Topical Antiedematogenic Activity of the Essential Oil of Psidium brownianum Mart. (OEPB) in Murine Ear Edema Models.

Psidium brownianum Mart is reported in the literature by antinociceptive and antioxidant activities, indicating that this species' secondary metabolites might be used to control inflammatory processes. The present study aimed to characterize the topical antiedematogenic activity of the essential oil of Psidium brownianum Mart. (OEPB) in ear edema models by different inflammatory agents. Female Swiss mice (25-35 g) and Wistar albino rats (200-300 g) were used throughout tests (n=6/group) on acute or chronic edema models induced by single and multiple topical applications. The OEPB is administered topically pure or at a concentration of 100 or 200 mg/mL. The antiedematogenic mechanism of OEPB was analyzed by administering capsaicin, arachidonic acid, histamine, and phenol at the best effective dose (200 mg/mL). The results showed a significant reduction of edema-induced single (28.87 %) and multiple (50.13 %) applications of croton oil compared to the negative control group. Regarding potential mechanisms of action, OEPB (200 mg/mL) inhibited the development of edema triggered by capsaicin (29.95 %), arachidonic acid (22.66 %), phenol (23.35 %), and histamine (75.46 %), suggesting an interference with the histaminergic pathway. These results indicate that OEPB presents a topical antiedematogenic effect in acute and chronic murine models, possibly interfering with inflammatory pathways triggered by mediators such as histamine.

Perillyl Alcohol Promotes Relaxation in Human Umbilical Artery.

BACKGROUND: Perillyl alcohol (POH) is a monoterpenoid found in plant essential oils and has been shown to relax murine vessels, but its effect on human vessels remains poorly studied. OBJECTIVE: The study aimed to characterize the effect of POH on human umbilical arteries (HUA). METHODS: Rings of HUA were obtained from uncomplicated patients and suspended in an organ bath for isometric recording. The vasorelaxant effect of POH in HUA was evaluated on basal tone and electromechanical or pharmacomechanical contractions, and possible mechanisms of action were also investigated. RESULTS: POH (1-1000 µM) altered the basal tone of HUA and completely relaxed HUA rings precontracted with KCl (60 mM) or 5-HT (10 µM), obtaining greater potency in the pharmacomechanical pathway (EC50 110.1 µM), suggesting a complex interference in the mobilization of extra- and intracellular Ca2+. POH (1000 µM) inhibited contractions induced by BaCl2 (0.1-30 mM) in a similar way to nifedipine (10 µM), indicating a possible blockade of L-type VOCC. In the presence of potassium channel blockers, tetraethylammonium (1 mM), 4-aminopyridine (1 mM), or glibenclamide (10 µM), an increase in the EC50 value of the POH was observed, suggesting a modulation of the activity of BKCa, KV, and KATP channels. CONCLUSION: The data from this study suggest that POH modulates Ca2+ and K+ ion channels to induce a relaxant response in HUA.

Investigation of mechanisms of action involved in the antidepressant-like effect of Trans,trans-farnesol in mice.

This study aimed to investigate, through in vivo and biochemical methodologies, the effect of trans,trans-farnesol (12.5, 25, 50 or 100 mg/kg, p.o.) acute administration, adopting different behavioral and neurochemical parameters associated with an acute induced-depression model in mice. The initial results showed that, the oral treatment with trans,trans-farnesol, at the dose of 100 mg/kg induced a possible antidepressant-like effect in animals subjected to forced swim test (FST) and reserpine-induced akinesia. In addition, it was observed that the compound in question has an effect size and properties similar to imipramine (prototype of tricyclic antidepressants), but devoid of proconvulsant adverse effect. In biochemical assays, the pretreatment with trans,trans-farnesol, at a dose of 100 mg/kg (p.o.), decreased the hippocampal concentration of thiobarbituric acid reactive substances (TBARS) and restored striatal levels of noradrenaline and serotonin in mice subjected to FST. Altogether, these results suggest that trans,trans-farnesol showed a significant antidepressant-like effect, which seems to be mediated by the antagonism of muscarinic cholinergic receptors, reduction of oxidative stress and the modulation of noradrenaline and serotonin content in the central nervous system.

