Monoterpenes and their derivatives as agents for cardiovascular disease management: A systematic review and meta-analysis.

BACKGROUND: Monoterpenes are one of the most studied plant's secondary metabolites, they are found abundantly in essential oils of aromatic plants. They also have a great range of pharmacological properties, such as antihypertensive, bradycardic, antiarrhythmic and hypotensive. In the face of the burden caused by cardiovascular disease (CVDs) worldwide, studies using monoterpenes to assess their cardiovascular effects have increased over the years. PURPOSE: This systematic review aimed to summarize the use of monoterpenes in animal models of any CVDs. METHODS: PubMed, SCOPUS, LILACS and Web of Science databases were used to search for articles that used monoterpenes, in any type of administration, to treat or prevent CVDs in animal models. The PRISMA guidelines were followed. Two independent researchers extracted main characteristics of studies, methods and outcomes. Data obtained were analyzed qualitatively and quantitatively. RESULTS: At the ending of the search process, 33 articles were selected for the systematic review. Of these, 17 articles were included in the meta-analysis. A total of 16 different monoterpenes were found for the treatment of hypertension, myocardial infarction, pulmonary hypertension, cardiac hypertrophy and arrhythmia. The main actions include hypotension, bradycardia, vasodilatation, antiarrhythmic, and antioxidant and antiapoptotic properties. From our data, it can be suggested that monoterpenes may be a significant source for new drug development. However, there is still a need to apply these knowledge into clinical research and a long path to pursue before putting them in the market. CONCLUSION: The variability of cardiovascular effects demonstrated by the monoterpenes highlighted them as a promising candidates for treatment or prevention of CVDs. Nevertheless, studies that investigate their biological sites of action needs to be further encouraged.

The use of terpenes and derivatives as a new perspective for cardiovascular disease treatment: a patent review (2008-2018).

INTRODUCTION: Terpenes are a class of secondary metabolites that can be found in a variety of animal and plants species. They are considered the most structurally diversified and abundant of all natural compounds. Several studies have shown the application of terpenes, such as carvacrol, linalool, and limonene in many pharmaceutical and medicinal fields, including cardiovascular disorders, the leading cause of death worldwide. AREAS COVERED: In this review, the authors outlined patents from the last 10 years relating to the therapeutic application of terpenes for the treatment and/or prevention of cardiovascular diseases found in different databases, emphasizing the possibility of these compounds becoming new drugs that may help to decrease the burden of these disorders. EXPERT OPINION: There has been a growing awareness over recent years of the therapeutic use of terpenes and their derivatives as new pharmaceutical products. Patents involving the use of terpenes have been especially important in the technological development of new strategies for the treatment of cardiovascular diseases by bringing new scientific knowledge into the pharmaceutical industry. Therefore, the development of biotechnologies using natural products should be encouraged in order to increase the variety of drugs available for the treatment of cardiovascular diseases.

Physico-chemical characterization and antibacterial activity of inclusion complexes of Hyptis martiusii Benth essential oil in ß-cyclodextrin.

Cyclodextrins (CDs) have been used as important pharmaceutical excipients for improve the physicochemical properties of the drugs of low solubility as the essential oil of Hyptis martiusii. This oil is important therapeutically, but the low solubility and bioavailability compromises your use. Therein, the aim of this study was to obtain and to characterize physico-chemically the samples obtained by physical mixture (PM), paste complexation (PC) and slurry complexation (SC) of the essential oil Hyptis martiusii (EOHM) in ß-CD, and to compare the antibacterial and modulatory-antibiotic activity of products obtained and oil free. The physicochemical characterization was performed by differential scanning calorimetry (DSC), thermogravimetry/derivative thermogravimetry (TG/DTG), scanning electron microscopy (SEM), X-ray diffraction (XRD) and Karl Fischer titration. Additionally, the antibacterial tests were performed by microdilution technique. Thus, it was observed that the PM method showed low complexing capacity, unlike PC and SC in which it was observed the formation of inclusion complexes. In addition, the second stage of the TG/DTG curves showed that SC was the best method inclusion with mass loss of 6.9% over the PC that was 6.0%. The XRD results corroborate with the results above suggesting the formation of new solid phase and the SEM photomicrographs showed the porous surface of the samples PC and SC. The essential oil alone demonstrated an antibacterial and modulatory effect against the S. aureus and the Gram negative strain, respectively. However, the ß-CD and the inclusion complex did not demonstrate any biological activity in the performed antibacterial assays.

