Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 660
Filtrar
1.
Biomed Chromatogr ; 34(2): e4736, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31696526

RESUMO

Chimonanthus nitens Oliv. leaf (CNOL), as a traditional Chinese medicine, has been widely used for the treatment of influenza and colds over a long history. However, the mechanism of colds related to the effects of CNOL have been little studied. In this study, the anticomplement and antitussive activities of different polarity extracts of CNOL were evaluated. Ethyl acetate extract (EAE) among different extracts not only significantly decreased cough times by 21-58% (P < 0.01), but also had anticomplement effects demonstrated by the CH50 values of 0.100 mg/ml. A total of 28 constituents (10 coumarins, 13 flavonoids and five phenolics) were identified in EAE based on the ultra-high-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry technique. Eight compounds in EAE were evaluated by an ammonia-induced cough model to reveal the antitussive mechanisms and classical anticomplement pathway. The results indicated that the antitussive effects of scopoletin, kaempferol-3-O-rutinoside and kaempferol may depend on central mechanisms and that flavonoids such as compounds of kaempferol-3-O-rutinoside and kaempferol have better anticomplementary activity than coumarins like compounds of scopolin, scopoletin and isofraxidin. Taken together, kaempferol-3-O-rutinoside and kaempferol could be important chemical markers in the present study that might be used to evaluate the quality and biological activity of CNOL.


Assuntos
Antitussígenos , Calycanthaceae/química , Proteínas Inativadoras do Complemento , Extratos Vegetais , Animais , Antitussígenos/química , Antitussígenos/farmacologia , Cromatografia Líquida de Alta Pressão/métodos , Proteínas Inativadoras do Complemento/química , Proteínas Inativadoras do Complemento/farmacologia , Tosse/induzido quimicamente , Tosse/fisiopatologia , Modelos Animais de Doenças , Cobaias , Quempferóis , Masculino , Camundongos , Camundongos Endogâmicos ICR , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Espectrometria de Massas em Tandem/métodos
2.
Molecules ; 24(13)2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31247960

RESUMO

Natural products play an important role in drug discovery. This work employed a natural product 1-methylhydantoin as the lead compound to develop novel dual-active drugs. 1-Methylhydantoin was isolated from Oviductus Ranae, which is a traditional Chinese medicine that has been used for tussive and inflammation treatment for a long time. An in silico study screened the more active 1-methylhydantoin derivatives. Antitussive assessment indicated that the newly synthesized agent had similar bioactivity with the natural product. An anti-inflammatory model used xylene induced ear edema model. At the same dosage (100 mg/Kg), the newly prepared agent had an inhibition rate 53.18% which was much higher than that of the lead compound (22.69%). The results might be ascribed to the cyclooxygenases-1 (COX-1) and cyclooxygenases-2 (COX-2) selectivity, and the fitness of the compound, and the binding pocket. The anti-particulate matter (PM 2.5) acute pneumonia was evaluated through an in vivo model constructed by nasal instillation with PM 2.5 suspension. The results of the above models suggested that this novel agent had remarkable antitussive, anti-inflammatory, and anti-PM 2.5 acute pneumonia activities.


Assuntos
Anti-Inflamatórios/farmacologia , Antitussígenos/farmacologia , Produtos Biológicos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Hidantoínas/farmacologia , Animais , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Antitussígenos/síntese química , Antitussígenos/química , Produtos Biológicos/química , Ciclo-Oxigenase 1/química , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/química , Ciclo-Oxigenase 2/metabolismo , Desenho de Drogas , Medicamentos de Ervas Chinesas/síntese química , Medicamentos de Ervas Chinesas/química , Hidantoínas/síntese química , Hidantoínas/química , Camundongos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Molecular , Ligação Proteica , Relação Estrutura-Atividade
3.
Pulm Pharmacol Ther ; 56: 15-19, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30872160

RESUMO

Activation of vagal C-fibers is likely involved in some types of pathological coughing, especially coughing that is associated with airway inflammation. This is because stimulation of vagal C-fibers leads to strong urge to cough sensations, and because C-fiber terminals can be strongly activated by mediators associated with airway inflammation. The most direct manner in which a given mediator can activate a C-fiber terminal is through interacting with its receptor expressed in the terminal membrane. The agonist-receptor interaction then must lead to the opening (or potentially closing) of ion channels that lead to a membrane depolarization. This depolarization is referred to as a generator potential. If, and only if, the generator potential reaches the voltage necessary to activate voltage-gated sodium channels, action potentials are initiated and conducted to the central terminals within the CNS. Therefore, there are three target areas to block the inflammatory mediator induced activation of C-fiber terminals. First, at the level of the mediator-receptor interaction, secondly at the level of the generator potential, and third at the level of the voltage-gated sodium channels. Here we provide a brief overview of each of these therapeutic strategies.