Enhancing the Antifungal Efficacy of Fluconazole with a Diterpene: Abietic Acid as a Promising Adjuvant to Combat Antifungal Resistance in Candida spp.

The increasing antifungal resistance rates against conventional drugs reveal the urgent need to search for new therapeutic alternatives. In this context, natural bioactive compounds have a critical role in antifungal drug development. Since evidence demonstrates that abietic acid, a diterpene found in Pinus species, has significant antimicrobial properties, this study aimed to evaluate the antifungal activity of abietic acid against Candida spp and its ability to potentiate the activity of fluconazole. Abietic acid was tested both individually and in combination with fluconazole against Candida albicans (CA INCQS 40006), Candida krusei (CK INCQS 40095), and Candida tropicalis (CT INCQS 40042). The microdilution method was used to determine the IC50 and the cell viability curve. Minimum Fungicidal Concentration (MFC) was determined by subculture in a solid medium. The plasma membrane permeability was measured using a fluorescent SYTOX Green probe. While the IC50 of the drugs alone ranged between 1065 and 3255 µg/mL, the IC50 resulting from the combination of abietic acid and fluconazole ranged between 7563 and 160.1 µg/mL. Whether used in combination with fluconazole or isolated, abietic acid exhibited Minimum Fungicidal Concentration (MFC) values exceeding 1024 µg/mL against Candida albicans, Candida krusei and Candida tropicalis. However, it was observed that the antifungal effect of fluconazole was enhanced when used in combination with abietic acid against Candida albicans and Candida tropicalis. These findings suggest that while abietic acid alone has limited inherent antifungal activity, it can enhance the effectiveness of fluconazole, thereby reducing antifungal resistance.

Vasorelaxant effect of (E,E)-farnesol in human umbilical vein ex vivo assays.

(E,E)-farnesol is a sesquiterpene acyclic alcohol produced by bacteria, protozoa, fungi, plants, and animals. The literature describes its applications in food, pharmaceutical, and cosmetic industries, and also in the pharmacological context with a vasorelaxant effect. However, its effects on human umbilical vessels remain poorly investigated. Thus, this study aims to investigate, in a new way, the vasorelaxant effect of (E,E)-farnesol in human umbilical veins (HUV) from healthy donors. Rings obtained from isolated HUV were suspended in an organ bath to record their isometric tension in different experimental sections. (E,E)-farnesol (1 µmol/L to 1 mmol/L) promoted vasorelaxant effect in venous preparations contracted by depolarization (KCl 60 mmol/L) or pharmacological agonism (5-HT 10 µmol/L), with EC50 values of 239.9 µmol/L and 424 µmol/L, respectively. In calcium-free solution, this effect was also observable. (E,E)-farnesol was able to suppress contractions evoked by CaCl2 and BaCl2 suggesting a blockade of voltage-dependent (especially L-type) calcium channels. The vasorelaxant efficacy and potency of (E,E)-farnesol were affected in the presence of tetraethylammonium (1 and 10 mmol/L), glibenclamide (10 µmol/L) and BaCl2 (1 mmol/L) indicating a possible involvement of potassium channels (BKCa, KATP and KIR) in this effect. Our data suggest that (E,E)-farnesol has a promising potential to be applicable as a vasodilator in hypertensive conditions in pregnancy that alter HUV reactivity.

Possible mechanisms involved in the neuroprotective effect of Trans,trans-farnesol on pilocarpine-induced seizures in mice.

This study aimed to investigate, through in vivo and in vitro methodologies, the effect of acute trans,trans-farnesol (12.5, 25, 50 or 100 mg/kg, p.o.) administration on behavioral and neurochemical parameters associated with pilocarpine-induced epileptic seizure (300 mg/kg, i.p.) in mice. The initial results showed that the compound in question presents no anxiolytic-like or myorelaxant effects, despite reducing locomotor activity in the animals at all doses tested. In addition, the lowest dose increased the latency to onset of the first epileptic seizure, and the time to death. In addition to decreasing the mortality percentage in mice submitted to the pilocarpine model. In this same model, pretreatment with the lowest dose of the compound decreased the hippocampal concentrations of thiobarbituric acid and nitrite, and partially restored striatal concentrations of noradrenaline, dopamine, and serotonin. Taken together, the results suggest that trans,trans-farnesol presents a central depressant effect which contributes to its antiepileptic action which, in turn, seems to be mediated by the antagonism of muscarinic cholinergic receptors, reduction of oxidative stress. and modulation of noradrenaline, dopamine and serotonin concentrations in the central nervous system.

