Most of the hematophagous insects act as disease vectors, including Aedes aegypti, responsible for transmitting some of the most critical arboviruses globally, such as Dengue. The use of repellents ...based on natural products is a promising alternative for personal protection compared to industrial chemical repellents. In this study, the repellent effect of essential oils extracted from Lippia thymoides, Lippia alba, Cymbopogon winterianus, and Eucalyptus globulus leaves was evaluated. Essential oils used showed repellent activity against Ae. aegypti in laboratory bioassays, obtaining protection rates above 70 % from 3.75 mg/mL and higher concentration for all analyzed oils. GC/MS identified 57 constituents, which were used in the ligand‐based pharmacophore model to expose compounds with requirements for repellents that modulate mosquitoes behavior through odorant‐binding protein 1 Ae. aegypti. Ligand‐based pharmacophore model approach results suggested that repellent activity from C. winterianus, L. alba, and L. thymoides essential oils’ metabolites is related to Citronelal (QFIT=26.77), Citronelol (QFIT=11.29), Citronelol acetate (QFIT=52.22) and Geranil acetate (QFIT=10.28) with synergistic or individual activity. E. globulus essential oil's repellent activity is associated with Ledol (0.94 %; QFIT=41.95). Molecular docking was applied to understand the binding mode and affinity of the essential oils’ data set at the protein binding site. According to molecular docking, Citronelol (ChemPLP=60.98) and geranyl acetate (ChemPLP=60.55) were the best‐classified compounds compared to the others and they can be explored to develop new repellents.
The traditional use of the M. charantia L. plant to treat coughs, fever and expectoration is widely practiced in different cultures, but its effectiveness and safety still require scientific ...investigation. This study sought to perform a chemical analysis and evaluate the antitussive, expectorant and antipyretic effects of the ethanolic extract of M. charantia leaves (EEMc) in rats and mice. The EEMc was subjected to chemical analysis by HPLC‐DAD, revealing the presence of the flavonoids astragalin and isoquercetin. Acute oral toxicity in mice did not result in deaths, although changes in liver weight and stool consistency were observed. EEMc demonstrated an antitussive effect at doses of 100 and 300 mg/kg in mice subjected to cough induction by citric acid nebulization. Furthermore, it showed expectorant activity at a dose of 300 mg/kg, assessed based on the elimination of the phenol red marker in bronchoalveolar lavage. In the evaluation of antipyretic activity in rats, fever induced by Saccharomyces cerevisiae was reduced at all doses tested during the first hour after treatment. This innovative study identified the presence of astragalin and isoquercetin in EEMc and indicated that the extract has antitussive, expectorant and antipyretic properties. Therefore, EEMc presents itself as a promising option in herbal medicine for the treatment of respiratory symptoms and fever.
Although the root of Cannabis sativa L. has been mentioned in some regions, such as the Vale do São Francisco, for its potential traditional medicinal use as an anti-inflammatory, anti-asthmatic, and ...against gastrointestinal diseases, it has received little exploration and discussion.
This study aimed to perform a chemical analysis of an aqueous extract of Cannabis sativa roots (AqECsR) and evaluate its pharmacological effects against uterine disorders, in vivo and ex vivo, in rodents.
The roots were provided by the Brazilian Federal Police, and the freeze-dried extract was used for the chemical analysis of the AqECsR by high performance liquid chromatography coupled with mass spectrometry (HPLC-MS). The sample was subsequently used in three doses for pharmacological assays (12.5, 25, and 50 mg/kg), which included the spasmolytic activity test and the primary dysmenorrhea test. The primary dysmenorrhea test aimed to verify the effect of AqECsR on induced abdominal contortions in female mice in vivo and to perform a morphometric analysis of the organs. Association tests at subtherapeutic doses of AqECsR with antidysmenorrheic drugs were also performed.
The data obtained by HPLC-MS suggested the presence of four substances: cannabisativine, anhydrocannabisativine, feruloyltyramine, and p-coumaroyltyramine. In the pharmacological assays, the AqECsR showed no spasmolytic effect. However, in the antidysmenorrheal activity test, AqECsR demonstrated a significant in vivo effect of reducing oxytocin-induced abdominal contortions. Morphometric analysis of the uterus showed no significant organ enlargement effect, and the association of AqECsR with subtherapeutic doses of three drugs used in antidysmenorrheal therapy (mefenamic acid, scopolamine, and nifedipine) showed an effect in reducing abdominal contortions.
