycle arrest and triggering apoptosis via mitochondrial pathway, should be probable due to the presence of medium and long chain fatty acids such as lauric acid.

The potent insulin secretagogue effect of betulinic acid is mediated by potassium and chloride channels.

Betulinic acid (BA) has been described as an insulin secretagogue which may explain its potent antihyperglycemic effect; however, the exact role of BA as an insulinogenic agent is not clear. The aim of this study was to investigate the mechanism of BA on calcium influx and static insulin secretion in pancreatic islets isolated from euglycemic rats. We found that BA triggers calcium influx by a mechanism dependent on ATP-dependent potassium channels and L-type voltage-dependent calcium channels. Additionally, the voltage-dependent and calcium-dependent chloride channels are also involved in the mechanism of BA, probably due to an indirect stimulation of calcium entry and increased intracellular calcium. Additionally, the downstream activation of PKC, which is necessary for the effect of BA on calcium influx, is involved in the full stimulatory response of the triterpene. BA stimulated the static secretion of insulin in pancreatic islets, indicating that the abrupt calcium influx may be a key step in its secretagogue effect. As such, BA stimulates insulin secretion through the activation of electrophysiological mechanisms, such as the closure of potassium channels and opening of calcium and chloride channels, inducing cellular depolarization associated with metabolic-biochemical effects, in turn activating PKC and ensuring the secretion of insulin.

Chemical composition, antioxidant and antibacterial activities of essential oils from leaves and flowers of Eugenia klotzschiana Berg (Myrtaceae)

ABSTRACT Many essential oils (EOs) of different plant species possess interesting antimicrobial effects on buccal bacteria and antioxidant properties. Eugenia klotzschiana Berg (pêra-do-cerrado, in Portuguese) is a species of Myrtaceae with restricted distribution in the Cerrado. The essential oils were extracted through the hydrodistillation technique using a modified Clevenger apparatus (2 hours) and chemically characterized by GC-MS. The major compounds were α-copaene (10.6 %) found in oil from leaves in natura, β-bisabolene (17.4 %) in the essential oil from dry leaves and α-(E)-bergamotene (29.9 %) in oil from flowers. The antioxidant activity of essential oils showed similarities in both methods under analysis (DPPH and ABTS˙+) and the results suggested moderate to high antioxidant activity. The antibacterial activity was evaluated by determining minimum inhibitory concentrations (MICs), using the microdilution method. MIC values below 400 µg/mL were obtained against Streptococcus salivarius (200 µg/mL), S. mutans (50 µg/mL), S. mitis (200 µg/mL) and Prevotella nigrescens (50 µg/mL). This is the first report of the chemical composition and antibacterial and antioxidant activities of the essential oils of E. klotzschiana. These results suggest that E. klotzschiana, a Brazilian plant, provide initial evidence of a new and alternative source of substances with medicinal interest.

Chemical composition, antioxidant and antibacterial activities of essential oils from leaves and flowers of Eugenia klotzschiana Berg (Myrtaceae).

Many essential oils (EOs) of different plant species possess interesting antimicrobial effects on buccal bacteria and antioxidant properties. Eugenia klotzschiana Berg (pêra-do-cerrado, in Portuguese) is a species of Myrtaceae with restricted distribution in the Cerrado. The essential oils were extracted through the hydrodistillation technique using a modified Clevenger apparatus (2 hours) and chemically characterized by GC-MS. The major compounds were α-copaene (10.6 %) found in oil from leaves in natura, ß-bisabolene (17.4 %) in the essential oil from dry leaves and α-(E)-bergamotene (29.9 %) in oil from flowers. The antioxidant activity of essential oils showed similarities in both methods under analysis (DPPH and ABTS˙+) and the results suggested moderate to high antioxidant activity. The antibacterial activity was evaluated by determining minimum inhibitory concentrations (MICs), using the microdilution method. MIC values below 400 µg/mL were obtained against Streptococcus salivarius (200 µg/mL), S. mutans (50 µg/mL), S. mitis (200 µg/mL) and Prevotella nigrescens (50 µg/mL). This is the first report of the chemical composition and antibacterial and antioxidant activities of the essential oils of E. klotzschiana. These results suggest that E. klotzschiana, a Brazilian plant, provide initial evidence of a new and alternative source of substances with medicinal interest.

High-Throughput Analysis of Lidocaine in Pharmaceutical Formulation by Capillary Zone Electrophoresis Using Multiple Injections in a Single Run.

This paper reports the development of a subminute separation method by capillary zone electrophoresis in an uncoated capillary using multiple injection procedure for the determination of lidocaine in samples of pharmaceutical formulations. The separation was performed in less than a minute leading to doing four injections in a single run. The cathodic electroosmotic flow contributed to reducing the analyses time. The background electrolyte was composed of 20 mmol L(-1) 2-amino-2-(hydroxymethyl)-1,3-propanediol and 40 mmol L(-1) 2-(N-morpholino)ethanesulfonic acid at pH 6.1. The internal standard used was benzylamine. Separations were performed in a fused uncoated silica capillary (32 cm total length, 23.5 cm effective length, and 50 µm internal diameter) with direct UV detection at 200 nm. Samples and standards were injected hydrodynamically using 40 mbar/3 s interspersed with spacer electrolyte using 40 mbar/7 s. The electrophoretic system was operated under constant voltage of 30 kV with positive polarity on the injection side. The evaluation of some analytical parameters of the method showed good linearity (r (2) > 0.999), a limit of detection 0.92 mg L(-1), intermediate precision better than 3.2% (peak area), and recovery in the range of 92-102%.

Ultrasound irradiation promoted efficient solvent-free lipase-catalyzed production of mono- and diacylglycerols from olive oil.

This work reports the enzymatic production of mono- and diacylglycerols under the influence of ultrasound irradiation, in a solvent-free system, with and without the presence of surfactants at a constant temperature of 65°C, glycerol to oil molar ratio of 2:1 and a commercial immobilized lipase (Novozym 435) as catalyst. For this purpose, two operation modes were adopted: the use of a sonotrode (ultrasonic probe), without agitation, varying reaction time, irradiation amplitude (25-45% of the total power) and type of surfactant, and a mechanically stirred reactor (600 rpm) under ultrasound irradiation in a water bath, testing different surfactants. Results show that very satisfactory MAG and DAG yields, above 50 wt.%, can be obtained without the use of surfactant, at mild irradiation power supply (∼130 W), with no important enzyme activity losses verified, in a relatively short reaction time (2h), and low enzyme content (7.5 wt.%). Also, reaction kinetic results show that contents of MAG+DAG as high as ∼65 wt.% can be achieved at longer times (6h), indicating a promising route for producing MAG and DAG using ultrasound irradiation.

Ultrasound-promoted synthesis of 3-trichloromethyl-5-alkyl(aryl)-1,2,4-oxadiazoles.

The alternative synthesis of 12 1,2,4-oxadiazoles using ultrasound irradiation from trichloroacetoamidoxime and acyl chlorides is reported. Seven of them are novel compounds. The 3-trichloromethyl-5alkyl(aryl)-1,2,4-oxadiazoles have been synthesised in better yields and shorter reaction times compared to the conventional method. This protocol can be applicable for preparation of 1,2,4-oxadiazoles containing aryl or alkyl groups attached at their C-5 side-chain.