Hypoglycemic, Hypolipidemic, and Anti-Inflammatory Effects of Beta-Pinene in Diabetic Rats.

Background: Diabetes is a metabolic disease linked to multiple comorbidities, such as low-grade inflammation. ß-pinene, a monoterpene commonly found in aromatic plants, is endowed with anti-inflammatory effect and this fact lead us to investigate the possible hypoglycemic, hypolipidemic and anti-inflammatory effects of the monoterpene in the alloxan-induced diabetes experimental model. Methods: Male Wistar rats (200-250 g) were treated orally with ß-pinene (25, 50, 100, and 200 mg/kg) or glibenclamide (5 mg/kg), for seven consecutive days. Diabetes was induced by alloxan (40 mg/kg) through the penile vein. On the seventh day of treatment, blood samples were collected for biochemical analysis. The anti-inflammatory effect of ß-pinene was evaluated using the carrageenan-induced paw edema model, followed by the carrageenan-induced peritonitis. Results: The treatment with ß-pinene decreased plasma glucose, triglyceride, VLDL, LDL, and HDL levels, when compared to those of the control group. In addition, the association ß-pinene 10 mg/kg + glibenclamide 2 mg/kg significantly decreased blood glucose, total cholesterol, and triglyceride level. Finally, oral treatment with ß-pinene reduced carrageenan-induced paw edema and leukocyte migration in the peritoneum. Taken together, our results indicate that ß-pinene shows hypoglycemic and hypolipemic effects, which may involve some common mechanisms of glibenclamide. Besides, the monoterpene presented an anti-inflammatory action in diabetic rats that needs further investigation in order to clarify such effect and its correlation with the alterations observed in plasma parameters of ß-pinene-treated diabetic rats.

Comparative analysis of chemical profiles and antioxidant activities of essential oils obtained from species of Lippia L. by chemometrics.

Due to the importance of diseases associated with oxidative stress, the search for natural antioxidants proves to be essential. This work aimed to compare the chemical composition and antioxidant potential of essential oils from the genus Lippia L. through chemometric analysis. The essential oils were characterized by gas chromatography coupled with mass spectrometry. Antioxidant potentials were determined by DPPH, ABTS, Deoxyribose and ß-carotene protection, Iron chelation and reduction methods. All data were related by multivariate analyzes. Essential oils showed low similar chemical compositions and no statistically significant relationship. These showed relevant antioxidant activity, especially for L. sidoides that obtained IC50 of 5.22 ± 0.08 µg/mL in ABTS capture. Multivariate analyzes showed the effectiveness of L. alba compounds to DPPH scavenging, Fe3+ reduction and ß-carotene protection, and L. gracilis components to deoxyribose protect. Thus, studies proving the antioxidant potential of Lippia compounds against oxidative stress and their use in food conservation are fundamental.

In Vitro and In Silico Inhibition of Staphylococcus aureus Efflux Pump NorA by α-Pinene and Limonene.