In conclusion, AqECsR contains four chemical compounds and exhibits an antidysmenorrheic effect both alone and in association with drugs, reducing abdominal contortions in female mice without generating organ enlargement in the animals. Further studies are needed to prove the mechanism of action by which AqECsR promotes its effect on primary dysmenorrhea and to explore its associations.
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•Cannabisativine, anhydrocannabisativine, p-coumaroyltyramine and feruloyltyramine were identified in AqECsR.•AqECsR reduce abdominal contortions in a mouse model of primary dysmenorrhea.•Subtherapeutic doses of AqECsR associated with three antidysmenorrheal drugs showed a reduction in abdominal contortions.•Morphometric analysis of the uterus showed no significant organ enlargement effect.•AqECsR did not show spasmolytic activities.
Diabetes mellitus (DM) is a chronic disease characterised by high levels of glucose in the blood, resulting from a relative or absolute deficiency in the action of insulin. It is now clear that a ...state of chronic low- level inflammation is closely associated with the pathophysiology of DM, which may contribute to the long-term effects of the disease. Some monoterpenes, compounds present in oils from various aromatic plants, such as β- pinene, have antidiabetic and anti-inflammatory properties. Thus, the current study sought to assess the hypoglycemic, hypolipidemic, and anti-inflammatory effects of α-pinene, an isomer of β-pinene, in diabetic rats. Methods: Male Wistar rats (200–250 g) received a single injection of alloxan (40 mg/kg) through the penile vein to induce diabetes. Diabetic animals were orally treated with vehicle or α-pinene (25, 50, 100 mg/kg) or glibenclamide (5 mg/kg) for seven consecutive days. On the last day of treatment, blood samples were collected for biochemical analysis and the anti-inflammatory effect of α-pinene was evaluated using the carrageenan-induced paw edema and carrageenan-induced peritonitis models. Results: The treatment with the monoterpene decreased blood glucose, cholesterol, triglyceride, VLDL, LDL, HDL, AST and ALT levels when compared to the vehicle group. Likewise, the association α-pinene + glibenclamide also decreased blood glucose, total cholesterol and triglyceride levels. The oral treatment with α-pinene inhibited carrageenan-induced recruitment of total leukocytes to the peritoneal cavity and also inhibited carrageenan-induced paw edema. Alpha-pinene showed significant hypoglycemic and hypolipemic activity at doses 25, 50 and 100 mg/kg. The strongest anti-inflammatory activity of α-pinene was observed at a dose of 50 mg/kg. Finally, these findings suggest that α-pinene may have anti-inflammatory, hypoglycemic, and hypolipemic properties. Its anti-inflammatory properties are probably an asset for the treatment of diabetes and its complications. However, new preclinical tests are required to elucidate the mechanism of action by which α-pinene exerts its activity.
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•The α-pinene showed a hypoglycemic effect in alloxan-induced diabetic animals.•The possible mechanism is the inhibition of ATP-sensitive K+ channels (KATP), as glibenclamide.•The α-pinene reduced both cholesterol and triglyceride fractions.•The association of α-pinene + Glib caused a short-term reduction in blood glucose.•The α-pinene showed an important anti-inflammatory effect.
The species Lippia origanoides Kunth, popularly known as “salva-de-marajó”, is used in Brazilian traditional “quilombola” communities to treat menstrual cramps and uterine inflammation.
Evaluate the ...spasmolytic activity of Lippia origanoides essential oil (LOO) on experimental models of uterine conditions related to menstrual cramps and investigate its mechanism of action.
Virgin rat-isolated uterus was mounted in the organ bath apparatus to evaluate the spasmolytic effect of LOO on basal tonus and contractions induced by carbachol, KCl, or oxytocin. We used pharmacological agents to verify the relaxation mechanism of LOO. The evaluation of uterine contractility in virgin rats, after treatment with LOO for three consecutive days, was carried out by the construction of a concentration-response curve with oxytocin or carbachol. The primary dysmenorrhea animal model was replicated with an injection of estradiol cypionate in female mice for three consecutive days, followed by intraperitoneal application of oxytocin.