Assuntos
Antitussígenos/farmacologia , Tosse/tratamento farmacológico , Fibras Nervosas Amielínicas/efeitos dos fármacos , Potenciais de Ação/efeitos dos fármacos , Animais , Tosse/fisiopatologia , Humanos , Fibras Nervosas Amielínicas/metabolismo , Nervo Vago/metabolismo , Canais de Sódio Disparados por Voltagem/efeitos dos fármacos , Canais de Sódio Disparados por Voltagem/metabolismo
4.
Pulm Pharmacol Ther ; 56: 79-85, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30872161

RESUMO

Cough is a protective reflex that serves to clear the airways of excessive secretions and foreign matter and which sometimes becomes excessive, and troublesome to patients. Cough is one of the most common reasons why individuals seek medical attention. A range of drugs have been developed in the past with antitussive activity and different mechanisms of action, but there are still very few safe and effective treatments available. The poor tolerability of most available antitussives is closely related to their action on the central nervous system (CNS). An international group of experts specialized in cough met to discuss the need to identify an effective antitussive treatment with a good tolerability profile. The aim of this expert review is to increase the knowledge about the cough mechanism and the activity of levodropropizine, a peripherally acting antitussive drug.


Assuntos
Antitussígenos/administração & dosagem , Tosse/tratamento farmacológico , Propilenoglicóis/administração & dosagem , Animais , Antitussígenos/efeitos adversos , Antitussígenos/farmacologia , Tosse/fisiopatologia , Desenvolvimento de Medicamentos , Humanos , Propilenoglicóis/efeitos adversos , Propilenoglicóis/farmacologia
5.
Pulm Pharmacol Ther ; 56: 75-78, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30880151

RESUMO

Chronic cough, or cough lasting >8 weeks, is often associated with underlying medical conditions (ie, asthma, gastroesophageal reflux disease, nonasthmatic eosinophilic bronchitis, and upper-airway cough syndrome). In some patients with chronic cough, treatment of these underlying conditions does not resolve the cough (refractory chronic cough [RCC]), or none of these conditions are present (unexplained chronic cough [UCC]). Despite appropriate medical evaluation, patients with RCC or UCC frequently experience cough persisting for many years, as there are currently no targeted pharmacological approaches approved for the treatment of these conditions. However, the adenosine triphosphate (ATP)-gated P2X3 receptor, a key modulator of the activation of sensory neurons central to the cough reflex, has recently garnered attention as a potential therapeutic target for the treatment of chronic cough. Gefapixant, a first-in-class, non-narcotic, selective antagonist of the P2X3 receptor, recently demonstrated efficacy and was generally well tolerated in phase 2 clinical trials in patients with RCC, validating the utility of targeting this receptor in patients with chronic cough. On the basis of these data, 2 global phase 3 trials, with combined anticipated enrolment exceeding 2000 patients and with treatment durations of up to 1 year, have been initiated. Together, these trials will further evaluate efficacy and safety of gefapixant in the control of cough in patients with RCC or UCC.


Assuntos
Tosse/tratamento farmacológico , Antagonistas do Receptor Purinérgico P2X/farmacologia , Pirimidinas/farmacologia , Sulfonamidas/farmacologia , Animais , Antitussígenos/efeitos adversos , Antitussígenos/farmacologia , Doença Crônica , Tosse/etiologia , Tosse/fisiopatologia , Humanos , Antagonistas do Receptor Purinérgico P2X/efeitos adversos , Pirimidinas/efeitos adversos , Receptores Purinérgicos P2X3/efeitos dos fármacos , Receptores Purinérgicos P2X3/metabolismo , Sulfonamidas/efeitos adversos
6.
Pak J Pharm Sci ; 32(1(Supplementary)): 339-343, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30829213

RESUMO

Cough is the common disease condition which affects patients of every age. Numerous OTC medications available in community pharmacies however no antiviral treatment and even antibiotics has been shown to be effective without pre-existing lung infection. The treatment approach of medicinal herbs has been recognized for many decades and even longer for the treatment and prevention of cough. The aim of this study was to evaluate the safety and efficacy of Mukalbion poly herbal chewable tablets for the treatment of cough with improved palatability against a marketed brand (Poly herbal). For the formulation development of test group, the herbs were supplied by the Procurement department of Herbion Pakistan Pvt. Ltd. Althea officinalis (roots), Hedera helix (leaves) and Sisymbrium irio (seeds) were used for the manufacturing of Mukalbion (poly herbal, test group) chewable tablet. The comparative control clinical trial was carried out during a time frame of 07 months with sample size of 70 patients as per epidemiological software for sample size and each group contained 35 (±5) patients. Chewable tablets were administered and evaluated for effectiveness after 15 days of treatment. The data were collected by the patients through clinical trial questionnaire. The validated quality of life questionnaire (LCQ) was also used for assessment. The results were analyzed by applying paired sample T test by using IBM SPSS version 20.00. The p value was <0.005 at 95% confidence interval for cough variables including cough bouts, viscosity of sputum, chest congestion, sore throat and shortness of breath. The LCQ cough scale score was higher in test group as compared to control group. The test group also showed well tolerated in term of palatability. None of the patient claimed any of the side effects and no compliance were observed against the marketed brand.


