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.

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.

Vasodilation promoted by (E,E)-farnesol involving ion channels in human umbilical arteries.

Background: (E,E)-farnesol is a sesquiterpene alcohol derived from plants and animals that exhibits pharmacological properties in the cardiovascular system. However, its effects on human umbilical vessels remain unknown. Purpose: Thus, this study aims to characterize the vasodilatory effect of (E,E)-farnesol in human umbilical arteries (HUA). Study design: The tissue is obtained from pregnant women over 18 years of age, normotensive, and without prepartum complications. After collected, the tissue was segmented and dissected to remove Wharton's jelly and obtain the umbilical arteries segments. Methods: HUA segments were isolated and sectioned into rings that were subjected to isometric tension recordings in an organ bath. Results: (E,E)-farnesol (1 µmol/L to 1 mmol/L) promoted vasodilatory effect in HUA preparations, affecting basal tone, and inhibiting the electromechanical coupling induced by KCl 60 mmol/L with greater potency (EC50 225.3 µmol/L) than the pharmacomechanical coupling induced by 5-HT 10 µmol/L (EC50 363.5 µmol/L). In the absence of extracellular calcium, pharmacomechanical coupling was also abolished, and contractions induced by CaCl2 or BaCl2 were attenuated by (E,E)-farnesol indicating a possible direct inhibition of L-type VOCC as a mechanism of the vasodilatory effect. The vasodilator efficacy of (E,E)-farnesol on reduction of vasocontraction induced by the presence of tetraethylammonium (1 or 10 mmol/L), 4-aminopyridine (1 mmol/L) and glibenclamide (10 µmol/L) suggesting a possible influence of different potassium channels (BKCa, KV and KATP). Conclusion: These results suggest that (E,E)-farnesol may be a promising pharmacological candidate for obstetric hypertensive disorders.

The preeclampsia condition alters external potassium-evoked contraction of human umbilical vessels.

INTRODUCTION: Pre-eclampsia (PE) is a disease of high incidence in parturients, that adversely affects both mother and fetus. Although PE prevalence is high, there are few studies on literature describing its etiology or its mechanism of action. Thus, the aim of this study was to elucidate PE-induced alterations of contractile reactivity in umbilical vessels. METHOD: Segments of human umbilical artery (HUA) and human umbilical vein (HUV) from neonates of normotensive or PE parturients were obtained and contractile responses measured with a myograph. The segments were allowed to stabilize (2 h) under 1.0, 2.0 and 3.0 g force (gf) at pre-stimulation and, then, were stimulated with high isotonic K+ concentrations ([K+]o; 10-120 mM). RESULTS: All preparations responded to increases in isotonic K+ concentrations. In HUA and HUV of neonates of normotensive parturients, and in HUV of neonates of PE parturients, the contraction saturated at nearly 50 mM [K+]o, while in HUA of neonates of PE parturients, saturation occurred at 30 mM [K+]o. Additionally, several differences between contractile responses of HUA and HUV from neonates of normotensive parturients and those from neonates of parturients with PE were observed. PE alters the contractile response of the HUA and HUV to increased [K+]o, and its contractile modulation by the pre-stimulus basal tension. Moreover, in HUA of PE, reactivity is decreased for 2.0 and 3.0 gf basal tensions and increased for 1.0 gf; in the HUV of PE condition, it is increased for all basal tensions. DISCUSSION: In conclusion, PE promotes several alterations in HUA and HUV contractile reactivity, vessels in which important circulatory alterations are known to occur.

Pharmacological screening of species from the Lippia genus, content in terpenes and phenylpropanoids, and their vasorelaxing effects on human umbilical artery.

BACKGROUND: Naturally occurring bioactive compounds have a plethora of biological effects. OBJECTIVE: In this study, we examined a pharmacological screening of natural products on the human umbilical artery (HUA). METHODS: HUA preparations were used to follow contractions by KCl (60 mM) and tested at different concentrations (1-5000 µg/mL and µM) of the Lippia alba (EOLa) and Lippia origanoides (EOLo) essential oils, terpenes (citral, limonene perilic alcohol) and phenylpropanoids (eugenol, methyl eugenol). Discussion/Results: The reduction corresponded to approximately 100%, except for limonene (80±1.2 %). When evaluating the concentration of the natural product that promotes 50 % relaxation of the HUA contracted by KCL, EC50 values were: 424.3 µg/mL (EOLa); 468.7±6.7 µg/mL (EOLo); 264.2 ± 8.2 µM (citral); 677.8±5.4 µM (limonene); 186.3±6.4 µM (peryl alcohol); 986.4±7.9 µM (eugenol); and 279.1±4.4 µM (methyl-eugenol). Perillyl alcohol had a lower EC50 (consequently it has a higher pharmacological potency). CONCLUSION: The plant extracts have a promising vasorelaxing effect in HUAs, paving the way for future investigations: as applications in diseases related to these vessels, such as preeclampsia.