Natural products assessed in animal models for orofacial pain – a systematic review

ABSTRACT Orofacial pain is related to tissues of the head, face, neck and all the intraoral structures; it is rather debilitating to the patient and also difficult to treat. There are relatively few studies dedicated to the use of natural products to alleviate orofacial pain in preclinical experiment models (performed in experimental animals which provide support for clinical trials). Main objectives of the present systematic review summarize the studies on natural products assessed in animal models for orofacial pain seeking to give evidence to future development of new pharmaceutical products to manage the orofacial pain. Our review includes a thorough search of literature using the terms of orofacial pain, facial pain, medicinal plants and natural products. This search was performed using to retrieve English language articles in Medline-PubMed, Scopus and Web of Science. A total of eighteen studies were included in our survey for the inclusion criteria. Firstly, this review identified 210 citations from electronic search, after removal of duplicates and screening for relevant titles and abstracts, a total of eighteen articles were selected to the inclusion criteria established. Our findings suggest that natural products can be a promising or a trump tool for the development of new drugs to treat orofacial pain conditions, but the researchers that deal with experimental preclinical trials of new drugs (including natural products or synthetic drugs) for orofacial pain conditions urgently need to show translational evidence (with clinical approach) of these compounds.

Phytochemical screening and analgesic profile of the lyophilized aqueous extract obtained from Chrysobalanus icaco leaves in experimental protocols.

CONTEXT: Chrysobalanus icaco L. (Chrysobalanaceae) has been used for the treatment of abdominal pain and cramps. OBJECTIVE: Assess the chemical and pharmacological profile of the lyophilized aqueous extract from C. icaco leaves (AEC). MATERIALS AND METHODS: Chromatographic methods were used to assess compounds from AEC. Mice were treated with vehicle (control group) or AEC (100, 200 or 400 mg/kg, p.o.) (group with 7-8 mice) and the analgesic profile was assessed employing the acetic acid-induced writhing, formalin, hot plate tests and hyperalgesia induced by carrageenan (CG) or tumour necrosis factor-alpha. The animal motor performance was assessed using rota-rod and grip strength tests. RESULTS: The chromatographic profile of AEC demonstrated the presence of terpenoid compounds. The acute pretreatment with AEC, at all doses, produced a significant (p < 0.01) inhibition of painful bahaviour (11.4 ± 3.6; 10.3 ± 2.8; 11.3 ± 2.2) when compared to the control group (24.7 ± 4.7) in acetic acid-induced writhing test. In the formalin test, AEC were effective in the second phase (p < 0.01) (57.2 ± 10.3; 56.3 ± 9.2; 54.7 ± 8.9) when compared to control group (121.9 ± 18.5). No response was observed in the hot plate test. The higher dose of AEC produced a significant (p < 0.01 or p < 0.05) inhibitory effect on the mechanical hyperalgesia test. AEC did not affect the motor performance of the mice. DISCUSSION: The terpenoids from AEC are known for its analgesic and anti-inflammatory properties. So, these results corroborate the experiments using the AEC in inflammatory pain protocols. CONCLUSION: Our results suggest that AEC act against inflammatory pain.

Docking, characterization and investigation of ß-cyclodextrin complexed with citronellal, a monoterpene present in the essential oil of Cymbopogon species, as an anti-hyperalgesic agent in chronic muscle pain model.