Assuntos
Antitussígenos/farmacologia , Tosse/tratamento farmacológico , Preparações de Plantas/farmacologia , Adolescente , Adulto , Antitussígenos/efeitos adversos , Criança , Feminino , Humanos , Masculino , Mastigação , Pessoa de Meia-Idade , Preparações de Plantas/efeitos adversos , Comprimidos , Paladar , Resultado do Tratamento
7.
Pulm Pharmacol Ther ; 56: 56-62, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30902655

RESUMO

BLU-5937 is a small molecule that was shown to be a potent, selective and non-competitive P2X3 homotrimeric receptor antagonist. P2X3 receptors are ATP ion-gated channels located on primary afferent neurons. ATP released from damaged or inflamed tissues in the airways acts on P2X3 receptors of primary afferent neurons, triggering depolarization and action potentials that are transmitted centrally and interpreted as urge to cough. There are strong preclinical and clinical evidence supporting the role of P2X3 receptors in hypersensitization of the cough reflex, leading to chronic cough. By inhibiting P2X3 receptors on the primary sensory neurons, BLU-5937 would inhibit the hypersensitization of the cough reflex and, hence, the exaggerated cough experienced in chronic cough patients. BLU-5937 is being developed for the treatment of unexplained, refractory chronic cough. The high potency and selectivity of BLU-5937 for P2X3 homotrimeric receptors was demonstrated in vitro by inhibiting αß-meATP-evoked P2X3 or P2X2/3 receptor activity in cloned human hP2X3 and hP2X2/3 channels expressed in mammalian cells. The IC50 of BLU-5937 for hP2X3 homotrimeric and hP2X2/3 heterotrimeric receptors was established at 25 nM and >24 µM, respectively. Furthermore, BLU-5937 (500 nM) was able to block αß-meATP-induced sensitization and firing activity of isolated primary nociceptors in rat dorsal root ganglions (DRGs), through P2X3 homotrimeric receptor antagonism. In a guinea pig cough model, BLU-5937 (0.3, 3 and 30 mg/kg, oral) significantly reduced, in a dose-dependent fashion, the histamine-induced enhancement in the number of citric acid-induced coughs. BLU-5937 (3 and 30 mg/kg, oral) was also shown to reduce significantly and dose-dependently the ATP-induced enhancement of citric acid-induced coughs in the guinea pig. These anti-tussive effects were obtained at a plasma concentration known to block P2X3 homotrimeric receptors, but at concentration 50-fold lower than that required to block P2X2/3 heterotrimeric receptors. These results indicate that the anti-tussive effect of BLU-5937 is primarily mediated through the inhibition of P2X3 homotrimeric receptors. In a rat behavioral taste model, BLU-5937 (10-20 mg/kg, IP) did not alter taste perception as compared to control animals. In the same experiment, N-00588 (10-20 mg/kg, IP), a weakly selective antagonist for P2X3 versus P2X2/3 receptors, had a significant inhibitory effect on taste perception. Pharmacokinetic analysis of drug plasma concentrations showed that BLU-5937 did not affect taste function at concentrations up to 30 times the IC50 for P2X3. These results suggest that N-00588 achieved systemic concentration that blocked P2X3 and P2X2/3 receptors expressed on gustatory nerve ending innervating taste buds. The lack of effect of BLU-5937, even at high doses, on taste perception may be attributed to its higher selectivity for the P2X3 versus P2X2/3 receptors on the taste buds. The safety, tolerability and pharmacokinetic profile of BLU-5937 was assessed in a battery of preclinical studies and have revealed that BLU-5937 exhibits excellent drug-like characteristics, including good oral bioavailability, low predicted clearance in human, no blood-brain barrier permeability and high safety margin versus human predicted efficacious exposure. BLU-5937 is currently in clinical phase I development stage. In conclusion, BLU-5937 was selected as a drug candidate for the treatment of chronic cough due to its high potency and selectivity for P2X3 homotrimeric receptors, strong anti-tussive effects, excellent tolerability and predicted pharmacokinetic properties in humans.


Assuntos
Antitussígenos/administração & dosagem , Tosse/tratamento farmacológico , Antagonistas do Receptor Purinérgico P2X/administração & dosagem , Receptores Purinérgicos P2X3/efeitos dos fármacos , Animais , Antitussígenos/efeitos adversos , Antitussígenos/farmacologia , Doença Crônica , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Cobaias , Humanos , Concentração Inibidora 50 , Masculino , Antagonistas do Receptor Purinérgico P2X/efeitos adversos , Antagonistas do Receptor Purinérgico P2X/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores Purinérgicos P2X3/metabolismo , Percepção Gustatória/efeitos dos fármacos
8.
Future Microbiol ; 14: 129-137, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30672328

RESUMO

Candida albicans is involved in periodontal disease, which is influenced by sex hormones. AIM: To study the effects of the estrogen antagonist tamoxifen (TAM) on periodontal disease of oncological patients; clinical oral strains of C. albicans. PATIENTS: With periodontitis and breast cancer and other with AIDS were used. MATERIALS & METHODS: Periodontal disease was evaluated by the academy of periodontology procedures and the growth of clinical C. albicans isolates were evaluated by the Clinical and Laboratory Standards Institute techniques. RESULTS: Women who consumed TAM for more than 2 years decreased periodontitis severity. In vitro, TAM inhibited the growth of both fluconazole-sensitive and resistant C. albicans. CONCLUSION: Administered TAM chronically improves periodontal health and has antifungal activity on oral strains isolated from patients with odontologic and medical pathologies.