Effect of Lippia alba (Mill.) N.E. Brown Essential Oil on the Human Umbilical Artery.

Lippia alba is popularly known as lemon balm, with its essential oil (EO) cited for displaying antimicrobial, sedative, and vasorelaxant effects. Yet, its action on isolated human vessels has not been described in the literature. Thus, we evaluated the vasorelaxant effect of essential oil of L. alba (EOLa) on human umbilical arteries (HUA) isolated in organ baths. HUA rings were isolated, subjected to contractions induced by potassium chloride (KCl), serotonin (5-HT), or histamine (HIST) to record the isometric tension, and then treated with EOLa (30-1000 µg/mL). The EOLa showed a more prominent inhibitory effect on the pharmacomechanical coupling contraction via HIST with an EC50 value of 277.1 ± 8.5 µg/mL and maximum relaxant effect at 600 µg/mL. The addition of tetraethylammonium (TEA) or 4-aminopyridine (4-AP) in HUA preparations did not inhibit EOLa total relaxant effect at 1000 µg/mL. In the presence of gliblenclamide (GLI), the oil relaxed the HUA rings by 90.8% at maximum concentration. The EOLa was also investigated for its effects on voltage-operated calcium channels (VOCCs), where the HUA preincubation with this oil at 1000 µg/mL inhibited BaCl2 (0.1-30 mM)-induced contractions. This study demonstrates for the first time that EOla has a vasorelaxant effect on HUA and its particular blockade of VOCCs.

Characterization of the vasodilator effect of eugenol in isolated human umbilical cord arteries.

Eugenol (EUG) is a phenylpropanoid widely used in the food and cosmetic industries. It is commonly referred to in the literature by its biological activities such as antioxidant, anti-inflammatory, antimicrobial, and relaxing in organs of laboratory animals, especially in rodent vessels. However, its vasorelaxant potential in human tissue, has not been investigated. Thus, this study characterizes the vasodilatory effect of EUG in the human umbilical artery (HUA). HUAs were isolated, cleaned, sectioned (3-4 mm) and placed in an organ bath (10 mL Krebs Henseleit, 37 °C; and carbogenic mixture). EUG (100-1400 µM), obtained total relaxation of electromechanical contractions induced by KCl (60 mM), and pharmacomechanical contractions (30-1200 µM), induced by serotonin (10 µM) and by histamine (10 µM), showing statistically significant concentrations: 600 µM, 400 µM and 200 µM, and EC50 values: 759.8 ± 6.5 µM, 229.9 ± 7.9 and 279.0 ± 3.4 µM, respectively. EUG (1200 and 1400 µM) prevented the contraction promoted by BaCl2 (0.1-30 mM), similar to the effects of nifedipine (10 µM), sugesting the involvement of EUG in blocking VOCCs. In the presence of tetraethylammonium (10 µM), EUG (30-1200 µM) did not produce a total relaxation (88.6%), suggesting that an alternative pathway where potassium channels, may partially mediate EUG effect. In the presence of 4-aminopyridine (1 mM), glibenclamide (10 µM), and tetraethylammonium (1 mM), EUG relaxed HUAs 100%, although the pharmacological potency was statistically altered, demonstrating the participation of K+ channels (Kv, KATP, BKCa). Our data indicates that EUG has a vasorelaxant effect on HUAs, had a greater pharmacological potency in the serotoninergic pathway, showing effective participation of VOCCs and a partial modulation of K+ channels. These data suggest new possibilities for the use of EUG in human vascular dysfunctions, such as preeclampsia. More studies are necessary to confirm the safety and effectivity in future treatments.

Myorelaxant Effect of the Dysphania ambrosioides Essential Oil on Sus scrofa domesticus Coronary Artery and Its Toxicity in the Drosophila melanogaster Model.