BACKGROUND: Citronellal (CT) is a monoterpene with antinociceptive acute effect. ß-Cyclodextrin (ßCD) has enhanced the analgesic effect of various substances. HYPOTHESIS/PURPOSE: To evaluate the effect of CT both complexed in ß-cyclodextrin (CT-ßCD) and non-complexed, in a chronic muscle pain model (CMP) in mice. STUDY DESIGN: The complex containing CT in ßCD was obtained and characterized in the laboratory. The anti-hyperalgesic effect of CT and CT-ßCD was evaluated in a pre-clinical in vivo study in a murine CMP. METHODS: The complex was characterized through differential scanning calorimetry, derivative thermogravimetry, moisture determination, infrared spectroscopy and scanning electron microscopy. Male Swiss mice were pre-treated with CT (50mg/kg, po), CT-ßCD (50mg/kg, po), vehicle (isotonic saline, po) or standard drug (tramadol4 mg/kg, ip). 60 min after the treatment and then each 1h, the mechanic hyperalgesia was evaluated to obtain the time effect. In addition, the muscle strength using grip strength meter and hyperalgesia were also performed daily, for 7 days. We assessed by immunofluorescence for Fos protein on brains and spinal cords of mice. The involvement of the CT with the glutamatergic system was studied with molecular docking. RESULTS: All characterization methods showed the CT-ßCD complexation. CT-induced anti-hyperalgesic effect lasted until 6h (p <0.001) while CT-ßCD lasted until 8h (p <0.001vs vehicle and p <0.001vs CT from the 6th h). CT-ßCD reduced mechanical hyperalgesia on all days of treatment (p <0.05), without changing muscle strength. Periaqueductal gray (p <0.01) and rostroventromedular area (p <0.05) showed significant increase in the Fos protein expression while in the spinal cord, there was a reduction (p <0.001). CT showed favorable energy binding (-5.6 and -6.1) to GluR2-S1S2J protein based in the docking score function. CONCLUSION: We can suggest that ßCD improved the anti-hyperalgesic effect of CT, and that effect seems to involve the descending pain-inhibitory mechanisms, with a possible interaction of the glutamate receptors, which are considered as promising molecules for the management of chronic pain such as CMP.

A systematic review of medicinal plants used for weight loss in Brazil: Is there potential for obesity treatment?

ETHNOPHARMACOLOGICAL RELEVANCE: Obesity is a pandemic disease and its prevalence is still increasing. Moreover, it has important costs to public health. In Brazil, many plants are used for weight loss by overweight or obese people, but there is a lack of scientific basis for this practice. Many ethnobotanical studies aiming to characterize this usage have been published, but they are still limited by the region considered and the diversity of the popular knowledge. AIM OF THE STUDY: The present study was undertaken to systematically review the ethnobotanical surveys regarding the species utilized to reduce body weight in overweight or obese people in Brazil. METHODS: Ethnobotanical surveys related to this usage and performed in Brazilian regions were systematically found in MEDLINE, LILACS and Scopus. RESULTS: Thirty-three studies were included in this review. Fifty species were popularly utilized to lose weight. The most cited species were Baccharis trimera (Less.) DC, Annona muricata L. and Hancornia speciosa Gomes. Camellia sinensis (L.) Kuntze and Hibiscus sabdariffa L. were also cited and are supported by either animal or human investigations that indicate some beneficial activity against obesity. However, for the majority of species cited in the included studies, there is no scientific basis that assures the biological effects of this usage. Many studies have demonstrated important effects of these plants on glycemia, serum lipid levels or body weight control in non-obese conditions, which is not sufficient to recommend the use of these plants to reduce body weight in overweight or obese people. CONCLUSIONS: Although many plants are popularly used to reduce weight in overweight or obese people in Brazil, there is little scientific evidence corroborating its usage. Based on the ethnobotanical data presented, this review indicates the plants that should be considered for scientifically controlled studies devoted to investigating their effects on obesity.

Preparation, Characterization, and Pharmacological Activity of Cymbopogon winterianus Jowitt ex Bor (Poaceae) Leaf Essential Oil of ß-Cyclodextrin Inclusion Complexes.

