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1.
Toxicol Appl Pharmacol ; 484: 116873, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38417591

RESUMO

This study analyzed how glyphosate exposure in the gestational period affects vascular function in their female offspring and whether oxidative stress is involved in this effect. To this, pregnant Wistar rats were exposed through drinking water to 0.2% of a glyphosate commercial formulation, and we analyzed the response to acetylcholine and phenylephrine in the aorta from offspring of Glyphosate-based herbicide (O-GBH) and controls (O-CON) rats at six months of age. Relaxation to acetylcholine was reduced in O-GBH than in O-CON. Acute Indomethacin and Apocynin increased relaxation to acetylcholine in O-GBH. The aorta from O-GBH was hyperactive to phenylephrine; the preincubation with N-nitro-L-arginine methyl ester (L-NAME) increased contraction to phenylephrine more in O-CON than O-GBH. TEMPOL similarly reduced phenylephrine response, and L-NAME prevented this effect. The TBARS and GSH levels were increased in O-GBH than in O-CON. Results reinforce the concept that oxidative stress during the perinatal period contributes to the development of vascular changes in adulthood. Results also reveal that oxidative stress parameters altered, and the current levels considered safe for exposure to Glyphosate deserve further investigation, especially in the female gender.


Assuntos
60658 , Herbicidas , Gravidez , Humanos , Ratos , Animais , Feminino , Herbicidas/toxicidade , Ratos Wistar , NG-Nitroarginina Metil Éster , Exposição Materna/efeitos adversos , Acetilcolina , Glicina/toxicidade , Fenilefrina/toxicidade
2.
Reprod Toxicol ; 115: 94-101, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36543306

RESUMO

This study analyzed how glyphosate exposure in the gestational period affects vascular function in their offspring, focusing on the influence of age and whether oxidative stress is involved in this effect. To this, pregnant Wistar rats were exposed through drinking water to 0.2% of a glyphosate commercial formulation, and we analyzed the response to acetylcholine and phenylephrine in the aorta from offspring of glyphosate herbicide-based (O-GHB) and controls (O-CON) rats at 3, 6, and 12 months of age. O-GHB groups showed no changes in arterial blood pressure or aorta histological analysis. Relaxation to acetylcholine was reduced in O-GHB than O-CON. Acute TEMPOL increased relaxation to acetylcholine in O-GHB at 6 and 12 months of age. The aorta from O-GHB was hyperactive to phenylephrine only at 6 months of age. Preincubation with N-nitro-L-arginine methyl ester (L-NAME) increased contraction to phenylephrine more in O-CON than O-GHB. TEMPOL similarly reduced phenylephrine response. This effect was prevented by L-NAME. Results reinforce the concept that oxidative stress during the perinatal period contributes to the development of vascular changes in adulthood. Results also reveal that although no changes in cardiac or histological parameters have been demonstrated, the current levels considered safe for exposure to glyphosate deserve further investigation, especially during pregnancy.


Assuntos
Herbicidas , Hipertensão , Oxibato de Sódio , Gravidez , Humanos , Feminino , Ratos , Animais , NG-Nitroarginina Metil Éster/farmacologia , Ratos Wistar , Acetilcolina/farmacologia , Herbicidas/toxicidade , Exposição Materna/efeitos adversos , Oxibato de Sódio/farmacologia , Fenilefrina/toxicidade , Endotélio Vascular , Pressão Sanguínea
3.
J Psychopharmacol ; 36(7): 836-848, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35723216