Assuntos
Antifúngicos/farmacologia , Neoplasias da Mama/complicações , Candida albicans/efeitos dos fármacos , Doenças Periodontais/tratamento farmacológico , Doenças Periodontais/microbiologia , Tamoxifeno/farmacologia , Antitussígenos/farmacologia , Azóis , Neoplasias da Mama/tratamento farmacológico , Candida albicans/isolamento & purificação , Candida albicans/patogenicidade , Estrogênios , Feminino , Fluconazol/farmacologia , Humanos , Hospedeiro Imunocomprometido , Bolsa Periodontal/microbiologia , Periodontite
9.
Adv Exp Med Biol ; 1160: 1-9, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30637627

RESUMO

Pathological cough is an unwanted and debilitating symptom of a range of chronic respiratory diseases. Currently used antitussive therapies are ineffective and act largely through the central nervous system, having a number of dangerous adverse effects. There is an urgent need for new, better peripherally acting antitussive drugs with minimal adverse effects. Significant progress has recently been achieved in the understanding of voltage-gated sodium channels (NaVs), which points to the biological plausibility that blocking specific NaV sybtypes (NaV1.1 - NaV1.9) in the airway sensory nerves may lead to the inhibition of pathological coughing. In this study we investigated the effect of lidocaine, a non-selective NaVs blocker, on citric acid- and capsaicin-induced cough in the awake naïve guinea pig experimental model. We found that pre-inhalation followed by continuous inhalation of nebulized lidocaine (10 mM) during citric acid (0.8 M) cough challenge was effective in suppressing the cough response (number of coughs, median [IQR]) - (5 [3.8-6.3] pre-lidocaine vs. 1 [0.3-3.8] post-lidocaine; p = 0.002, n = 11). Likewise, lidocaine during capsaicin (50 µM) cough challenge reduced the number of coughs (6 [4.1-7.9] pre-lidocaine vs. 1 [0.5-1.5] post-lidocaine; p = 0.0005, n = 12). We conclude that nebulized lidocaine effectively blocks chemically induced cough. These findings lend support to the notion that NaVs may become a novel neural target in antitussive treatment.


Assuntos
Antitussígenos , Tosse , Lidocaína , Administração por Inalação , Animais , Antitussígenos/farmacologia , Capsaicina , Tosse/induzido quimicamente , Tosse/tratamento farmacológico , Cobaias , Lidocaína/farmacologia , Lidocaína/uso terapêutico , Canais de Sódio Disparados por Voltagem/efeitos dos fármacos , Vigília
10.
Biomed Pharmacother ; 109: 120-126, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30396068

RESUMO

Napoleona vogelii is used in ethnomedicine for the treatment of asthma and cough. This study evaluated antiasthmatic and antitussive properties of its methanol leaf extract (NVE) in rodents. Phytochemical screening was conducted using established methods. Acute oral toxicity test was done in mice and guinea pigs. Ovalbumin (OA)-sensitized guinea pigs were orally pretreated with 100, 200 or 400 mg/kg/day of NVE or 0.5 mg/kg/day of salbutamol for 14 days before exposure to 0.2% histamine aerosol. Latency to preconvulsive dyspnea (PCD), tracheal fluid volume (TFV), flow rate (FR), and tracheal morphometry (TM) were evaluated. Tracheal rings from sensitized guinea pigs were tested in organ baths for antispasmodic and spasmolytic effects. Citric acid and ammonium hydroxide cough models were used to evaluate antitussive effects in guinea pigs and mice respectively. Tannins, alkaloids, flavonoids, and phenolic substances were found in NVE. LD50 values in mice and guinea pigs were greater than 5000 mg/kg. NVE caused a significant (P < 0.05) increase in the latency to PCD and a decrease in TFV in the group treated with 200 mg/kg. TM indicated a reduction in airway narrowing in NVE-treated groups. The presence of NVE significantly attenuated responses of tracheal rings to carbachol. Its addition to carbachol precontracted rings resulted in significant relaxation. Emax for calcium concentration-response was significantly (P < 0.01) decreased in the presence of NVE. Cough bouts dose-dependently decreased significantly (P < 0.05) in guinea pigs and mice. We conclude that NVE seems safe and possesses anti-asthmatic effect that involves inhibition of calcium influx. It also has antitussive properties that may be peripherally mediated.


Assuntos
Antiasmáticos/farmacologia , Antitussígenos/farmacologia , Lecythidaceae/química , Extratos Vegetais/farmacologia , Albuterol/farmacologia , Animais , Antiasmáticos/administração & dosagem , Antiasmáticos/isolamento & purificação , Antitussígenos/administração & dosagem , Antitussígenos/isolamento & purificação , Asma/tratamento farmacológico , Asma/patologia , Cálcio/metabolismo , Tosse/tratamento farmacológico , Tosse/patologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Cobaias , Masculino , Metanol/química , Camundongos , Ovalbumina/imunologia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/toxicidade , Folhas de Planta , Testes de Toxicidade Aguda
11.
Carbohydr Polym ; 198: 215-224, 2018 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-30092993

RESUMO

Microalgae occupy all territories and their products represent a rich source of phytochemicals for human being. Green microalga Dictyosphaerium chlorelloides was found to be a significant producer of the extracellular biopolymer. Dominant components of the biopolymer were found to be Gal (39 wt%) with its methyl derivatives (15 wt%), Rha (19 wt%) and Man (14 wt%). 2-OMe-Gal was found to be the major derivative while other sugars, namely 3-OMe-, 6-OMe- and 2,3-di-OMe-Gal, 3-OMe-Glc and 4-OMe-Xyl were in smaller amounts. NMR spectroscopy revealed complex structure with galactan backbone branched by sugars in furano and pyrano forms in alpha and beta configurations. NMR data of 2-OMe, 3-OMe, 2,3-OMe and 6-OMe galactoses afforded characteristic values for O-methyls in each position. Biopolymer antitussive effect was similar to that of centrally acting antitussive drugs, indicating its relatively good antitussive potential.