This study aimed to evaluate the orofacial antinociceptive effect of the Cymbopogon winterianus essential oil (LEO) complexed in ß-cyclodextrin (LEO-CD) and to assess the possible involvement of the central nervous system (CNS). The LEO was extracted, chromatographed, and complexed in ß-cyclodextrin. The complex was characterized by differential scanning calorimetry (DSC) and thermogravimetry derivative (TG/DTG). Male Swiss mice (2-3 months) were treated with LEO-CD (50-200 mg/kg, p.o.), vehicle (distilled water, p.o.), or standard drug (i.p.) and subjected to the orofacial nociception formalin-, capsaicin-, and glutamate-induced. After the formalin test, the animals were perfused and the brains subjected to immunofluorescence for Fos. The rota-rod test (7 rpm/min) was carried out. Geraniol (37.57%) was the main compound of LEO. DSC and TG/DTG proved the complexation. The orofacial nociceptive behavior was significantly (p < 0.05) reduced. The number of Fos-positive cells was significantly changed in the dorsal raphe nucleus (p < 0.01), locus coeruleus (p < 0.001), trigeminal nucleus (p < 0.05), and trigeminal thalamic tract (p < 0.05). LEO-CD did not cause changes in motor coordination in the rota-rod test. Thus, our results suggested that LEO-CD has an orofacial antinociceptive profile, probably mediated by the activation of the CNS without changing the motor coordination.

Physicochemical characterization and analgesic effect of inclusion complexes of essential oil from Hyptis pectinata L. Poit leaves with ß-cyclodextrin.

The formation of inclusion complexes of Hyptis pectinata essential oil (EOHP), with potent activities such as anti-nociceptive, anti-inflammatory, among others, with ß -cyclodextrin (ß-CD), was obtained by slurry (SC) and paste procedures (PC). The gas chromatography coupled to the mass spectrometry (GC/MS) analysis demonstrated a total of 36.4% monoterpenes and 63.6% sesquiterpenes in the EOHP. The major components of EOHP were identified as (E)- caryophyllene (54.07%). The analysis of samples (PM, PC and SC) by GC/MS involved the surface and the total extracted oils. The GC/MS results suggested important differences between in SC and PC methods indicating the complexation of mono and sesquiterpenoids in different ratios. Furthermore, the thermal analysis techniques suggests the complexation, especially in SC, which show a thermogravimetry/derivative thermogravimetry (TG/DTG) peak at 140-270ºC, probably related to oil loss. Scanning electron microscopy (SEM) images showed reduction size of the samples mainly in the SC product. Additionally, EOHP/ ß-CD improves pharmacological profile of EOHP alone in formalin-induced pain protocol in mice.

A systematic review of the wound-healing effects of monoterpenes and iridoid derivatives.

The search for more effective and lower cost therapeutic approaches for wound healing remains a challenge for modern medicine. In the search for new therapeutic options, plants and their metabolites are a great source of novel biomolecules. Among their constituents, the monoterpenes represent 90% of essential oils, and have a variety of structures with several activities such as antimicrobial, anti-inflammatory, antioxidant and wound healing. Based on that, and also due to the lack of reviews concerning the wound-healing activity of monoterpenes, we performed this systematic review-which provides an overview of their characteristics and mechanisms of action. In this search, the terms "terpenes", "monoterpenes", "wound healing" and "wound closure techniques" were used to retrieve articles published in LILACS, PUBMED and EMBASE until May 2013. Seven papers were found concerning the potential wound healing effect of five compouds (three monoterpenes and two iridoid derivatives) in preclinical studies. Among the products used for wound care, the films were the most studied pharmaceutical form. Monoterpenes are a class of compounds of great diversity of biological activities and therapeutic potential. The data reviewed here suggest that monoterpenes, although poorly studied in this context, are promising compounds for the treatment of chronic wound conditions.

Citronellol reduces orofacial nociceptive behaviour in mice - evidence of involvement of retrosplenial cortex and periaqueductal grey areas.