PURPOSE: Alternative methods for the use of animals in research have gained increasing importance, due to assessments evaluating the real need for their use and the development of legislation that regulates the subject. The principle of the 3R's (replacement, reduction and refinement) has been an important reference, such that in vitro, ex vivo and cord replacement methods have achieved a prominent place in research. METHODS: Therefore, due to successful results from studies developed with these methods, the present study aimed to evaluate the myorelaxant effect of the Dysphania ambrosioides essential oil (EODa) using a Sus scrofa domesticus coronary artery model, and the toxicity of both the Dysphania ambrosioides essential oil and its major constituent, α-terpinene, against Drosophila melanogaster in toxicity and negative geotaxis assays. RESULTS: The EODa relaxed the smooth muscle of swine coronary arteries precontracted with K+ and 5-HT in assays using Sus scrofa domesticus coronary arteries. The toxicity results presented LC50 values of 1.546 mg/mL and 2.282 mg/mL for the EODa and α-terpinene, respectively, thus showing the EODa and α-terpinene presented toxicity to these dipterans, with the EODa being more toxic. CONCLUSIONS: Moreover, the results reveal the possibility of using the EODa in vascular disease studies since it promoted the relaxation of the Sus scrofa domesticus coronary smooth muscle.

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.

Relaxant Effect of Monoterpene (-)-Carveol on Isolated Human Umbilical Cord Arteries and the Involvement of Ion Channels.

Carveol is a monoterpene present in the structure of many plant products. It has a variety of biological activities: antioxidant, anticancer and vasorelaxation. However, studies investigating the effect of monoterpenoids on human vessels have not yet been described. Thus, the present study aimed to characterize the effect of (-)-carveol on human umbilical arteries (HUAs). HUA ring preparations were isolated and subjected to isometric tension recordings of umbilical artery smooth muscle contractions. (-)-Carveol exhibited a significant vasorelaxant effect on KCl and 5-HT-induced contractions, obtaining EC50 values of 344.25 ± 8.4 and 175.82 ± 4.05 µM, respectively. The participation of calcium channels in the relaxation produced by (-)-carveol was analyzed using vessels pre-incubated with (-)-carveol (2000 µM) in a calcium-free medium, where the induction of contractions was abolished. The vasorelaxant effect of (-)-carveol on HUAs was reduced by tetraethylammonium (TEA), which increased the (-)-carveol EC50 to 484.87 ± 6.55 µM. The present study revealed that (-)-carveol possesses a vasorelaxant activity in HUAs, which was dependent on the opening of calcium and potassium channels. These results pave the way for further studies involving the use of monoterpenoids for the vasodilatation of HUAs. These molecules have the potential to treat diseases such as pre-eclampsia, which is characterized by resistance in umbilical arteries.

Myorelaxant action of the Dysphania ambrosioides (L.) Mosyakin & Clemants essential oil and its major constituent α-terpinene in isolated rat trachea.

This study aimed to investigate the myorelaxant action of the Dysphania ambrosioides essential oil (EODa) and its major constituent α-terpinene on tracheal smooth muscle isolated from rats. In tracheal smooth muscle ex vivo, in organ baths, isometric contractions recordings were done in order to evaluated the effect of EODa (1-1000 µg/mL) and α-terpinene (1-3000 µg/mL) on the following parameters: basal tone, contractions evoked by potassium (KCl 60 mM), acetylcholine (ACh 10 µM) or serotonin (5-HT 10 µM). The EODa and its major constituent α-terpinene, did not statistically alter basal tone; however, they induced myorelaxant effects on top of contractions induced by KCl, ACh and 5-HT. EODa and α-terpinene also inhibited the contractions induced by barium in presence of High [K+] (80 mM). The data suggest that the relaxation induced by these agents is caused by the inhibition of L-type VGCC, inhibiting the inward Ca2+ current through these channels, but does not exclude the possibility of participation of other mechanisms. Results from this study also suggest the EODa, due to their efficacy on relaxation of the respiratory tract, posses a therapeutic potential as a antispasmodic agent for respiratory tract.

Pharmacological applications of farnesol (C15H26O): a patent review.