RESUMO

BACKGROUND: Depression is a psychiatric disorder with limited therapy options. Psychedelics are new antidepressant candidates, being the ayahuasca one of the most promising ones. A synergistic combination of N,N-dimethyltryptamine (DMT) and ß-carbolines allows ayahuasca antidepressant properties. Another psychedelic and DMT-containing beverage is the jurema wine used religiously by indigenous people from Northeastern Brazil. AIMS: To evaluate the antidepressant-like effect of standardized extract of Mimosa tenuiflora (SEMT), associated or not with harmine (ß-carboline), in behavioral models of depression. METHODS: The SEMT was submitted to (+) ESI-IT-LC/MS analysis for DMT quantification. To assess the antidepressant-like effect of SEMT, the open field (OFT), tail suspension (TST), and forced swim (FST) tests were performed. To verify the participation of serotonergic systems, the 5-hydroxytryptophan (5-HTP)-induced head twitch test was performed. RESULTS: The content of DMT found in SEMT was 24.74 ± 0.8 mg/g. Yuremamine was also identified. SEMT presented an antidepressant-like effect in mice submitted to the TST and FST, independent from harmine, with no significant alterations on the OFT. The sub-dose interaction between SEMT and ketamine also produced an anti-immobility effect in the TST, with no changes in the OFT. SEMT potentiated the head twitch behavior induced by 5-HTP and ketanserin prevented its antidepressant-like effect in the TST (p < 0.05). CONCLUSIONS: SEMT presented a harmine-independent antidepressant-like effect in mice submitted to the TST and FST. This effect occurs possibly via activation of serotonergic systems, particularly the 5-HT2A/2C receptors.


Assuntos
Mimosa , Serotonina , 5-Hidroxitriptofano/farmacologia , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Carbolinas , Depressão/tratamento farmacológico , Depressão/psicologia , Harmina , Humanos , Camundongos , Natação
4.
J Ethnopharmacol ; 290: 115099, 2022 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-35167934

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: 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. AIM OF THE STUDY: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.


Assuntos
Dismenorreia/patologia , Lippia , Óleos Voláteis/farmacologia , Tocolíticos/farmacologia , Útero/efeitos dos fármacos , Animais , Cálcio/metabolismo , Carbacol/farmacologia , AMP Cíclico/metabolismo , Feminino , Ácido Mefenâmico/farmacologia , Contração Muscular/efeitos dos fármacos , Nifedipino/farmacologia , Ocitocina/farmacologia , Canais de Potássio/efeitos dos fármacos , Cloreto de Potássio/farmacologia , Ratos , Contração Uterina/efeitos dos fármacos
5.
Planta Med ; 88(13): 1223-1232, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34715694

RESUMO

Cannabis sativa is a millenary medicinal plant. However, contrary to worldwide paradigm-shifting, countries like Brazil still prohibit C. sativa cultivation and its medicinal use, even though many populations use aerial parts and roots of this plant for healthcare. As such, the objective of this work was to identify substances in the samples of the C. sativa roots, tracing a correlation with antitussive and expectorant effects. Therefore, samples of C. sativa roots were donated by the Polícia Federal Brasileira, and its aqueous extract (AECsR) was prepared with subsequent lyophilization, to maintain the material stability. After that, the material was analyzed by LC-MS to observe its chemical profile. Four samples (AECsR-A, B, C, and D) were tested in animal models of citric acid-induced cough (0.4 M) and phenol red expectoration (500 mg/kg). Using LC-MS it was possible to identify 5 molecules in C. sativa roots: p-coumaroyltyramine, tetrahydrocannabinol-C4, feruoiltyramine, anhydrocanabisativine, and cannabisativine. In experimental protocols, male mice (Mus musculus) were treated with samples of AECsR at doses of 12.5, 25, or 50 mg/kg regardless of the pharmacological test. In these tests, all samples showed the potential to treat cough and promote fluid expectoration, differing only in the dose at which these effects were observed. Therefore, the data showed that the C. sativa roots of the Brazilian Northeast showed antitussive and expectorant effects, even with intense secondary metabolites' variation, which alters its potency, but not its effect. This highlights the importance of this medicinal plant for future therapy and corroborates to traditional use.


Assuntos
Antitussígenos , Cannabis , Plantas Medicinais , Camundongos , Animais , Antitussígenos/farmacologia , Antitussígenos/uso terapêutico , Expectorantes/farmacologia , Expectorantes/uso terapêutico , Tosse/induzido quimicamente , Tosse/tratamento farmacológico , Brasil , Fenolsulfonaftaleína , Cromatografia Líquida , Dronabinol/uso terapêutico , Espectrometria de Massas em Tandem , Plantas Medicinais/química , Ácido Cítrico/toxicidade , Ácido Cítrico/uso terapêutico
6.
J Ethnopharmacol ; 278: 114259, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34058314