LOO relaxed the rat uterus precontracted with 10−2 IU/mL oxytocin (logEC50 = 1.98 ± 0.07), 1 μM carbachol (logEC50 = 1.42 ± 0.07) or 60 mM KCl (logEC50 = 1.53 ± 0.05). It was also able relax uterus on spontaneous contractions (logEC50 = 0.41 ± 0.05). Preincubation with glibenclamide, propranolol, phentolamine or L-NAME in contractions induced by carbachol did not alter significantly the relaxing effect of LOO. However, in the presence of 4-aminopyridine, CsCl or tetraethylammonium there was a reduction of LOO potency, whereas the blockers methylene blue, ODQ, aminophylline and heparin potentiated the LOO relaxing effect. Preincubation with LOO in a Ca2+ free medium at concentrations of 27 μg/mL or 81 μg/mL reduced the contraction induced by carbachol. The administration of LOO for 3 days did not alter uterus contractility. The treatment with LOO at 30 or 100 mg/kg intraperitoneally, or 100 mg/kg orally, inhibited writhing in female mice. The association of LOO at 10 mg/kg with nifedipine or mefenamic acid potentiated writhing inhibition in mice.
The essential oil of L. origanoides has tocolytic activity in rat isolated uterus pre-contracted with KCl, oxytocin, or carbachol. This effect is possibly related to the opening of potassium channels (Kir, KV, and KCa), cAMP increase, and diminution of intracellular Ca2+. This relaxant effect, probably, contributed to reduce the number of writhings in an animal model of dysmenorrhea being potentiated by nifedipine or mefenamic acid. Taken together, the results here presented indicate that this species has a pharmacological potential for the treatment of primary dysmenorrhea, supporting its use in folk medicine.
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•Lippia origanoides essential oil (LOO) has spasmolytic effect in isolated rat uterus.•The spasmolytic effect of LOO was dependent on the K+ channels, cAMP increasing, and reduction of Ca2+i.•Lippia origanoides essential oil presented anti-dysmenorrhea activity in mice.•Nifedipine and mefenamic acid potentiated the anti-dysmenorrhea activity of LOO.
Pain and inflammation are unpleasant experiences that usually occur as a result of tissue damage. Despite the number of existing analgesic drugs, side effects limit their use, stimulating the search ...for new therapeutic agents. In this sense, five hydrazone derivatives (H1, H2, H3, H4, and H5), with general structure R1R2C = NNR3R4, were synthesized with molecular modification strategies. In this paper, we describe the ability of hydrazone derivatives to attenuate nociceptive behavior and the inflammatory response in mice. Antinociceptive activity was evaluated through acetic acid-induced writhing and formalin-induced nociception tests. In both experimental models, the hydrazone with the greatest potency (H5) significantly (p < 0.05) reduced nociceptive behavior. Additionally, methods of acute and chronic inflammation induced by different chemicals (carrageenan and histamine) were performed to evaluate the anti-inflammatory effect of H5. Moreover, molecular docking analysis revealed that H5 can block the COX-2 enzyme, reducing arachidonic acid metabolism and consequently decreasing the production of prostaglandins, which are important inflammatory mediators. H5 also changes locomotor activity. In summary, H5 exhibited relevant antinociceptive and anti-inflammatory potential and acted on several targets, making it a candidate for a new multi-target oral anti-inflammatory drug.
Carvacrol is a phenolic constituent of essential oils that has antinociceptive, anti-inflammatory, and antioxidant activities.
This study aimed to evaluate the in vitro spasmolytic and in vivo ...anti-dysmenorrhea potential of a nanoemulsion-containing carvacrol (nanoCARV).
In isolated rat uterus, nanoCARV reduced spontaneous contractions (pEC50 = 3.91 ± 0.25) and relaxed preparations pre-contracted with oxytocin (pEC50 = 3.78 ± 0.2), carbachol (pEC50 = 4.15 ± 0.4), prostaglandin F2α (pEC50 = 3.00 ± 0.36), and KCl (pEC50 = 3.98 ± 0.32). The investigation of the mechanism of action revealed significant differences (p < 0.05) between the pEC50 values of nanoCARV in the absence or presence of aminophylline or tetraethylammonium. In a primary dysmenorrhea model, treatment with nanoCARV reduced the number of oxytocin-induced abdominal writhes.