Since the discovery of the first antibiotics, bacteria have acquired a variety of resistance mechanisms, with efflux pump (EP) being the most prominent mechanism for intracellular targeting drugs. These proteins have become efficient mechanisms of resistance to antibiotics in species such as Staphylococcus aureus and, therefore, have been identified as promising therapeutic targets in antibacterial drug development. Accordingly, evidence suggests that monoterpenes can act as EP inhibitors and can be useful in circumventing bacterial resistance. This study aimed to evaluate the effectiveness of monoterpenes α-pinene and limonene as EP inhibitors against a strain of S. aureus expressing NorA protein. The minimum inhibitory concentration (MIC) against the 1199B strain of S. aureus, which carries genes encoding efflux proteins associated with antibiotic resistance to norfloxacin, was assessed through the broth microdilution method. The results obtained served as a subsidy for the analysis of the NorA pump inhibition with norfloxacin and ethidium bromide. Docking techniques, in silico, were used to evaluate the interaction of monoterpenes with NorA. Both monoterpenes showed no clinically effective antibacterial activity. Nevertheless, these compounds were found to decrease the MICs of ethidium bromide and norfloxacin indicating EP inhibition, which was confirmed by molecular docking analyses. In conclusion, α-pinene and limonene showed promising antibiotic-enhancing properties in S. aureus 1199B strain, indicating that monoterpenes can be used in targeted drug development to combat antibiotic resistance associated with EP expression.

Antibacterial and modulatory activities of ß-cyclodextrin complexed with (+)-ß-citronellol against multidrug-resistant strains.

The present study aimed to investigate the antibacterial and modulatory activities of (+)-ß-citronellol (ßCT), ß-cyclodextrin (ß-CD), and their complex ßCT/ß-CD and characterize them using infrared spectroscopy. Infrared spectra were recorded in the 750-4000 cm-1 region. The antibacterial effects of these compounds and their modulatory-antibiotic activities were determined using the minimum inhibitory concentration (MIC) test. Signatures of these pure compounds were detected in the infrared spectrum of the ßCT/ß-CD complex. The MIC of the ßCT/ß-CD complex against the tested strains was found to be 1024 µg/mL. The antagonistic and synergistic effects of these compounds were also observed using the modulation tests. ßCT or ß-CD alone did not exhibit any direct antibacterial activity. However, the ßCT/ß-CD complex in combination with gentamicin showed a synergistic effect against E. coli.

Pharmacological screening of the phenolic compound caffeic acid using rat aorta, uterus and ileum smooth muscle.

Caffeic acid is a phenolic compound widely found in commonly consumed foods such as pears, apples and coffee, and is pharmacologically known for its antioxidant, anti-inflammatory and anti-asthmatic properties. However, its relaxant activity in the aorta, uterus and ileum smooth muscle has not been investigated. This study aimed to comparatively evaluate the effect of caffeic acid on smooth muscle from different organs (aorta, uterus and ileum), and the contractions of this different organ were induced by different agonists. The organ bath technique was used, where the organs were placed in different cuvettes with 10 mL of Tyrode solution for 1 h to stabilize, then, myometrial, intestinal strip and aortic ring contractions were evoked using different contractile agonists (KCl 60 mM, PHE 0.1 µM, OT 10-2 IU/mL, CCh 10-6 M and BaCl2 0.1-30 mM); increasing concentrations of caffeic acid (0.03-7 mM) were administered in the experimental preparations. In the presence of KCl (60 mM), caffeic acid caused relaxations with the following EC50 values: 2.7 ± 0.26 mM/mL (aorta), 5.7 ± 0.71 mM/mL (uterus) and 2.1 ± 0.39 mM/mL (ileum). When in the presence of different agonists, PHE (0.1 µM) for the aorta, OT (10-2 IU/mL) for the uterus and CCh (10-6 M) for the ileum, caffeic acid caused relaxations with EC50 values of: 2.7 ± 0.31 mM/mL; 2.2 ± 0.34 mM/mL and 2.0 ± 0.28 mM/mL, respectively. The inhibitory effect of caffeic acid on serotonergic (aorta and uterus) and muscarinic receptors (uterus and ileum), as well as its possible involvement with L-type Ca2+ channels, was also observed. This study reports the pharmacological characterization of caffeic acid on smooth muscle from different organs, for which caffeic acid was more potent in the ileum. A diverse understanding of its performance as a possible therapeutic product is attributed to its relaxant effect.

Nootkatone Inhibits Acute and Chronic Inflammatory Responses in Mice.