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Many studies are performed with the aerial parts of Cannabis sativa L. (Cannabaceae). However, roots remain poorly studied, despite citations in the scientific literature. The C. sativa roots are indicated for the treatment of pain, inflammation, fever, among other health problems. AIM OF THE STUDY: This study aimed to evaluate the antinociceptive, antipyretic, antiasthmatic, and spasmolytic activities of C. sativa roots in experimental models using mice and rats. MATERIAL AND METHODS: The chemical composition of the aqueous extract of C. sativa roots (AECsR) was evaluated by LC-MS. The antinociceptive activity was assessed in mice by the induction of writhing with acetic acid, paw licking with formalin, and reactivity in the hot plate test. Fever was induced by the administration of a suspension of Saccharomyces cerevisiae in young rats. The asthmatic activity was performed with ovalbumin (OVA)-immunized mice with cellular and histological analysis. Finally, the spasmolytic activity was performed using mice isolated trachea. For in vivo studies, the doses were 12.5, 25, or 50 mg/kg whereas for in vitro, the concentration of AECsR was 729 µg/mL. RESULTS: From the LC-MS data, we identified p-coumaroyltyramine, feruloyltyramine canabissativine in AECsR. The extract promoted a reduction of writhing in all tested doses (12.5, 25, or 50 mg/kg). Similarly, it reduced the pain in the formalin test at doses of 12.5 and 50 mg/kg (first phase) and 12.5 and 25 mg/kg (second phase). In the hot plate test, the doses of 12.5, 25, and 50 mg/kg promoted antinociceptive effect at different times, and the lowest dose maintained its action in the analyzes performed at 60, 90, and 120 min after administration. The anti-inflammatory activity of AECsR was observed in the mouse model of asthma, reducing the total leukocyte count in the bronchoalveolar fluid (BALF) at a dose of 25 mg/kg, as well as reducing eosinophilia in all tested doses (12.5, 25, and 50 mg/kg). Histological analysis of lungs stained with H&E and PAS showed a reduction in the number of inflammatory cells in the perivascular and peribronchial region, as well as reduced mucus production. CONCLUSION: The results suggest that AECsR promotes pain control, either by a central or inflammatory mechanism, and has antiasthmatic activity. However, there was no antipyretic or spasmolytic effect.


Assuntos
Analgésicos/farmacologia , Antiasmáticos/farmacologia , Cannabis/química , Extratos Vegetais/farmacologia , Analgésicos/administração & dosagem , Analgésicos/isolamento & purificação , Animais , Antiasmáticos/administração & dosagem , Antiasmáticos/isolamento & purificação , Antipiréticos/administração & dosagem , Antipiréticos/isolamento & purificação , Antipiréticos/farmacologia , Brasil , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Febre/tratamento farmacológico , Inflamação/tratamento farmacológico , Masculino , Camundongos , Dor/tratamento farmacológico , Parassimpatolíticos/administração & dosagem , Parassimpatolíticos/isolamento & purificação , Parassimpatolíticos/farmacologia , Extratos Vegetais/administração & dosagem , Raízes de Plantas , Ratos , Ratos Wistar
8.
J Ethnopharmacol ; 271: 113868, 2021 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-33503453