Introduction: Farnesol (C15H26O) is a sesquiterpene alcohol found in essential oils. This substance is reported to have different pharmacological activities such as antimicrobial, antitumor and antioxidant effects, as well as actions in different body systems.Areas covered: This study aimed to analyze pharmaceutical patents containing this substance in their formulations. Patent search was carried out through the WIPO (World Intellectual Property Organization), LatiPat and INPI (National Institute of Industrial Property) electronic banks using the following descriptors and combinations: 'farnesol', 'pharmaceutical product', 'pharmacology' and 'pharmacy'.Expert opinion: Primary research identified 54 patents, from which 17 were selected for the final analysis after applying the inclusion criteria. The selected patents referred to products presenting different pharmaceutical activities of interest such as the prevention and treatment of diseases affecting the dermis, central nervous and cardiovascular systems, diseases caused by different microorganisms and cancers, among others. A minority of the articles included in this review reported the type of farnesol isomer that was investigated, this becoming a major limitation for the development of future pharmaceutical products. With the completion of this study, farnesol presents itself as a potential agent with pharmacological application both in the prevention and treatment of different diseases.

Eucalyptol reduces airway hyperresponsiveness in rats following cigarette smoke-exposed.

BACKGROUND: Cigarette smoke is the major cause of airway inflammatory disease, including airway hyperresponsiveness. Eucalyptol (EUC), also named 1.8-cineole, is a monoterpenoid found in essential oil of medicinal plants, showing several biological effects. HYPOTHESIS/PURPOSE: Based in the eucalyptol protective activity in respiratory diseases as asthma, our hypothesis is that eucalyptol is able to reduce the airway hyperresponsiveness and the respiratory mechanic parameters in rats exposed to cigarette smoke. STUDY DESIGN: Wistar rats were divided into control and cigarettes smoke (CS) groups. CS group was daily subjected to cigarette smoke and treated by inhalation for 15 min/day with EUC (1 mg/mL) or vehicle during 30 days. After treatment, bronchoalveolar lavage (BAL) was collected to analyze the inflammatory profile, and tracheal rings were isolated for evaluation of the airway smooth muscle hyperresponsiveness. Lung function was analyzed in vivo. METHODS: The inflammatory profile was evaluated by optical microscopy performing total (Neubauer chamber) and differential leukocyte count (smear slides stained in H&E). The hyperresponsiveness was evaluated in tracheal rings contracted with potassium chloride (KCl) carbamoylcholine (CCh), or Barium chloride (BaCl2) in presence or absence of nifedipine. The lung function (Newtonian resistance-RN) was evaluated by bronco stimulation with methacholine (MCh). RESULTS: BAL from CS group increased the influx of leukocyte, mainly neutrophils and macrophages compared to control group. EUC reduced by 71% this influx. The tracheal contractions induced by KCl, CCh or BaCl2 were reduced by EUC in 59%, 42% and 26%, respectively. The last one was not different of nifedipine activity. Newtonian resistance (RN) was also reduced in 37% by EUC compared to CS group. CONCLUSION: EUC reduces the hyperresponsiveness and the airway inflammatory profile, recovering the lung function.

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.

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.

Tocolytic activity of the Lippia alba essential oil and its major constituents, citral and limonene, on the isolated uterus of rats.

The species Lippia alba (Mill.) N. E. Brown belongs to the Verbenaceae family. It is abundant and grows spontaneously throughout the Brazilian territory. Popularly known as "erva-cidreira", it is widely used because of its sedative, carminative and analgesic properties. The objective of this study was to investigate the mechanism of action of the L. alba essential oil (EOLa) and its major constituents citral and limonene, on isolated rat uterus muscle. To evaluate the EOLa, citral and limonene effect, cumulative concentrations curves for EOLa and citral (1-600 µg/mL) and for limonene (1-1200 µg/mL) were constructed from contractions of rat uterine strips under a 1 g tension. EOLa, citral and limonene dose-dependently relaxed myometrial preparations pre-contracted with 60 mM KCl, 10-2 IU/mL oxytocin, serotonin (10 µM), or ACh (10 µM). The results demonstrate that the EOLa, citral and limonene cause relaxation of the uterine smooth muscle. These results suggest that the relaxation induced by EOLa, citral and limonene is caused by inhibition of L-type VOCC, inhibiting the Ca2+ current through these channels, although other mechanisms of action are likely to contributing to relaxant activity. There was no involvement of K+ channels (BKca, KATP, KV) or cyclooxygenase on the relaxation promoted by EOLa. Then studies of the tocolytic effects of EOLa, citral and limonene may yield new insights into their therapeutic use.

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.

Effect of the Lippia alba (Mill.) N.E. Brown essential oil and its main constituents, citral and limonene, on the tracheal smooth muscle of rats.