Citronellol (CT) is a monoterpenoid alcohol present in the essential oil of many medicinal plants, such as Cymbopogon citratus. We evaluated the antinociceptive effects of CT on orofacial nociception in mice and investigated the central pathway involved in the effect. Male Swiss mice were pretreated with CT (25, 50 and 100 mg/kg, i.p.), morphine (5 mg/kg, i.p.) or vehicle (saline + tween 80 0.2%). Thirty minutes after the treatment, we injected formalin (20 µl, 2%), capsaicin (20 µl, 2.5 µg) or glutamate (40 µl, 25 µM) into the right limb. For the action in the CNS, ninety minutes after the treatment, the animals were perfused, the brains collected, crioprotected, cut in a criostate and submitted in an immunofluorescence protocol for Fos protein. CT produced significant (p < 0.01) antinociceptive effect, in all doses, in the formalin, capsaicin and glutamate tests. The immunofluorescence showed that the CT activated significantly (p < 0.05) the olfactory bulb, the piriform cortex, the retrosplenial cortex and the periaqueductal grey of the CNS. Together, our results provide first-time evidence that this monoterpene attenuates orofacial pain at least, in part, through an activation of CNS areas, mainly retrosplenial cortex and periaqueductal grey.

Citronellol, a monoterpene alcohol, reduces nociceptive and inflammatory activities in rodents.

We describe the antinociceptive and anti-inflammatory properties of citronellol (CT) in rodents. CT, a monoterpene alcohol, is a naturally occurring monoterpene compound prevalent in essential oils of various aromatic plant species, such as Cymbopogon citratus. In mice, when evaluated against acetic-acid-induced abdominal writhing, CT (25, 50 and 100 mg/kg, i.p.) reduced (P < 0.001) the amount of writhing compared to the control group. In the formalin test, CT also significantly inhibited both the early (neurogenic pain) and the late (inflammatory pain) phases of formalin-induced licking (P < 0.001). When assessed in a thermal model of pain, CT (100 mg/kg, i.p.) caused a significant increase (P < 0.05) in the latency response on the hot-plate test. Such results were unlikely to be caused by motor abnormality. The anti-inflammatory activity of CT was investigated through carrageenan-induced pleurisy in mice. Pretreatment with CT was able to inhibit both neutrophil infiltration and the increase in TNF-α level in the exudates from carrageenan-induced pleurisy. In in vitro experiments, CT (1 and 100 µg/ml) also decreased nitric oxide production by LPS-stimulated macrophage. Together, these results indicate that CT is effective as an analgesic compound in various pain models, with its action probably mediated by the inhibition of peripheral mediators as well as central inhibitory mechanisms that could be related to its strong antioxidant effect observed in vitro.

Antinociceptive and anti-inflammatory effects of Caesalpinia pyramidalis in rodents

Caesalpinia pyramidalis Tul., Fabaceae, is a plant with an anti-inflammatory activity that is used in folk medicine. To evaluate the mechanism of action of this plant, studies were performed on its antinociceptive and anti-inflammatory properties using an ethanol extract (EE) made from the inner bark. Oral treatment of mice with the EE (100, 200, and 400 mg/kg) decreased their acetic acid-induced abdominal writhes (p<0.001) and their formalin-induced paw licking in both the first and second phases (p<0.001). This treatment increased the reaction time of mice on the hot-plate test (400 mg/kg, p<0.05); however, it did not alter their performance on the Rotarod performance test. The carrageenan-induced paw edema in the rats and the leukocyte migration into the peritoneal cavity of the mice were also reduced by the EE given at a dose of 400 mg/kg (p<0.05). In addition, the EE (100-400 mg/kg, v.o.) did not alter the arterial pressure of non-anesthetized rats. In conclusion, the EE of C. pyramidalis shows antinociceptive and anti-inflammatory activities in rodents, supporting the usage of this plant to treat various inflammatory diseases for which it has traditionally been used.