These data indicate that the anti-dysmenorrhea effect of nanoCARV may be related to the relaxation of uterine smooth muscle, with participation of the cAMP signaling pathway and potassium channels.
Abstract The traditional use of the M. charantia L. plant to treat coughs, fever and expectoration is widely practiced in different cultures, but its effectiveness and safety still require scientific ...investigation. This study sought to perform a chemical analysis and evaluate the antitussive, expectorant and antipyretic effects of the ethanolic extract of M. charantia leaves (EEMc) in rats and mice. The EEMc was subjected to chemical analysis by HPLC‐DAD, revealing the presence of the flavonoids astragalin and isoquercetin. Acute oral toxicity in mice did not result in deaths, although changes in liver weight and stool consistency were observed. EEMc demonstrated an antitussive effect at doses of 100 and 300 mg/kg in mice subjected to cough induction by citric acid nebulization. Furthermore, it showed expectorant activity at a dose of 300 mg/kg, assessed based on the elimination of the phenol red marker in bronchoalveolar lavage. In the evaluation of antipyretic activity in rats, fever induced by Saccharomyces cerevisiae was reduced at all doses tested during the first hour after treatment. This innovative study identified the presence of astragalin and isoquercetin in EEMc and indicated that the extract has antitussive, expectorant and antipyretic properties. Therefore, EEMc presents itself as a promising option in herbal medicine for the treatment of respiratory symptoms and fever.
Chikungunya fever has become a relevant public health problem in countries where epidemics occur. Until 2013, only imported cases occurred in the Americas, but in October of that year, the first ...cases were reported in Saint Marin island in the Caribbean. The first autochthonous cases were confirmed in Brazil in September 2014; until epidemiological week 37 of 2016, 236,287 probable cases of infection with Chikungunya virus had been registered, 116,523 of which had serological confirmation. Environmental changes caused by humans, disorderly urban growth and an ever-increasing number of international travelers were described as the factors responsible for the emergence of large-scale epidemics. Clinically characterized by fever and joint pain in the acute stage, approximately half of patients progress to the chronic stage (beyond 3 months), which is accompanied by persistent and disabling pain. The aim of the present study was to formulate recommendations for the diagnosis and treatment of Chikungunya fever in Brazil. A literature review was performed in the MEDLINE, SciELO and PubMed databases to ground the decisions for recommendations. The degree of concordance among experts was established through the Delphi method, involving 2 in-person meetings and several online voting rounds. In total, 25 recommendations were formulated and divided into 3 thematic groups: (1) clinical, laboratory and imaging diagnosis; (2) special situations; and (3) treatment. The first 2 themes are presented in part 1, and treatment is presented in part 2.
A febre chikungunya tem se tornado um importante problema de saúde pública nos países onde ocorrem as epidemias. Até 2013, as Américas haviam registrado apenas casos importados quando, em outubro desse mesmo ano, foram notificados os primeiros casos na Ilha de Saint Martin, no Caribe. No Brasil, os primeiros relatos autóctones foram confirmados em setembro de 2014 e até a semana epidemiológica 37 de 2016 já haviam sido registrados 236.287 casos prováveis de infecção pelo chikungunya vírus (CHIKV), 116.523 confirmados sorologicamente. As mudanças ambientais causadas pelo homem, o crescimento urbano desordenado e o número cada vez maior de viagens internacionais têm sido apontados como os fatores responsáveis pela reemergência de epidemias em grande escala. Caracterizada clinicamente por febre e dor articular na fase aguda, em cerca de metade dos casos existe evolução para a fase crônica (além de três meses), com dor persistente e incapacitante. O objetivo deste trabalho foi elaborar recomendações para diagnóstico e tratamento da febre chikungunya no Brasil. Para isso, foi feita revisão da literatura nas bases de dados Medline, SciELO e PubMed, para dar apoio às decisões tomadas para definir as recomendações. Para a definição do grau de concordância foi feita uma metodologia Delphi, em duas reuniões presenciais e várias rodadas de votação on line. Foram geradas 25 recomendações, divididas em três grupos temáticos: (1) diagnóstico clínico, laboratorial e por imagem; (2) situações especiais e (3) tratamento. Na primeira parte estão os dois primeiros temas e o tratamento na segunda.
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