Nootkatone (NTK) is a sesquiterpenoid found in essential oils of many species of Citrus (Rutaceae). Considering previous reports demonstrating that NTK inhibited inflammatory signaling pathways, this study aimed to investigate the effects of this compound in mice models of acute and chronic inflammation. Murine models of paw edema induced by carrageenan, dextran, histamine, and arachidonic acid, as well as carrageenan-induced peritonitis and pleurisy, were used to evaluate the effects of NTK on acute inflammation. A murine model of granuloma induced by cotton pellets was used to access the impact of NTK treatment on chronic inflammation. In the acute inflammation models, NTK demonstrated antiedematogenic effects and inhibited leukocyte recruitment, which was associated with decreased vascular permeability, inhibition of myeloperoxidase (MPO), interleukin (IL)1-ß, and tumor necrosis factor (TNF)-α production. In silico analysis suggest that NTZ anti-inflammatory effects may also occur due to inhibition of cyclooxygenase (COX)-2 activity and antagonism of the histamine receptor type 1 (H1). These mechanisms might have contributed to the reduction of granuloma weight and protein concentration in the homogenates, observed in the chronic inflammation model. In conclusion, NTK exerted anti-inflammatory effects that are associated with inhibition of IL1-ß and TNF-α production, possibly due to inhibition of COX-2 activity and antagonism of the H1 receptor. However, further studies are required to characterize the effects of this compound on chronic inflammation.

Antinociceptive activity of the Psidium brownianum Mart ex DC. leaf essential oil in mice.

Chronic pain management has several adverse effects and research looking for new and effective pain management drugs posing lower undesirable effects is necessary. Given the above, the pharmacological investigation of medicinal plants significantly contributes to the dissemination of plant-derived therapeutics. The aim of this study was to evaluate the antinociceptive activity of the Psidium brownianum Mart ex DC. leaf essential oil (PBEO) and the participation of the opioid pathway in this effect in mice. Swiss Mus musculus male mice were tested using acute nociception models (acetic acid induced abdominal contortions, formalin, capsaicin and hot plate tests). The possible myorelaxant action of the PBEO was tested using the rotarod test. The essential oil reduced animal nociception in chemical and heat models, with this action being devoid of a myorelaxant effect. Naloxone (2 mg/kg, intraperitoneally - i.p.) partially antagonized the PBEO activity, possibly acting via opioid receptors. The results obtained provide evidence that the traditional Psidium brownianum use may be effective for pain treatment.

Anxiolytic and antidepressant-like effects of Annona coriacea (Mart.) and caffeic acid in mice.

This research evaluated the anxiolytic and antidepressant-like effects of a hydroethanolic extract from the leaves of Annona coriacea (EHFAC) and caffeic acid (CA). Mice were intraperitoneally treated with saline, EHFAC (1, 10, 20 mg/kg) or CA (0.15 mg/kg) and subject to the elevated plus-maze, open field, rota-rod, forced swimming and reserpine-induced akinesia tests. Pro-convulsant and anticholinergic effects were also evaluated. EHFAC presented anxiolytic-like effect on the elevated plus-maze, which was partially reversed by flumazenil. A similar effect was observed with CA. In the forced swimming test, EHFAC and CA reduced the immobility time of mice; such effect was potentiated when EHFAC or CA were associated with imipramine, bupropion and fluoxetine. The antidepressant-like effect was reinforced as EHFAC partially reversed the reserpine-induced akinesia. In addition, a pre-treatment with EHFAC and CA did not decrease the latency to 1st seizure of animals that received a sub-convulsive dose of PTZ, nor reduced the intensity of oxotremorine-induced tremors. Taken together, the results indicate that EHFAC and CA have anxiolytic and antidepressant-like effects, which involve important neurotransmitter systems, such as GABAergic and monoaminergic ones, being devoid of side effects, commonly associated with classical psychotropic drugs.

Evaluation of the Antifungal Activity of the Licania Rigida Leaf Ethanolic Extract against Biofilms Formed by Candida Sp. Isolates in Acrylic Resin Discs.