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: There are many studies and therapeutic properties attributed to the flowers and leaves of the Cannabis species, but even with few pharmacological studies, Cannabis sativa L. (Cannabaceae) roots presents several therapeutic indications in folk medicine. AIM OF THE STUDY: This study aimed to evaluate the anti-inflammatory and spasmolytic effects as well as the toxicological profile of the aqueous extract of Cannabis sativa roots (CsAqEx) in mice. MATERIALS AND METHODS: We assessed the anti-inflammatory effect with carrageenan-induced leukocyte migration assay, and carrageenan and histamine-induced paw edema methods; The spasmolytic effect was assessed through in vitro assays with isolated mice trachea. To assess motor coordination and mobility, mice went through the rotarod and open field tests, respectively. For the single-dose toxicity study, we administered CsAqEx at the dose of 1000 mg/kg by gavage. In a repeated dose toxicity study, animals received CsAqEx at doses of 25 mg or 100 mg/kg for 28 days. RESULTS: The CsAqEx inhibited the migration of leukocytes at the doses of 25, 50, and 100 mg/kg. The CsAqEx showed anti-inflammatory activity after the intraplantar injection of carrageenan, presenting a reduction in edema formation at all tested doses (12.5, 25, 50 and 100 mg/kg). The dose of 12.5 mg/kg of CsAqEx prevented edema formation after intraplantar injection of histamine. In an organ bath, 729 µg/mL of CsAqEx did not promote spasmolytic effect on isolated mice tracheal rings contracted by carbachol (CCh) or potassium chloride (KCl). We did not observe clinical signs of toxicity in the animals after acute treatment with CsAqEx, which suggested that the median lethal dose (LD50) is greater than 1000 mg/kg. Repeated dose exposure to the CsAqEx did not produce significant changes in hematological, biochemical, or organ histology parameters. CONCLUSIONS: The results suggest that the anti-inflammatory effect of CsAqEx is related to the reduction of vascular extravasation and migration of inflammatory cells, without effects on the central nervous system. Moreover, there was no spasmolytic effect on airway smooth muscle and no toxicity was observed on mice.


Assuntos
Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/toxicidade , Cannabis/química , Parassimpatolíticos/farmacologia , Parassimpatolíticos/toxicidade , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidade , Administração Oral , Animais , Anti-Inflamatórios/administração & dosagem , Comportamento Animal/efeitos dos fármacos , Carragenina/toxicidade , Edema/induzido quimicamente , Edema/prevenção & controle , Histamina/toxicidade , Inflamação/induzido quimicamente , Inflamação/prevenção & controle , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Camundongos , Músculo Liso/efeitos dos fármacos , Teste de Campo Aberto/efeitos dos fármacos , Parassimpatolíticos/administração & dosagem , Extratos Vegetais/administração & dosagem , Raízes de Plantas/química , Desempenho Psicomotor/efeitos dos fármacos , Teste de Desempenho do Rota-Rod , Estômago/efeitos dos fármacos , Estômago/patologia , Traqueia/efeitos dos fármacos
9.
Nat Prod Res ; 35(24): 6200-6203, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33121280

RESUMO

Jatropha mutabilis (Pohl) Baill is an endemic species of the Caatinga biome, little studied in terms of chemical composition. The objective of this work was to develop an analytical methodology to quantify vitexin in the ethanolic extract of J. mutabilis and to evaluate the expectorant and antitussive activities in mice. The expectorant activity was performed by measuring the phenol red obtained from the bronchoalveolar fluid in animals and the antitussive activity was evaluated by the cough method induced by citric acid (0.4 M). The method developed by HPLC-DAD proved to be simple, linear, precise, accurate, robust and specific. Besides, both vitexin (0.2, 1 and 5 mg/kg) and the extract of J. mutabilis (20, 102, 510 mg/kg) showed efficacy in decrease cough and increase aqueous mucus in mice, but vitexin was more potent. Lastly, the identification of vitexin opens the possibility of new studies for J. mutabilis.


Assuntos
Antitussígenos , Jatropha , Animais , Apigenina , Cromatografia Líquida de Alta Pressão , Camundongos , Extratos Vegetais/farmacologia
10.
Heliyon ; 6(12): e05461, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33305043

RESUMO

The study aimed to include the isolated vitexin of Jatropha mutabilis in the ß-cyclodextrin cavity to improve the solubility of this flavone. Its characterization was performed by techniques such as 1H NMR/ROESY (Nuclear Magnetic Resonance Spectroscopy), FT-IR (Infrared Spectroscopy with Fourier Transform), SEM (Morphological analysis of IC by Scanning Electron Microscopy) and dissolution study in vitro. In addition, the following activities were evaluated in the animal models: expectorant, phenol red dosage in bronchoalveolar lavage and antitussive, cough induced by citric acid. In the characterization of the complex, interaction between hydrogens of ring B of vitexin and (H3) of ß-CD was observed, in addition to changes in morphology. In the dissolution test, an increase in the rate of dissolution of vitexin was observed in the first 30 min for the CI vitexin/ß-CD when compared with vitexin. Regarding the pharmacological activity, it was observed that the inclusion complex (IC) vitexin/ß-CD in the equivalent doses of 0.2, 1 and 5 mg/kg of flavone presented higher expectorant activity when compared to vitexin (p < 0.05), suggesting increased bioavailability. As for the antitussive activity, both vitexin and the complex had similar effects and were dose independent. In the toxicity test using Artemia salina, vitexin and IC vitexin/ß-CD were considered non-toxic. At last, the study efficacy of vitexin/ß-CD IC as an expectorant and of vitexin as antitussive. All of these data are being described for the first time.