Assuntos
Biopolímeros/análise , Clorófitas/metabolismo , Resistência das Vias Respiratórias/efeitos dos fármacos , Animais , Antitussígenos/farmacologia , Biopolímeros/química , Biopolímeros/metabolismo , Biopolímeros/farmacologia , Tosse/tratamento farmacológico , Cobaias , Espectroscopia de Ressonância Magnética , Masculino , Peso Molecular
12.
Gen Physiol Biophys ; 37(3): 337-343, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29938679

RESUMO

In this study we report pharmacological evaluation of four newly synthetized analogues of alcoxyphenyl carbamic acid, structurally related to butamirate citrate that is frequently used as cough suppressing drug, and marked as ATK 231, ATK 241, ATK 251 and ATK 261. These agents with various modifications of the molecular structure have been tested for antitussive activity in cough induced by inhalation of aerosol of citric acid (0.3 M) over 3 minutes using conscious guinea pigs. Results revealed significant cough suppressing activity without significant influence on specific airways resistances in all tested substances. ATK 231 and ATK241 showed significantly higher total antitussive activities when compared to both codeine phosphate and butamirate citrate, while ATK 251 only comparing to butamirate citrate. We did not observe any notable adverse effects and these compounds could thus potentially represent promising new non-narcotic antitussives suitable for further studies.


Assuntos
Antitussígenos/química , Antitussígenos/farmacologia , Carbamatos/química , Carbamatos/farmacologia , Animais , Antitussígenos/uso terapêutico , Carbamatos/uso terapêutico , Tosse/tratamento farmacológico , Relação Dose-Resposta a Droga , Cobaias , Masculino
13.
J Ethnopharmacol ; 222: 171-176, 2018 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-29738848

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Seeds of Cardiocrinum giganteum var. yunnanense (Leichtlin ex Elwes) Stearn (Liliaceae), also known as Doulingzi, have been used as a folk substitute for conventional antitussive herb "Madouling" (Aristolochia species) to treat chronic bronchitis and pertussis. The active antitussive phytochemicals in C. giganteum seeds are not known. AIM OF THE STUDY: The present work aims at isolating the active phytochemicals in C. giganteum seeds and confirming their antitussive effects. MATERIALS AND METHODS: Active chemicals were isolated from C. giganteum seeds ethanol extract and identified their structures. Antitussive effects were evaluated with the cough frequency of guinea pigs exposed to citric acid. Electrical stimulation of the superior laryngeal nerve in guinea pigs was performed to differentiate the acting site of potential antitussives. RESULTS: Two racemic biflavonoids (CGY-1 and CGY-2) were isolated from C. giganteum seeds. CGY-1 was identified as (S)-2″R,3″R- and (R)-2″S,3″S-dihydro-3″-hydroxyamentoflavone-7- methyl ether, which are new compounds and firstly isolated from C. giganteum seeds. Racemic CGY-2 was identified as (S)-2″R,3″R- and (R)-2″S,3″S-dihydro-3″-hydroxyamentoflavone. Both CGY-1 and CGY-2 could significantly inhibit coughs induced by inhalation of citric acid. Further, they acted on the peripheral reflex pathway to inhibit cough after electrical stimulation of the superior laryngeal nerve in guinea pigs. CONCLUSIONS: These chemicals isolated from C. giganteum seeds showed good antitussive effects. The data provide scientific evidence to support the traditional use of C. giganteum seeds as an antitussive herbal medicine.


Assuntos
Antitussígenos/uso terapêutico , Biflavonoides/uso terapêutico , Tosse/tratamento farmacológico , Liliaceae , Extratos Vegetais/uso terapêutico , Animais , Antitussígenos/isolamento & purificação , Antitussígenos/farmacologia , Biflavonoides/isolamento & purificação , Biflavonoides/farmacologia , Ácido Cítrico , Tosse/induzido quimicamente , Tosse/fisiopatologia , Estimulação Elétrica , Feminino , Cobaias , Nervos Laríngeos/efeitos dos fármacos , Nervos Laríngeos/fisiologia , Masculino , Fitoterapia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Sementes
14.
J Ethnopharmacol ; 224: 15-26, 2018 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-29787795