Candida sp. treatment has become a challenge due to the formation of biofilms which favor resistance to conventional antifungals, making the search for new compounds necessary. The objective of this study was to identify the composition of the Licania rigida Benth. leaf ethanolic extract and to verify its antifungal activity against Candida sp. and its biofilms. The composition identification was performed using the ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) technique. The antifungal activity of extract and fluconazole against planktonic cells and biofilms was verified through the minimum inhibitory concentration (MIC) following biofilm induction and quantification in acrylic resin discs by reducing tetrazolic salt, with all isolates forming biofilms within 48 h. Six constituents were identified in the extract, and the compounds identified are derivatives from phenolic compounds such as flavonoids (epi) gallocatechin Dimer, epigallocatechin and gallocatechin, Myricetin-O-hexoside, Myricitrin, and Quercetin-O-rhamnoside. The extract reduced biofilm formation in some of the strains analyzed, namely C. tropicalis URM5732, C. krusei INCQS40042, and C. krusei URM6352. This reduction was also observed in the treatment with fluconazole with some of the analyzed strains. The extract showed significant antifungal and anti-biofilm activities with some of the strains tested.

Effects of the Hyptis martiusii Benth. leaf essential oil and 1,8-cineole (eucalyptol) on the central nervous system of mice.

The aim of this study was to characterize the central effects of the Hyptis martiusii leaf essential oil (OEHM) and 1,8-cineole (eucalyptol) using behavioral animal models. Gas chromatography coupled to mass spectrometry (GC/MS) was used to characterize the chemical compounds present in the OEHM. For the behavioral tests, female Swiss mice treated with the OEHM (25, 50, 100 and 200 mg/kg, i.p.) and 1,8-cineole (50 mg/kg, i.p.) were used and subjected to the following tests: open field, elevated cross maze, rotarod, sodium pentobarbital- or ethyl ether-induced sleep time, pentylenetetrazol-induced convulsions, haloperidol-induced catalepsy, and ketamine-induced hyperkinesia. GC/MS analysis identified 20 constituents with the majority of them being monoterpenes and sesquiterpenes, with eucalyptol (1,8-cineol), the major sample compound (25.93%), standing out. The results showed the OEHM (25, 50 100 and 200 mg/kg, i.p.) and its major compound (50 mg/kg, i.p.) reduced animal motility in the open field test, increased pentobarbital- and ethyl ether-induced sleep time, as well as death latency in the pentylenetetrazole-induced convulsion model. However, the tested compounds were devoid of anxiolytic-like and myorelaxant activity. In addition, the OEHM (100 and 200 mg/kg, i.p.) and 1,8-cineole (50 mg/kg, i.p.) potentiated haloperidol-induced catalepsy and reduced ketamine-induced hyperkinesia. Taken together, the results suggest the OEHM has important hypnotic-sedative and antipsychotic-like effects, which appear to be due to the monoterpene 1,8-cineole, the major compound identified in the essential oil.

Toxicological and pharmacologic effects of farnesol (C15H26O): A descriptive systematic review.

The objective of the present study was to perform a systematic review (SR) composed of preclinical and clinical studies which investigated the toxicological and pharmacologic effects of farnesol [Molecular formula: C15H26O; IUPAC: (3,7,11-Trimethyl-2,6,10-dodecatrien-1-ol]. This SR was performed according to PRISMA guidelines. Literature research was performed using PubMed, MEDLINE, Scopus and Web of Science databases using the descriptor combinations: "farnesol and pharmacological effect" and "farnesol and toxicology". The inclusion criteria used were original articles from preclinical and clinical studies investigating the pharmacological and toxicological effects of farnesol, published between January 1960 and December 2017 which were written in English, Portuguese and Spanish. Primary research identified 414 articles, from which 76 articles were selected for final analysis following the inclusion criteria. After grouping, 51.32 and 22.37% of the articles investigated the antimicrobial and antitumor effect, respectively. Methodological biases have been observed both in pre-clinical studies with non-human animals and in clinical trials, mainly in group allocation and blinding. This SR is the first study developed to compile the studies concerning the pharmacological and toxicological effects of farnesol. This study concludes that farnesol possesses different pharmacological and toxicological features, which permit its use as an active or a coadjuvant drug.

Phytochemical Analysis and Central Effects of Annona Muricata Linnaeus: Possible Involvement of the Gabaergic and Monoaminergic Systems.