11.
J Ethnopharmacol ; 246: 112162, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31419501

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Lippia alnifolia Mart. & Schauer, known as "alecrim-do-mato", "alecrim-de-vaqueiro" and "pedrécio", is used in folk medicine as antiseptic and to treat diseases that affect respiratory system, like bronchitis and asthma. AIM OF THE STUDY: The aim of this work was to investigate the spasmolytic activity and relaxant mechanism of the Lippia alnifolia essential oil (EOLA) on isolated guinea-pig trachea and to correlate with its use in folk medicine. MATERIALS AND METHODS: Leaves from L. alnifolia were collected in Pico das Almas, Chapada Diamantina, situated in the city of Rio de Contas, Bahia, Brazil. EOLA was extracted by hydrodistillation, analyzed by GC/FID and GC/MS and the volatile constituents were identified. Spasmolytic activity was assayed in isolated guinea-pig trachea pre-contracted with carbachol 1 µM or histamine 10 µM. Relaxant mechanism of EOLA was determined comparing concentration-response curves in the presence or absence of different blockers. RESULTS: Chemical analysis revealed the presence of carvone (60 ±â€¯0.8%) as major constituent. EOLA (1-243 µg/mL) relaxed isolated guinea-pig trachea pre-contracted with carbachol 1 µM [EC50 = 53.36 (44.75-63.51) µg/mL] or histamine 10 µM [EC50 = 5.42 (4.42-6.65) µg/mL]. The pre-incubation of 4-aminopyridine in histamine-induced contractions did not alter significantly the relaxant effect of EOLA. However, the presence of cesium chloride, glibenclamide, tetraethylammonium, propranolol, indomethacin, dexamethasone, hexamethonium, atropine, L-NAME, methylene blue or ODQ reduced EOLA relaxant effect. EOLA 18 µg/mL pre-incubation in calcium-free medium reduced histamine-evoked contractions, but did not alter histamine contractions in the presence of nifedipine. CONCLUSIONS: Lippia alnifolia essential oil has spasmolytic activity on isolated guinea-pig trachea and its mechanism of action possibly involves the activation of multiple signal transduction pathways, which culminate in potassium channels activation and cytosolic calcium reduction.


Assuntos
Lippia , Óleos Voláteis/farmacologia , Parassimpatolíticos/farmacologia , Traqueia/efeitos dos fármacos , Animais , Cálcio/metabolismo , Carbacol/farmacologia , Monoterpenos Cicloexânicos/farmacologia , Feminino , Cobaias , Técnicas In Vitro , Masculino , Óxido Nítrico/fisiologia , Folhas de Planta , Canais de Potássio/fisiologia , Receptores Adrenérgicos beta 2/fisiologia , Traqueia/fisiologia
12.
Recent Pat Biotechnol ; 13(4): 256-267, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31237222

RESUMO

BACKGROUND: The inflammatory process is a physiological response to a vast number of harmful stimulus that takes place in order to restore homeostasis. Many drugs used in pharmacotherapy are effective to control inflammatory responses, however, there is a range of adverse effects attributed to steroidal and non-steroidal anti-inflammatory drugs (NSAIDs). In this sense, herbal medicine and derivatives have gained more attention because of their effectiveness and safety, showing the importance of medicinal plants, especially the Cannabis genus and the cannabinoid derivatives. OBJECTIVE: The aim of this prospection was to identify data related to patents involving Cannabis and cannabinoids for the treatment of inflammation. METHODS: To do so, a search for patents was conducted to evaluate the anti-inflammatory activity of Cannabis and cannabinoids. Four specialized databases for patent research were consulted using the terms "cannabis", "cannabidiol", "cannabinoids" and "THC" associated with "inflammation". RESULTS: A total of 370 patents were found, of which 17 patents met the inclusion criteria. Although reports show synergistic effects of the plant components, patents involving Cannabis and cannabinoids focus on isolated substances (CBD e THC). CONCLUSION: However, patents related to Cannabis and cannabinoids are promising for future use of the plant or its derivatives on the treatment of inflammation.