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Clitoria ternatea flower is traditionally used in the treatment of respiratory disorders including bronchitis and is one of the ingredients in different Ayurvedic preparations that are used in respiratory disorders. However, till date there is no scientific report on the anti-asthmatic activity of this flower. AIM OF THE STUDY: Ethanolic extract of Clitoria ternatea flowers (ECT) was evaluated for its anti-allergy and anti-tussive potential in experimental animals. Additionally, the anti-inflammatory potential of ECT was carried out to draw a plausible mechanism of action of the drug. MATERIALS AND METHODS: In-vitro anti-asthmatic activity of ECT was evaluated in goat tracheal chain and isolated guinea pig ileum preparations. Acute and chronic anti-asthmatic activity of ECT (100, 200 and 400 mg/kg; p.o.) was estimated in histamine aerosol exposed guinea pigs and in OVA sensitized and challenged mice respectively. Anti-tussive activity of ECT (100, 200 and 400 mg/kg; p.o.) was evaluated against sulfur dioxide- and citric acid-induced cough in experimental animals. Moreover, the anti-inflammatory activity of ECT (100, 200 and 400 mg/kg; p.o.) was evaluated against carrageenan- and acetic acid-induced inflammation in rats. RESULTS: ECT attenuated histamine-induced contraction in both goat tracheal chain and isolated guinea pig ileum preparations. ECT (400 mg/kg) attenuated histamine-induced dyspnoea and OVA-induced changes in differential cell count in broncheoalveolar fluid, levels of interleukins (IL-1beta and IL-6) and immunoglobulin (OVA-sensitive IgG1) in animals. ECT (400 mg/kg) further ameliorated sulfur dioxide- and citric acid-induced cough in experimental animals. Additionally, ECT (400 mg/kg) attenuated inflammation in carrageenan and acetic acid challenged rodents. CONCLUSIONS: Standardized ECT could be considered as a potential therapeutic alternative in the management of allergy-induced asthma.


Assuntos
Antialérgicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Antitussígenos/uso terapêutico , Clitoria , Extratos Vegetais/uso terapêutico , Animais , Antialérgicos/análise , Antialérgicos/farmacologia , Anti-Inflamatórios/análise , Anti-Inflamatórios/farmacologia , Antitussígenos/análise , Antitussígenos/farmacologia , Asma/sangue , Asma/tratamento farmacológico , Asma/imunologia , Asma/patologia , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/imunologia , Dispneia/tratamento farmacológico , Edema/induzido quimicamente , Edema/tratamento farmacológico , Flores , Cabras , Granuloma/tratamento farmacológico , Cobaias , Íleo/efeitos dos fármacos , Íleo/fisiologia , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Pulmão/efeitos dos fármacos , Pulmão/imunologia , Pulmão/patologia , Masculino , Camundongos , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Fitoterapia , Extratos Vegetais/análise , Extratos Vegetais/farmacologia , Ratos , Traqueia/efeitos dos fármacos , Traqueia/fisiologia
15.
Int J Mol Sci ; 19(3)2018 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-29534535

RESUMO

Osteoarthritis (OA) is the most common joint disorder and primarily affects older people. The ideal anti-OA drug should have a modest anti-inflammatory effect and only limited or no toxicity for long-term use. Because the antitussive medication dextromethorphan (DXM) is protective in atherosclerosis and neurological diseases, two common disorders in aged people, we examined whether DXM can be protective in pro-inflammatory cytokine-stimulated chondrocytes and in a collagen-induced arthritis (CIA) animal model in this study. Chondrocytes were prepared from cartilage specimens taken from pigs or OA patients. Western blotting, quantitative PCR, and immunohistochemistry were adopted to measure the expression of collagen II (Col II) and matrix metalloproteinases (MMP). DXM significantly restored tumor necrosis factor-alpha (TNF-α)-mediated reduction of collagen II and decreased TNF-α-induced MMP-13 production. To inhibit the synthesis of MMP-13, DXM blocked TNF-α downstream signaling, including I kappa B kinase (IKK)α/ß-IκBα-nuclear factor-kappaB (NF-κB) and c-Jun N-terminal kinase (JNK)-activator protein-1 (AP-1) activation. Besides this, DXM protected the CIA mice from severe inflammation and cartilage destruction. DXM seemed to protect cartilage from inflammation-mediated matrix degradation, which is an irreversible status in the disease progression of osteoarthritis. The results suggested that testing DXM as an osteoarthritis therapeutic should be a focus in further research.


Assuntos
Antitussígenos/farmacologia , Condrócitos/efeitos dos fármacos , Dextrometorfano/farmacologia , Osteoartrite/tratamento farmacológico , Animais , Antitussígenos/uso terapêutico , Células Cultivadas , Condrócitos/metabolismo , Colágeno Tipo II/genética , Colágeno Tipo II/metabolismo , Dextrometorfano/uso terapêutico , Humanos , Quinase I-kappa B/genética , Quinase I-kappa B/metabolismo , Masculino , Metaloproteinases da Matriz/genética , Metaloproteinases da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos DBA , Suínos , Fator de Transcrição AP-1/genética , Fator de Transcrição AP-1/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
16.
Respir Physiol Neurobiol ; 257: 93-99, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29369803

RESUMO

A cholinergic system has been described in the nucleus tractus solitarii (NTS). However, no information is available on the role played by acetylcholine (ACh) in the modulation of the cough reflex within the caudal NTS that has an important function in cough regulation. We addressed this issue making use of bilateral microinjections (30-50 nl) of 10 mM ACh combined with 5 mM physostigmine as well as of 10 mM mecamylamine or 10 mM scopolamine into the caudal NTS of pentobarbital sodium-anesthetized, spontaneously breathing rabbits. Microinjections of ACh/physostigmine caused depressant effects on the cough reflex induced by mechanical and chemical stimulation of the tracheobronchial tree. They also elicited transient increases in respiratory frequency and decreases in abdominal activity. These effects were prevented by scopolamine, but not by mecamylamine. The results show for the first time that ACh exerts an inhibitory modulation of the cough reflex through muscarinic receptors within the caudal NTS. They also may provide hints for novel antitussive approaches.