Cardiovascular effects of monoterpenes: a review

The monoterpenes are secondary metabolites of plants. They have various pharmacological properties including antifungal, antibacterial, antioxidant, anticancer, anti-spasmodic, hypotensive, and vasorelaxant. The purpose of this research was to review the cardiovascular effects of monoterpenes. The data in this resarch were collected using the Internet portals Pubmed, Scopus, and ISI Web of Knowledge between the years 1987 and 2010. In the study 33 monoterpenes were included, which were related to each of the thirteen individual words: artery, cardiovascular, heart, myocyte, vasorelaxant, vessel, hypotension, hypotensive, cardiomyocyte, ventricular, vasodilatory, aorta, and aortic. The research utilized 22 articles published mainly in the journals Phytomedicine, Fundamental Clinical Pharmacology, Planta Medica, Life Science, European Journal of Pharmacology, and Brazilian Journal of Medical and Biological Research. Of the 33 monoterpenes studied surveyed, sixteen of them had already been studied for their effects on the cardiovascular system: carvacrol, citronellol, p-cymene, eucalyptol (1,8-cineole), linalool, menthol, myrtenal, myrtenol, α-pinene, rotundifolone (piperitenone oxide), sobrerol, thymol, α-limonene, α-terpinen-4-ol, α-terpineol, and perillyl alcohol. The main effects observed were vasorelaxation, decreased heart rate and blood pressure. This review showed that the monoterpenes may be considered promising agents for prevention or treatment of diseases of the cardiovascular system.

Assessment of antinociceptive and anti-inflammatory activities of Porophyllum ruderale (Jacq.) Cass., Asteraceae, aqueous extract

The present work investigated the antinociceptive and antiinflammatory activities of the Porophyllum ruderale (Jacq.) Cass., Asteraceae, aqueous extract (PRAE). For this purpose, acetic acid writhing, paw licking induced by formalin, hot-plate and pleurisy tests were performed. The doses of 100, 200 and 400 mg/kg (p.o.) significantly inhibited the writhing 63.4, 89.6 and 94.8 percent, respectively, in comparison with control group. The lick of the paw 1st phase was reduced at the dose of 400 mg/ kg (24.9 percent), while the 2nd phase had reduction at doses 200 and 400 mg/ kg (23.1 and 34.4 percent), respectively. The PRAE inhibited the carrageenaninduced neutrophil migration to the peritoneal cavity in a higher dose (p<0.05). Taken together, our results suggest that the PRAE can constitute target potential for use in therapies of the pain and inflammation.

Chemical composition and cardiovascular effects induced by the essential oil of Cymbopogon citratus DC. Stapf, Poaceae, in rats / Composição química e efeitos cardiovasculares do óleo essencial de Cymbopogon citratus DC. Stapf, Poaceae, em ratos

Cymbopogon citratus DC. Stapf, Poaceae, is used in the folk medicine for hypertension treatment. This work investigated the chemical composition and cardiovascular effects in rats of C. citratus essential oil (EOCC). A phytochemical screening demonstrated the presence of eight constituents, being geranial the major compound (43.08 percent). In rats, EOCC (1, 5, 10, and 20 mg/kg, i.v.) induced transient hypotension and bradycardia that were attenuated by atropine and sodium thiopental, but not by L-NAME or indomethacin. In rings of rat superior mesenteric artery pre-contracted with phenylephrine, EOCC (1 to 3000 µg/mL) induced relaxation that was not affected after removal of the endothelium, after TEA or in rings pre-contracted with KCl (80 mM). Furthermore, EOCC (1000 µg/mL) was not able to induce additional effect on maximal relaxation of nifedipine (10 µM). In conclusions, EOCC induces hypotension, possibly by reduction in vascular resistance caused by inhibition of the Ca2+ influx, and bradycardia probably due to an activation of cardiac muscarinic receptors.