Assuntos
Anti-Inflamatórios , Canabinoides , Cannabis , Inflamação/tratamento farmacológico , Patentes como Assunto/estatística & dados numéricos , Descoberta de Drogas , Medicina Herbária , Humanos
13.
J Pharmacol Toxicol Methods ; 98: 106586, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31132413

RESUMO

INTRODUCTION: The evaluation of expectorant activity has been extensively studied in murine models, involving the secretion of phenol red in the trachea or bronchus to estimate the secretory capacity of lower airway mucosa. However, differences in the experimental protocols of several studies evidenced the need of to standardize the quantification of phenol red in the bronchoalveolar fluid (BALF). METHODS: The analytical methodology for the quantification of phenol red in the BALF was optimized by investigation of pH influence, quantity of the alkali agent added and appropriate wavelength for quantification of phenol red by UV-VIS spectroscopy. Different phenol red suspensions (0.05, 0.5, 1.25, 2.5 and 5%) were prepared and administered intraperitoneally in mice at doses 5, 25, 50, 250 or 500 mg/kg. RESULTS: It was shown that phenol red should be used at dose 500 mg/kg and intraperitoneal administration should be performed from a suspension at 1.25% (w/v). Furthermore, the alkalinizing agent of choice would be NaOH (0.1 M). The pharmacological validation of the analytical method showed that ambroxol (30, 60 or 120 mg/kg), guaifenesin (100 mg/kg), NH4Cl (2000 mg/kg) or salbutamol (4 mg/kg) can be used as positive controls. DISCUSSION: The phenol red quantification in the BALF is a rapid and low cost assay for the discovery of new expectorant drugs. Thus, it was proposed a standardization of the analytical and pharmacological methods to ensure the reliability of BALF processing and reproducibility of phenol red quantification for data analysis.


Assuntos
Expectorantes/química , Fenolsulfonaftaleína/química , Animais , Antiácidos/química , Brônquios/química , Líquido da Lavagem Broncoalveolar/química , Masculino , Camundongos , Modelos Animais , Preparações Farmacêuticas/química , Reprodutibilidade dos Testes , Traqueia/química
14.
Nat Prod Res ; 33(17): 2571-2573, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29614872

RESUMO

Lippia thymoides ('alecrim-do-mato' or 'alecrim-do-campo') is used in Brazilian folk medicine to treat various illnesses, including diarrhea. This work aimed to evaluate in vitro spasmolytic and in vivo antidiarrheal activities of the L. thymoides essential oil (OOS) and to correlate with the traditional use of this plant. In isolated guinea-pig ileum, OOS presented a concentration-dependent spasmolytic activity in preparations pre-contracted with KCl 40 mM [EC50 = 16.89 (11.56-24.66) µg/mL], and antagonized phasic contractions induced by 1 µM carbachol [IC50 = 42.71 (37.35-48.83) µg/mL] or histamine [IC50 = 32.38 (27.44-38.20) µg/mL]. In mice, OOS at 400 mg/kg reduced intestinal transit, at 200 and 400 mg/kg reduced total stool mass and at 400 mg/kg reduced intestinal fluid accumulation. It was shown that the antidiarrheal effect of OOS is related to the inhibition of smooth muscle contraction and may be due to the presence of major compound ß-caryophyllene in this essential oil.