Assuntos
Acetilcolina/farmacologia , Antitussígenos/farmacologia , Agonistas Colinérgicos/farmacologia , Tosse/tratamento farmacológico , Reflexo/efeitos dos fármacos , Núcleo Solitário/efeitos dos fármacos , Acetilcolina/metabolismo , Animais , Tosse/metabolismo , Masculino , Mecamilamina/farmacologia , Microinjeções , Fisostigmina/farmacologia , Coelhos , Receptores Colinérgicos/metabolismo , Reflexo/fisiologia , Escopolamina/farmacologia , Núcleo Solitário/metabolismo
17.
Respir Physiol Neurobiol ; 257: 107-114, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29337269

RESUMO

A group of 11 enzyme families of metalophosphohydrolases called phosphodiesterases (PDEs) is responsible for a hydrolysis of intracellular cAMP and cGMP. Xanthine derivatives (methylxanthines) inhibit PDEs without selective action on their single isoforms and lead to many pharmacological effects, e.g. bronchodilation, anti-inflammatory and immunomodulating effects, and thus they can modulate the cough reflex. Contrary, selective PDE inhibitors have been developed to inhibit PDE isoforms with different pharmacological effects based on their tissue expression. In this paper, effects of non-selective PDE inhibitors (e.g. theophylline) are discussed, with a description of other putative mechanisms in their effects on cough. Antitussive effects of selective inhibitors of several PDE isoforms are reviewed, focusing on PDE1, PDE3, PDE4, PDE5 and PDE7. The inhibition of PDEs suggests participation of bronchodilation, suppression of TRPV channels and anti-inflammatory action in cough suppression. Selective PDE3, PDE4 and PDE5 inhibitors have demonstrated the most significant cough suppressive effects, confirming their benefits in chronic inflammatory airway diseases associated with bronchoconstriction and cough.


Assuntos
Antitussígenos/uso terapêutico , Tosse/tratamento farmacológico , Inibidores de Fosfodiesterase/uso terapêutico , Animais , Antitussígenos/farmacologia , Tosse/enzimologia , Humanos , Inibidores de Fosfodiesterase/farmacologia
18.
Bioorg Med Chem ; 26(1): 278-284, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29224994

RESUMO

Licorice has been used as an antitussive and expectorant herbal medicine for a long history. This work evaluated the activities of 14 major compounds and crude extracts of licorice, using the classical ammonia-induced cough model and phenol red secretion model in mice. Liquiritin apioside (1), liquiritin (2), and liquiritigenin (3) at 50 mg/kg (i.g.) could significantly decrease cough frequency by 30-78% (p < .01). The antitussive effects could be partially antagonized by the pretreatment of methysergide or glibenclamide, but not naloxone. Moreover, compounds 1-3 showed potent expectorant activities after 3 days treatment (p < .05). The water and ethanol extracts of licorice, which contain abundant 1 and 2, could decrease cough frequency at 200 mg/kg by 25-59% (p < .05), and enhance the phenol red secretion (p < .05), while the ethyl acetate extract showed little effect. These results indicate liquiritin apioside and liquiritin are the major antitussive and expectorant compounds of licorice. Their antitussive effects depend on both peripheral and central mechanisms.


Assuntos
Antitussígenos/farmacologia , Tosse/tratamento farmacológico , Expectorantes/farmacologia , Glycyrrhiza/química , Fenolsulfonaftaleína/metabolismo , Extratos Vegetais/farmacologia , Administração Oral , Amônia , Animais , Antitussígenos/antagonistas & inibidores , Antitussígenos/química , Tosse/induzido quimicamente , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Expectorantes/química , Expectorantes/isolamento & purificação , Glibureto/farmacologia , Masculino , Metisergida/farmacologia , Camundongos , Camundongos Endogâmicos ICR , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Relação Estrutura-Atividade
19.
J Ethnopharmacol ; 210: 39-46, 2018 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-28842340

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Fritillariae Bulbus (Beimu in Chinese) is derived from the bulbus of many Fritillaria species (family Liliaceae), which has been used as an antitussive herb in traditional Chinese medicine for more than 2000 years. Due to the complexity of plant origins and significant variations in chemical profiles, the characterization of the profile of the major bioactive constituents and its association with pharmacological activity are important for the quality control of Beimu herbs from different origins. AIM OF THE STUDY: This study aims to investigate the distribution of major bioactive isosteroidal alkaloids in Beimu herbs of different origins and its correlation with the tracheobronchial relaxant activity. METHODS: Quantification of 7 main bioactive 5α-cevanine isosteroidal alkaloids, including ebeiedine, ebeiedinone, hupehenine, isoverticine, verticine, verticinone and imperialine, in 23 Fritillaria species was performed using gas chromatography. The relaxant effect of different extracts of 4 commonly used Beimu herbs, namely Zhe-Beimu (F. thunbergii Miq.), Chuan-Beimu (F. cirrhosa D. Don), Hubei-Beimu (F. hupehensis Hsiao et K. C. Hsia) and Yi-Beimu (F. pallidiflora Schrenk), was evaluated using rat isolated tracheal and bronchial preparations pre-contracted with carbachol, the well established in vitro antitussive model. RESULTS: Amongst 23 Fritillaria species detected, significant variations of the types and quantities of 7 major isosteroidal alkaloids were determined, which served as an important indicator for the classification of different Beimu herbs with distinct geographic distributions. Based on the type and quantity of these alkaloids, different origins of Beimu could be clearly clustered into several subgroups by principal component analysis. Furthermore, both crude alkaloid and water extracts of all 4 Beimu herbs showed a dose-dependent tracheobronchial relaxation with different potencies. The total content of alkaloids (weight adjusted based on the activity of individual alkaloids) in Beimu extracts significantly correlated with their tracheobronchial relaxation effects (r2 > 0.9, p < 0.001). CONCLUSIONS: The results demonstrated that the differences in chemical profile of major bioactive isosteroidal alkaloids and pharmacological activity of Beimu could be incorporated into a simple and unified method for quality control and potential prediction of activity of Beimu herbs from different origins.