C. citratus é utilizada na medicina popular para tratar hipertensão. Este trabalho investigou a composição química e os efeitos cardiovasculares do óleo essencial do C. citratus (OECC). Foram identificados oito constituintes no OECC, sendo geranial o majoritário (43,08 por cento). Em ratos, o OECC (1, 5, 10 e 20 mg/kg, i.v.) induziu hipotensão e bradicardia que foram atenuadas pela atropina e tiopental sódico, mas não por L-NAME ou indometacina. Em anéis de artéria mesentérica de ratos pré-contraídos com fenilefrina, o OECC (1 a 3000 µg/mL) induziu relaxamento que não foi afetado após remoção do endotélio, após TEA ou em anéis pré-contraídos com KCl (80 mM). Além disso, o OECC (1000 µg/mL) não induziu efeito adicional sobre o relaxamento máximo da nifedipina (10 µM). Em conclusão, o OECC induz hipotensão possivelmente devido à redução da resistência vascular que pode ser causada por inibição do influxo de Ca2+, e bradicardia provavelmente devido à ativação de receptores muscarínicos cardíacos.

Antinociceptive and anti-inflammatory effects of Costus spicatus in experimental animals.

CONTEXT: Costus spicatus Swartz (Costaceae), commonly called "cana-do-brejo'" in Brazil's northeast, is a medicinal plant found in wet coastal forests. In folk medicine an infusion of the aerial parts is taken to treat inflammation and pain. OBJECTIVE: The methanol extract obtained from the leaves of Costus spicatus (MECs) was evaluated for antinociceptive and anti-inflammatory activities. METHODS: Analgesic and anti-inflammatory activities were studied by measuring nociception through acetic acid, formalin, and hot-plate tests, while inflammation was induced by carrageenan. All experiments were conducted with experimental animals. RESULTS AND DISCUSSION: Following oral administration, MECs (100, 200, and 400 mg/kg) significantly reduced the number of writhes (52.8, 43.1, and 55.3%, respectively) in the writhing test and the number of paw licks during phase 1 (61.9, 54.1, and 92.1%) and phase 2 (62.5, 82.9, and 98.1%, all doses) during the formalin test when compared to the control group animals. The reaction time during the hot-plate test was increased significantly and was dose-dependent, whereas pretreatment with naloxone rigorously reduced the analgesic potential of MECs, which suggested participation of the opioid system in the modulation of pain induced by MECs. Such results were unlikely to be provoked by motor abnormality, as MECs-treated mice did not exhibit any performance alteration during the Rota-rod test. The administration of 200 and 400 mg/ kg (i.p.) of MECs exhibited an anti-inflammatory effect during the carrageenan test, which was based on interference with inflammatory mediator synthesis. CONCLUSION: We conclude that MECs has antinociceptive and anti-inflammatory activities in rodents.

Hypotensive and vasorelaxant effects of citronellol, a monoterpene alcohol, in rats.

Citronellol is an essential oil constituent from the medicinal plants Cymbopogon citratus, Cymbopogon winterianus and Lippia alba which are thought to possess antihypertensive properties. Citronellol-induced cardiovascular effects were evaluated in this study. In rats, citronellol (1-20 mg/kg, i.v.) induced hypotension, which was not affected by pre-treatment with atropine, hexamethonium, N(omega)-nitro-L-arginine methyl ester hydrochloride or indomethacin, and tachycardia, which was only attenuated by pre-treatment with atropine and hexamethonium. These responses were less than those obtained for nifedipine, a reference drug. In intact rings of rat mesenteric artery pre-contracted with 10 microM phenylephrine, citronellol induced relaxations (pD(2) = 0.71 +/- 0.11; E(max) = 102 +/- 5%; n = 6) that were not affected by endothelium removal, after tetraethylamonium in rings without endothelium pre-contracted with KCl 80 mM. Citronellol strongly antagonized (maximal inhibition = 97 +/- 4%; n = 6) the contractions induced by CaCl(2) (10(-6) to 3 x 10(-3 )M) and did not induce additional effects on the maximal response of nifedipine (10 microM). Finally, citronellol inhibited the contractions induced by 10 microM phenylephrine or 20 mM caffeine. The present results suggest that citronellol lowers blood pressure by a direct effect on the vascular smooth muscle leading to vasodilation.