Assuntos
Antidiarreicos/isolamento & purificação , Lippia/química , Óleos Voláteis/farmacologia , Parassimpatolíticos/isolamento & purificação , Animais , Antidiarreicos/farmacologia , Brasil , Diarreia/tratamento farmacológico , Cobaias , Íleo/efeitos dos fármacos , Medicina Tradicional , Camundongos , Contração Muscular/efeitos dos fármacos , Parassimpatolíticos/farmacologia , Extratos Vegetais/farmacologia
15.
J Ethnopharmacol ; 220: 16-25, 2018 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-29609011

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Lippia origanoides H.B.K. is an aromatic species used in folk medicine to treat respiratory diseases, including asthma. AIM OF THE STUDY: The aim of this work was to evaluate the relaxing potential and mechanism of action of the L. origanoides (LOO) essential oil in isolated guinea-pig trachea. MATERIALS AND METHODS: Leaves from L. origanoides were collected at experimental fields under organic cultivation, at the Forest Garden of Universidade Estadual de Feira de Santana. Essential oil was extracted by hydrodistillation, analyzed by GC/FID and GC/MS and the volatile constituents were identified. Spasmolytic activity and relaxant mechanism of LOO were assayed in isolated guinea-pig trachea contracted with histamine, carbachol or hyperpolarizing KCl. RESULTS: Chemical analysis revealed the presence of carvacrol (53.89%) as major constituent. LOO relaxed isolated guinea-pig trachea pre-contracted with KCl 60 mM [EC50 = 30.02 µg/mL], histamine 1 µM [EC50 = 9.28 µg/mL] or carbachol 1 µM [EC50 = 51.80 µg/mL]. The pre-incubation of glibenclamide, CsCl, propranolol, indomethacin, hexamethonium, aminophylline or L-NAME in histamine-induced contractions did not alter significantly the relaxant effect of LOO. However, the presence of 4-aminopyridine, tetraethylammonium or methylene blue reduced LOO effect, while the presence of dexamethasone or atropine potentialized the LOO relaxant effect. LOO pre-incubation inhibited carbachol-evoked contractions, with this effect potentialized in the presence of sodium nitroprusside and blocked in the presence of ODQ. CONCLUSIONS: The relaxant mechanism of LOO on the tracheal smooth muscle possibly involves stimulating of soluble guanylyl cyclase with consequent activation of the voltage-gated and Ca2+-activated K+ channels.


Assuntos
Lippia/química , Músculo Liso/efeitos dos fármacos , Óleos Voláteis/farmacologia , Traqueia/efeitos dos fármacos , Animais , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Cobaias , Masculino , Contração Muscular/efeitos dos fármacos , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso/metabolismo , Óleos Voláteis/isolamento & purificação , Parassimpatolíticos/isolamento & purificação , Parassimpatolíticos/farmacologia , Canais de Potássio Cálcio-Ativados/efeitos dos fármacos , Canais de Potássio Cálcio-Ativados/metabolismo , Canais de Potássio de Abertura Dependente da Tensão da Membrana/efeitos dos fármacos , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo , Guanilil Ciclase Solúvel/metabolismo , Traqueia/metabolismo
16.
Pharm Biol ; 54(1): 25-34, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-25856708

RESUMO

CONTEXT: Lippia thymoides Mart. & Schauer (Verbenaceae) is used in folk medicine to treat wounds, fever, bronchitis, rheumatism, headaches, and weakness. OBJECTIVE: This study determinates the chemical composition of essential oils from L. thymoides, obtained at during each of the four seasons and correlates with pharmacological properties. MATERIALS AND METHODS: Essential oils were obtained by hydrodistillation and analyzed by gas chromatography coupled to mass spectroscopy (GC-MS). Antioxidant activity was determined by DPPH free radical scavenging and ß-carotene bleaching methods. The antimicrobial assays were performed by minimum inhibitory concentration (MIC) and minimum microbicidal concentration (MMC) methods. Isolated rat aorta and uterus, and guinea-pig trachea were utilized to evaluate relaxant potential in pre-contracted smooth muscle. RESULTS AND DISCUSSION: Essential oils from leaves of L. thymoides had the sesquiterpene ß-caryophyllene (17.22-26.27%) as the major constituent followed by borneol (4.45-7.36%), camphor (3.22-8.61%), camphene (2.64-5.66%), and germacrene D (4.72-6.18%). In vitro assays showed that these essential oils do not have antioxidant activity, have antimicrobial selectivity to Gram-positive bacteria Staphylococcus aureus (MIC = 0.004 mg/mL and MMC = 0.26-10.19 mg/mL) and Micrococcus luteus (MIC = 0.03 mg/mL and MMC = 8.43 mg/mL), relax isolated rat aorta (EC50 = 305-544 µg/mL, with endothelium; and EC50 = 150-283 µg/mL, without endothelium), and uterus (EC50 = 74-257 µg/mL), and minor potency, isolated guinea-pig trachea. CONCLUSIONS: Lippia thymoides is a source of natural products of pharmaceutical interest, being necessary additional studies to determine the substances involved in the biological activities.