Annona muricata Linnaeus (Annonaceae), popularly known as graviola, is used in folk medicine as both sedative and anticonvulsant. This study correlates the neurochemical profile with the behavioral effects of the hydroalcoholic extract from the leaves of Annona muricata (HLEAM) in mice, proposing to elucidate their mechanism of action on the central nervous system. Flavonoids and phenolic compounds were identified and quantified by High Performance Liquid Chromatography (HPLC) method. The acute toxicity (median lethal dose - LD50) was determined by probitos method using the percentage of mortality based on the Hippocratic screen. HLEAM (25, 50 and 100 mg/kg) was tested, intraperitoneally (i.p.), in models of sedation, anxiety, motor coordination, and seizures. The endogenous levels of dopamine, norepinephrine and DOPAC were assayed by reverse-phase HPLC with electrochemical detection. The HPLC analysis of the extract revealed the presence of flavonoids (quercetin, isoquercitrin, quercitrin, rutin, and kaempferol) and phenolics acids (gallic, chlorogenic, ellagic and caffeic acids). The LD50 was 1091.7 mg/kg and Hippocratic screening indicated central nervous system depressant effect. HLEAM presented sedative effects at doses of 25, 50, and 100 mg/kg, as well as anxiolytic and anticonvulsant effects at a dose of 100 mg/kg. In addition, these effects were partially reversed by flumazenil. The monoamines analysis by HPLC showed that HLEAM decreased the level of norepinefrine and dopamine in the mouse brain striatum. Thus, the results indicate a possible interaction of HLEAM with the GABAergic and monoaminergic systems, adding medicinal value to the popular use of the plant for the treatment of behavioral and neurological disorders.

Antiparasitic Activity and Essential Oil Chemical Analysis of the Piper Tuberculatum Jacq Fruit.

With the increase of neglected diseases such as leishmaniasis and Chagas disease, there was a need for the search for new therapeutic alternatives that reduce the harm caused by medicine available for treatment. Thus, this study was performed to investigate the antiparasitic activity of the essential oil from the fruits of Piper tuberculatum Jacq, against lines of Leishmania braziliensis (MHOM/CO/88/UA301), Leishmania infantum (MHOM/ES/92/BCN83) and Trypanosoma cruzi (LC-B5 clone). Before running protocols, an analysis of the chemical composition of essential oil was conducted, which presented monoterpenes and sesquiterpenes. As major constituents, ß-pinene and α-pinene were identified. Regarding to antiparasitic activity, the essential oil had an EC50 values of 133.97 µg/mL and 143.59 µg/mL against variations promastigotes of L. infantum and L. braziliensis, respectively. As for trypanocidal activity, the oil showed EC50 value of 140.31 µg/mL against epimastigote form of T. cruzi. Moreover, it showed moderate cytotoxicity in fibroblasts with LC50 value of 204.71 µg/mL. The observed effect may be related to the presence of terpenes contained in the essential oil, since it has its antiparasitic activity proven in the literature.

Caffeine-supplemented diet modulates oxidative stress markers and improves locomotor behavior in the lobster cockroach Nauphoeta cinerea.

The effects of caffeine supplementation is well documented in conventional animal models, however, in the lobster cockroaches Nauphoeta cinerea, they have not been reported. Thus, the aim of this study was to investigate the locomotor behavior and biochemical endpoints in the head of the nymphs of N. cinerea following 60 days exposure to food supplemented with 0, 0.5, 1.0, 2.5, 5.0 and 10.0 mg of caffeine/g of diet. The analysis of the locomotor behavior using the video-tracking software, Any-maze, for 12 min revealed that caffeine supplementation caused significant behavioral improvement. There was increase in distance travelled, velocity, frequency of rotation and turn angle (stereotypical behavior such as circling movements), and this was supported by the representative track plots of the path travelled by cockroaches in the open-field arena. In addition, caffeine supplementation markedly increased total thiol and non-protein thiol glutathione (GSH) levels in the heads of cockroaches, and this was in parallel with significant reduction of lipid peroxidation and free Fe(II) content. Taking together, our results indicate that long-term caffeine supplementation may exert preventive effects against oxidative stress and support the use of N. cinerea as an efficient alternative model to assess the efficacy of food molecules.