Relaxant effect of the aqueous extract of Erythrina vellutina leaves on rat vas deferens

The effect of the Aqueous Extract from the leaves of Erythrina vellutina (AE) on rat vas deferens preparation was evaluated in this work. The AE inhibited the muscle contractions induced by electrical field stimulation (EFS) in a concentration-dependent manner. This inhibition was not affected by atropine (10-5M), propanolol (10-5M), prazosin (10-5M) or yohimbine (10-5M), suggesting that there is no direct interaction of the AE with cholinergic nor adrenergic receptors. Incubation of vas deferens with the K+ channel antagonists, tetraethylamonium (10-6M) or 4-aminopyridine (10-6M) had also no effect on the AE-induced inhibition. On the other hand, glibenclamide (10-6) significantly attenuated the effect of the AE, suggesting a possible involvement of ATP-dependent K+ channels. The AE (0.15 mg/mL) did not alter the contractions induced by noradrenaline (10-5M), ATP (10-4M) nor KCl (80 mM), against an interaction of the extract with post-synaptic sites. The data presented suggests that the inhibition of the electrically driven muscle twitches by the AE could be due to a pre-synaptic interaction of the extract with ATP-dependent K+ channels from vas deferens sympathetic neurons.

O objetivo deste trabalho foi avaliar o efeito do extrato aquoso das folhas de Erythrina vellutina (AE) sobre ducto deferente de rato. Nesta preparação, o AE inibiu as contrações induzidas por estímulo elétrico de campo de maneira dependente da concentração. Esta inibição não foi afetada após atropina (10-5M), propanolol (10-5M), prazosin (10-5M) ou yohimbina (10-5M), sugerindo uma ação indireta do AE sobre receptores colinérgicos ou adrenérgicos. A incubação da preparação com os antagonistas de canais de K+, tetraetilâmonio (10-6M) ou 4-aminopiridina (10-6M) não alterou o efeito inibitório induzido pelo AE. Entretanto, a glibenclamida (10-6M) atenuou significantemente este efeito, sugerindo um possível envolvimento de canais de K+ dependentes de ATP. Além disso, o AE (0.15 mg/mL) não alterou as contrações induzidas por noradrenalina (10-5M), ATP (10-4M) ou KCl (80 mM), descartando uma interação do AE com um sítio pós-sináptico. Em conclusão, estes resultados demonstram que o efeito inibitório do AE pode ser devido a uma interação pré-sináptica com canais de K+ dependentes de ATP em neurônios simpáticos de ducto deferente de rato.

Cardiovascular effects of the aqueous extract from Caesalpinia ferrea: involvement of ATP-sensitive potassium channels.

Caesalpinia ferrea is a plant very used in the folk medicine for treatment of several diseases, such as diabetes. This study investigated the cardiovascular effects of the aqueous extract from stem bark of C. ferrea (AECF). In non-anesthetized rats, AECF (10, 20, 40, 60 and 80 mg/kg; i.v.) induced hypotension (-9+/-1;-12+/-1;-14+/-1; -20+/-3 and -51+/-6%; respectively) and tachycardia (6+/-1; 8+/-1; 12+/-2; 14+/-2 and 26+/-3%; respectively). Hypotension was not affected after atropine or L-NAME. Furthermore, AECF (40 mg/kg) induced atrioventricular block and extrasystoles, which was not affected after atropine. In intact rings of the rat mesenteric artery, AECF (0.001-30 mg/ml, n=6) induced relaxations of phenylephrine tonus (Emax=110+/-4%), which was not changed after the removal of endothelium (Emax=113+/-9%). In rings without endothelium pre-contracted with KCl 80 mM, phenylephrine plus KCl 20 mM or phenylephrine plus glibenclamide, the curve to AECF was significantly attenuated (Emax=24+/-4%, 70+/-5% and 62+/-7%, respectively, n=6), but was not affected in the presence of tetraethylammonium or 4-aminopyridine (Emax=125+/-15% and 114+/-7%, respectively, n=6). These results demonstrate that AECF induces hypotension associated to tachycardia; however, in dose of 40 mg/kg, AECF induces transient bradyarrhythmias. Furthermore, AECF induces vasodilatation in rat mesenteric artery which appears to be mediated by ATP-sensitive K+ channel openings.