Assuntos
Lippia/química , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Óleos de Plantas/farmacologia , Estações do Ano , Resistência das Vias Respiratórias/efeitos dos fármacos , Animais , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/fisiologia , Compostos de Bifenilo/química , Relação Dose-Resposta a Droga , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Cobaias , Masculino , Testes de Sensibilidade Microbiana , Micrococcus luteus/efeitos dos fármacos , Micrococcus luteus/crescimento & desenvolvimento , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Oxirredução , Fitoterapia , Picratos/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Folhas de Planta , Óleos de Plantas/química , Óleos de Plantas/isolamento & purificação , Plantas Medicinais , Ratos Wistar , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Tocolíticos/química , Tocolíticos/isolamento & purificação , Tocolíticos/farmacologia , Traqueia/efeitos dos fármacos , Traqueia/fisiologia , Contração Uterina/efeitos dos fármacos , Útero/efeitos dos fármacos , Útero/fisiologia , Vasodilatação/efeitos dos fármacos , Vasodilatadores/química , Vasodilatadores/isolamento & purificação , Vasodilatadores/farmacologia , beta Caroteno/química
17.
Artigo em Inglês | MEDLINE | ID: mdl-25892998

RESUMO

The aim of this study was to evaluate crude extracts and fractions from leaves and stems of Lippia thymoides and to validate their use in folk medicine. In vitro antioxidant and antimicrobial activities and in vivo wound healing in rats, baker yeast-induced fever in young rats, and acute oral toxicity in mice assays were realized. The crude extracts and their dichloromethane and ethyl acetate fractions had potent radical-scavenging activity against the DPPH but were not effective in the ß-carotene bleaching method. The dichloromethane fraction from the leaves extract showed the broadest spectrum of activity against S. aureus, B. cereus, and C. parapsilosis. The animals treated with crude extracts showed no difference in wound healing when compared with the negative control group. The crude extract from leaves (1200 mg/kg) has equal efficacy in reducing temperature in rats with hyperpyrexia compared to dipyrone (240 mg/kg) and is better than paracetamol (150 mg/kg). In acute toxicity test, crude extract of leaves from Lippia thymoides exhibited no mortality and behavioral changes and no adverse effects in male and female mice. This work validates the popular use of Lippia thymoides for treating the wound and fever, providing a source for biologically active substances.

18.
J Therm Biol ; 42: 1-8, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24802142

RESUMO

The aim of this study was to establish the skin temperature (Tsk) thermal profile for the Brazilian population and to compare the differences between female and male Brazilian adults. A total of 117 female and 103 male were examined with a thermographic camera. The Tsk of 24 body regions of interest (ROI) were recorded and analyzed. Male Tsk results were compared to female and 10 ROI were evaluated with respect to the opposite side of the body (right vs. left) to identify the existence of significant contralateral Tsk differences (ΔTsk). When compared right to left, the largest contralateral ΔTsk was 0.3°C. The female vs. male analysis yielded significant differences (p<0.05) in 13 of the 24 ROI. Thigh regions, both ventral and dorsal, had the highest ΔTsk by sex (≈1.0°C). Tsk percentile below P5 or P10 and over P90 or P95 may be used to characterize hypothermia and hyperthermia states, respectively. Thermal patterns and Tsk tables were established for Brazilian adult men and women for each ROI. There is a low Tsk variation between sides of the body and gender differences were only significant for some ROIs.


Assuntos
Temperatura Corporal , Temperatura Cutânea , Adulto , Brasil , Feminino , Humanos , Masculino , Fatores Sexuais , Termografia , Adulto Jovem
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