The Lippia alba (Mill.) N.E. Brown (Verbenaceae) species, has effects sedative, analgesic and spasmolytic properties. This study had as its main objective to evaluate the essential oil of L. alba (EOLa) effect and that of its main constituents, citral and limonene, over tracheal smooth muscle from Wistar rats. EOLa, citral and limonene promoted relaxation of tracheal smooth muscle in contractions induced by potassium (60 mM K+), presenting an EC50 of 148 ±â€¯7 µg/mL for the EOLa, 136 ±â€¯7 µg/mL for citral and 581 ±â€¯7 µg/mL for limonene. In contractions induced by Acetylcholine (Ach; 10 µM) the EC50 for the EOLa and citral were of 731 ±â€¯5 µg/mL and 795 ±â€¯9 µg/mL, respectively. In preparations pre-incubated with 1000 µg/mL of the EOLa and citral, both agents were found to block the influx of BaCl2 by VOCCs. This study demonstrated that the EOLa and its main component citral present antispasmodic effect over tracheal smooth muscle of rats.

Uso de recursos naturais para o tratamento das doenças prevalentes na infância / Use of natural resources for treatment of childhood illness

Objetivo: identificar e realizar uma análise do uso de recursos naturais para tratamento de doenças prevalentes na infância em uma comunidade sob a perspectiva do Discurso do Sujeito Coletivo. Metodologia: estudo de abordagem qualitativa, onde adotou-se como estratégia metodológica a construção do Discurso do Sujeito Coletivo. Os dados foram coletados por meio de entrevista semiestruturada, sendo transcritos e para sua análise foi utilizado o Qualiquantisoft. Resultados: foram ao todo 54 informantes, as respostas ressaltaram a utilização de recursos naturais para o tratamento de doenças prevalentes na infância, sendo identificada nas ideias centrais e Discursos do Sujeito Coletivo encontrados. Evidenciou-se o uso dos recursos naturais no tratamento de doenças em crianças como alternativa ou complemento ao tratamento farmacológico, sendo expressada ainda grande confiabilidade nos resultados do seu uso. Conclusão: a utilização do Discurso do Sujeito Coletivo representou uma importante ferramenta para a obtenção dos dados, possibilitando assim uma análise mais fidedigna do conhecimento popular dos entrevistados.

Objective: identify and conduct a review of the use of natural resources for treatment of prevalent in childhood diseases in a community from the perspective of the Collective Subject Discourse. Methodology: study of qualitative approach, where as methodological strategy adopted the construction of the collective subject discourse. The data were collected through semi-structured interview being transcribed and for its analysis was used the Qualiquantisoft. Results: a total of 54 key informants, the responses highlight the use of natural resources for the treatment of prevalent in childhood diseases, being identified in the central ideas andthe Collective Subject Discoursefound. Showed the useof natural resources in the treatment of diseases in children as an alternative or complement to drug therapy, still expressed high confidence in the results of its use. Conclusion: the use of the collective subject discourse represented an important toolfor getting the data, thus enabling a more accurate analysis of the popular knowledge of respondents.

Anti-inflammatory and antiedematogenic activity of the Ocimum basilicum essential oil and its main compound estragole: In vivo mouse models.

The genus Ocimum are used in cooking, however, their essential oils are utilized in traditional medicine as aromatherapy. The present study was carried out to investigate the chemical composition and systemic anti-inflammatory activity of the Ocimum basilicum essential oil (EOOB) and its major component estragole, as well as its possible mechanisms of action. The Ocimum basilicum essential oil was obtained by hydrodistillation and analyzed by GC-MS. The anti-inflammatory action was verified using acute and chronic in vivo tests as paw edema, peritonitis, and vascular permeability and granulomatous inflammation model. The anti-inflammatory mechanism of action was analyzed by the participation of histamine and arachidonic acid pathways. The chemical profile analysis identified fourteen components present in the essential oil, within them: estragole (60.96%). The in vivo test results show that treatment with EOOB (100 and 50 mg/kg) and estragole (60 and 30 mg/kg) significantly reduced paw edema induced by carrageenan and dextran. The smallest doses of EOOB (50 mg/kg) and estragole (30 mg/kg) showed efficacy in the reduction of paw edema induced by histamine and arachidonic acid, vascular permeability inhibition and leukocyte emigration in the peritoneal fluid. Theses doses were capable of reducing the chronic inflammatory process. The results observed between the EOOB and estragole demonstrate efficacy in anti-inflammatory activity, however, the essential oil is more efficacious in the acute and chronic anti-inflammatory action. This study confirms the therapeutic potential of this plant and reinforces the validity of its use in popular medicine.