Assuntos
Alcaloides/farmacologia , Antitussígenos/farmacologia , Fritillaria/química , Extratos Vegetais/farmacologia , Alcaloides/química , Alcaloides/isolamento & purificação , Animais , Antitussígenos/isolamento & purificação , Brônquios/efeitos dos fármacos , Cromatografia Gasosa , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Masculino , Medicina Tradicional Chinesa , Controle de Qualidade , Ratos , Ratos Sprague-Dawley , Traqueia/efeitos dos fármacos
20.
J Ethnopharmacol ; 210: 107-117, 2018 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-28811222

RESUMO

ETHNOPHARMACOLOGY RELEVANCE: Blepharocalyx salicifolius (Kunth) O. Berg (Myrtaceae) is a tree native to Argentina and Uruguay that grows and is cultivated along the riverside of the Rio de la Plata. The leaves of this plant species, locally known as "anacahuita" are used in South America to prepare infusions for the empiric treatment of cough and bronchospasm, as well as diarrhoea and other intestinal disorders. Although previous phytochemical studies have been performed with the essential oil extracted from Blepharocalyx salicifolius, pharmacological evidence supporting its traditional use is still lacking. AIM OF THE STUDY: To experimentally evaluate the pharmacological properties of Blepharocalyx salicifolius based on its traditional use. The studies were performed with tincture (T-Bs) and essential oil (EO-Bs) prepared from its leaves, in isolated rat trachea, intestine and heart preparations. METHODS: The ex-vivo effects of T-Bs and EO-Bs were evaluated with the agonists carbachol (CCh) and calcium chloride (Ca2+) in the contractile concentration-response curves (CRC) of the isolated intestine. The muscle relaxant effect of EO-Bs was evaluated in the isolated trachea and compared with the effect achieved with papaverine as a positive control. The T-Bs and EO-Bs cardiac effects were analysed by perfusion of an isolated rat heart before a period of ischemia/reperfusion (stunning model). The antitussive effect of both T-Bs and EO-Bs was evaluated in mice exposed to ammonia using codeine as a positive control. RESULTS: Both T-Bs and EO-Bs induced a non-competitive inhibition of the CCh-CRC in the rat intestine, with IC50 values of 170.3 ± 48.5µg T-Bs/mL (n = 6) and 5.9 ± 1.6µg EO-Bs/mL (n = 6), respectively. EO-Bs also inhibited non-competitively the Ca2+-CRC, with IC50 value of 1.8 ± 0.3µg EO-Bs/mL (n = 8). A similar effect was obtained with the main active component of the EO-Bs 1,8-cineole. In isolated trachea, EO-Bs induced the relaxation of the CCh-contracted tissue (1.7 ± 0.2µg EO-Bs/mL, n = 11) up to a maximal relaxation that was 1.9 times higher than that of papaverine. In the isolated heart, EO-Bs induced a poor negative inotropic response, and did not improve the contractile and energetic recovery after ischemia and reperfusion. In the mouse cough model, EO-Bs (90mg/Kg) was as effective as codeine (30mg/Kg) in reducing cough frequency. CONCLUSIONS: The results indicate that the preparations from Blepharocalyx salicifolius leaves were effective as central antitussive, bronchodilating and antispasmodic agents, suggestive of a mechanism associated with the inhibition of Ca2+ influx into smooth muscle. The EO-Bs displayed only a poor ability to reduce cardiac inotropism, and was devoid of any cardioprotective properties. Thus, the present study validates the traditional use of this South American plant for asthma, cough and bronchospasm, shedding new light into its potency and putative mechanism of action.


Assuntos
Medicina Tradicional/métodos , Myrtaceae/química , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Animais , Antitussígenos/administração & dosagem , Antitussígenos/isolamento & purificação , Antitussígenos/farmacologia , Broncodilatadores/administração & dosagem , Broncodilatadores/isolamento & purificação , Broncodilatadores/farmacologia , Cálcio/metabolismo , Cardiotônicos/administração & dosagem , Cardiotônicos/isolamento & purificação , Cardiotônicos/farmacologia , Tosse/tratamento farmacológico , Modelos Animais de Doenças , Feminino , Concentração Inibidora 50 , Masculino , Camundongos , Óleos Voláteis/administração & dosagem , Óleos Voláteis/isolamento & purificação , Parassimpatolíticos/administração & dosagem , Parassimpatolíticos/isolamento & purificação , Parassimpatolíticos/farmacologia , Extratos Vegetais/administração & dosagem , Folhas de Planta , Ratos , Ratos Sprague-Dawley , América do Sul
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA