Antitussive Action Research Articles

ВОЗМОЖНОСТИ ТЕРАПИИ КАШЛЯ У ДЕТЕЙ

Acute respiratory infections (ARI) are the main reason for morbidity in childhood. In ca. 90% of cases, they are accompanied by cough. The purpose of this research was to study the effectiveness and safety of the STODAL® drug in the treatment of cough in children. Materials and methods used: a multicenter prospective observational non-randomized clinical study was conducted involving 1000 outpatients with ARI aged 2 to 7 y/o and whose cough duration did not exceed 3 days from the onset of the disease. All of them were prescribed and treated with the complex homeopathic anticough drug on the day of their visit to pediatric practitioner in the outpatient hospital facilities. The patients were divided into two age groups as follows: G1 (n=500) of children aged 2 to 4 y/o and G2 (n=500) of children aged 4 years and 1 day old to 7 y/o. Results: on the 7th day of the therapy, a statistically significant decrease in the severity of daytime cough was noted: in G1 the severity of cough decreased by 1.51 points (from 2.16 to 0.65 points, p<0.001) and by 1.56 points (from 2.24 to 0.68 points, p<0.001) in G2. There was no difference in the reduction in daytime cough severity between the groups (p=0.158). The severity of night cough in G1 decreased by 1.16 points (from 1.64 to 0.48 points, p<0.001) and by 1.25 points (from 1.71 to 0.46 points, p<0.001) in G2. There were no differences in the dynamics of the severity of night cough between the groups as well (p=0.135). The proportion of patients whose cough resolved completely or became clinically insignificant on the 7th day of treatment was 98%, these patients were therefore considered recovered. Cough treatment was rated positively by 95.1% of parents/caretakers. Adverse events (AEs) were reported in 5 patients (0.5% of all cases) and there were no serious AEs among them. Conclusion: the effectiveness and safety of the STODAL® drug in the treatment of cough in ARI in children aged 2 to 7 y/o allows recommending a homeopathic drug with complex anti-inflammatory, antitussive and antimicrobial action for its inclusion in the treatment regimens starting from the first days of the disease.

Anti-Inflammatory and Antitussive Activity of Asthpadose, a Phytomedicine used in the Treatment of Asthma in Côte d'Ivoire

Introduction: The aim of this study is to contribute to the valorisation of an anti- asthmatic phytomedicine (Asthpadose) traditionally used in Côte d'Ivoire. Aims: Evalute antiasthma’s activity of the aqueous extract of Asthpadose (EAA) was. Methodology: The antiasthma’s activity of the aqueous extract of Asthpadose (EAA) was evaluated by the determining of its anti-inflammatory activity using the carrageenan oedema induction method. This anti-asthmatic activity was also evaluated by its antitussive action on the frequency of cough induced in rats exposed to liquid ammonia. Results: The results revealed that EAA showed a very significant strong anti- inflammatory activity with an oedema inhibition rate ranging from 34.29% to 70.9 5%. This activity was much better than that of diclofenac sodium (a reference molecule against inflammation) with an oedema inhibition rate ranging from 12.24% to 58.39%. As for its antitussive activity, the results also showed good antitussive activity of the extract. EAA presented a cough inhibition rate of 74.22% compared to 58.76% for dextrometaphan which is also a reference molecule against cough. Conclusion: This observed activity could therefore justify the use of Asthpadose in the treatment of asthma which is a disease manifested by inflammation and cough. In view of the very promising results of this study, it would therefore be necessary to continue studies on this phytomedicine to understand its mechanism of action on asthma.

Symptomatic treatment of cough in children

Cough is one of the most common symptoms in paediatric practice. Cough nature, duration, intensity, frequency, time and cause of occurrence should be considered in the differential diagnosis of its causes. Sputum evacuation disorders and changes in its rheological properties are indications for the prescription of mucoactive drugs. Despite the fact that the drugs included in this group have different mechanisms of action, all of them restore mucociliary clearance and lead to effective evacuation of secretions from the respiratory tract. Herbal medicinal products can be used along with classic mucoactive drugs (mucolytics, mucopegulators and mucokinetics). Ivy leaves are an example of a well-known and meticulously researched source of phytopharmaceutical products, they are included in the ESCOP monograph and entered into the positive list of the German Commission E. The efficacy and safety of ivy leaf products have been demonstrated in various controlled clinical studies. The authors presented a review of published clinical studies and non-interventional studies involving a total of 65,383 patients suffering from both acute and chronic respiratory diseases. The studies demonstrated the efficacy of ivy leaf extract preparations as achievement of a higher level of bronchodilation and surfactant production, which led to bronchospasmolytic, secretolytic, expectorant and, in turn, antitussive action. Herbal medicinal products are now actively used in the treatment of new coronavirus infection. Hedelix is one of the ivy leaf extract pharmaceutical preparations approved for use in children over the age of two years.

Effect of Adulteration on Quality and Preliminary Risk Assessment of the Decoction Pieces of Farfarae Flos Based on the Determination of Hepatotoxic Pyrrolizidine Alkaloids by UHPLC-MS/MS.

Farfarae Flos (FF) is a frequently used traditional herbal medicine with outstanding antitussive actions. The adulteration of FF decoction pieces is common. This study aimed to study the effect of adulteration on the safety and quality of FF decoction pieces. The proportion of impurities was conducted by cone quartering method. A simple and accurate ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method was established to simultaneous determinate three pyrrolizidine alkaloids (PAs) as endogenous toxic compounds in FF. The traditional medicinal parts (flower bud), impurities (pedicel and rhizome) and unselected samples were determined respectively. The values of estimated daily intake (EDI) and margin of exposure (MOE) were used for risk assessment. Twenty batches of samples were collected from different habitats, and the proportion of impurities ranged from 17.51% to 41.27%. Pedicel and rhizome were the main impurities, accounting for more than 87.40% of the total impurities. The content of PAs in impurities was significantly higher. The EDI value range was 5.34 to 16.59 μg/kg bw/day, which was much higher than the standard safety value of 7.00 × 10-3 μg/kg bw/day. The MOE values ranges for life long time and shorter exposure were 14.29 to 44.37 and 371.53 to 1153.63, respectively, indicating that at least 80% of the samples had safety risks. Correlation analysis showed that the proportion of adulterated impurities had significant correlation with the values of EDI and MOE. Adulteration of non medicinal parts may significantly increase the risk of medications of FF decoction pieces. This study provides an efficient methodology reference for the control of PAs and a basis for adulteration to affect the safety and quality of FF decoction pieces.

Malva parviflora Leaves and Fruits Mucilage as Natural Sources of Anti-Inflammatory, Antitussive and Gastro-Protective Agents: A Comparative Study Using Rat Models and Gas Chromatography.

Malva parviflora L., Little mallow, has been traditionally used as an alternative food source. It acts as a medicinal herb containing a potential source of mucilage thus herein; we aimed to assess the toxicity, anti-inflammatory, antitussive and gastro-protective actions of M. parviflora mucilage extracted from its leaves (MLM) and fruit (MFM). Toxicity studies were investigated by in vitro hemolytic assay whereas acute anti-inflammatory and antitussive activities were assessed by carrageenan-induced paw edema and sulphur dioxide induced cough model in rats, respectively. Gastro-protective effects were studied using ethanol induced acute and chronic gastric ulcer rat models. Their metabolic profiles were determined using gas chromatography. The results revealed that MLM and MFM were non-toxic towards human erythrocytes and their lethal doses were found to be greater than 5 g/kg. Pretreatment with MLM (500 mg/kg) and MFM (500 mg/kg) significantly reduced the carrageenan-induced paw thickness (p < 0.001). Maximum edema inhibition (%) was observed at 4 h in diclofenac sodium (39.31%) followed by MLM (27.35%) and MFM (15.68%). Animals pretreated with MLM (500 mg/kg) significantly lower the cough frequency in SO2 gas induced cough models in contrast to control. Moreover, MLM at doses of 250 and 500 mg/kg reduced the ethanol induced gastric mucosal injuries in acute gastric ulcer models presenting ulcer inhibition of 23.04 and 38.74%, respectively. The chronic gastric ulcer model MFM (500 mg/kg) demonstrated a remarkable gastro-protective effect showing 63.52% ulcer inhibition and results were closely related to standard drug sucralfate. In both models, MLM and MFM decreased gastric juice volume and total acidity in addition to an increased gastric juice pH and gastric mucous content justifying an anti-secretary role of this mucilage that was further confirmed by histopathological examination. Meanwhile, GC analyses of the mucilage revealed their richness with natural as well as acidic monosaccharides. It is concluded that MLM and MFM can be used therapeutically for the management of inflammation, cough and gastric ulcer.

Evidence for Alpha7 Nicotinic Receptor Activation During the Cough Suppressing Effects Induced by Nicotine and Identification of ATA-101 as a Potential Novel Therapy for the Treatment of Chronic Cough.

Studies performed in healthy smokers have documented a diminished responsiveness to tussive challenges, and several lines of experimental evidence implicate nicotine as an antitussive component in both cigarette smoke and the vapors generated by electronic cigarettes (eCigs). We set out to identify the nicotinic receptor subtype involved in the antitussive actions of nicotine and to further evaluate the potential of nicotinic receptor-selective agonists as cough-suppressing therapeutics. We confirmed an antitussive effect of nicotine in guinea pigs. We additionally observed that the alpha-4 beta-2 (α 4 β 2)-selective agonist Tc-6683 was without effect on evoked cough responses in guinea pigs, while the α 7-selective agonist PHA 543613 dose-dependently inhibited evoked coughing. We subsequently describe the preclinical evidence in support of ATA-101, a potent and highly selective (α 7) selective nicotinic receptor agonist, as a potential candidate for antitussive therapy in humans. ATA-101, formerly known as Tc-5619, was orally bioavailable and moderately central nervous system (CNS) penetrant and dose-dependently inhibited coughing in guinea pigs evoked by citric acid and bradykinin. Comparing the effects of airway targeted administration versus systemic dosing and the effects of repeated dosing at various times prior to tussive challenge, our data suggest that the antitussive actions of ATA-101 require continued engagement of α 7 nicotinic receptors, likely in the CNS. Collectively, the data provide the preclinical rationale for α 7 nicotinic receptor engagement as a novel therapeutic strategy for cough suppression. The data also suggest that α 7 nicotinic acetylcholine receptor (nAChR) activation by nicotine may be permissive to nicotine delivery in a way that may promote addiction. SIGNIFICANCE STATEMENT: This study documents the antitussive actions of nicotine and identifies the α7 nicotinic receptor subtype as the target for nicotine during cough suppression described in humans. We additionally present evidence suggesting that ATA-101 and other α7 nicotinic receptor-selective agonists may be promising candidates for the treatment of chronic refractory cough.

Features of cough therapy in children

This article discusses the problem of cough in children as one of the symptoms of a complicated course of acute respiratory infection. The data on the peculiarities of the course of cough in children depending on the cause, the level of damage, and age are presented. Virulence of infectious agents, immune status, and the child’s constitution may influence the development of local inflammation covering the tonsils, adenoids, pharynx, larynx. The study of respiratory problems in children remains relevant due to the need to improve therapy tactics and rehabilitation after an infection. Acute upper respiratory tract infections affect about 23 million children annually, which is 52% of the total morbidity of children and adolescents aged 0-17 years. Various therapeutic options are discussed. Thus, central drugs have a direct antitussive effect and cause inhibition of the cough center: narcotic antitussive drugs, such as codeine-containing drugs; non-narcotic antitussive drugs (glaucine hydrochloride, butamirate citrate, etc.). Peripheral medications reduce the sensitivity of cough afferent receptors and act on the mucosa of the airways. There are drugs of combined action, as well as bronchodilators, mucoactive drugs, and chest cough sets. Particular attention is paid to the multicomponent drug, which has a complex anti-inflammatory, antitussive and antimicrobial action in cough. The results of various foreign and domestic studies on the efficacy and safety of this drug are given. The necessity of early treatment is emphasized to improve the quality of life of patients and to prevent the formation of chronic bronchial processes. It is concluded that for the treatment of children it is necessary to choose the best drugs. It should be drugs that have proven efficacy and safety, and most importantly - they should be registered for use in the Russian Federation.

Effect of centrally and peripherally acting GABAB agonism on the healthy human cough reflex

BackgroundCurrently there are no effective licensed anti-tussive therapies. Understanding how the neuronal mechanisms mediating the cough reflex in animal models translate to humans is important for the development of effective therapies. Pre-clinical studies suggest that the activation of GABAB receptors in both the peripheral and central nervous systems inhibit cough. ObjectiveTo compare the effect of central and peripherally acting GABAB agonists (lesogaberan and baclofen) on the cough reflex in healthy volunteers. MethodsWe performed a single center, double-blind, double-dummy, three-way crossover trial in healthy controls comparing single doses of lesogaberan (120 mg MR), with baclofen (40 mg) and placebos. Cough responses to inhaled capsaicin were assessed at screening and 2h post-dose on each study day. The primary endpoint was the maximum number of coughs evoked at any concentration of capsaicin (Emax) and the secondary endpoint was the concentration evoking 50% of the maximal response (ED50). ResultsFifteen participants enrolled onto the study (median age 29 (IQR 25–44) years; 7 females, mean BMI 24.6(±3.0). Lesogaberan treatment produced a small, statistically significant increase in Emax compared with placebo [mean 13.4coughs (95%CI 10.1–17.9) vs. 11.8coughs (8.8–15.9), p = 0.04], but had no effect on ED50 [geometric mean 47.4 μM (95%CI 24.4–91.7) vs 37.6 μM (95%CI 19.2–73.5), p = 0.37]. In contrast, baclofen had no significant effect on Emax (11.1, 95%CI 8.1–15.4) (p = 0.23), but significantly increased ED50 compared with placebo (geometric mean 75.2 μM (95%CI 37.2–151.8), p = 0.002). ConclusionThis data suggests the anti-tussive actions of GABAB agonists, in healthy volunteers, occur in the central rather than the peripheral nervous system.

MORPHOLOGICAL CHANGES IN THE COLON ANASTOMOSIS AND STRESS AND AFTER SUBSEROUS ADMINISTRATION OF THE TIOTRTIAZOLINE

The article provides information that the subserous introduction of thiotriazoline creates conditions for the normal flow of regenerative processes in the anastomosis zone under conditions of chronic stress, providing antitussive and antiinflammatory action with the activation of the macrophage reaction and myofibroblasts, reducing hyperplastic and reactive and inflammatory changes, Stabilization of intracellular secretion of sialo- and sulfomutcinin in the mucous membrane of the colon, contributed to the unbreakable healing and epithelization in most of the experimental animals. The most effective indicators and noticeable effect were established at the early stages of the application of the drug.

The new possibilities for the treatment of chronic cough associated with postnasal drip

Cough is considered to be one of the leading clinical symptoms associated with the pathological changes in the respiratory system. Notwithstanding a great variety of therapeutic pharmaceutical products possessed of the antitussive action, physicians tend the give preference to the preparations producing the combined effect. The present article reports the results of the clinical study designed to evaluate the effectiveness and safety of the application of rengalin exhibiting the combined antitussive, anti-inflammatory, and broncholytic action in the patients presenting with the postnasal drip syndrome. The comparison of the therapeutic effects of rengalin with those of other therapeutic modalities frequently employed for the management of postnasal drip give evidence of the high efficiency of this product for the optimization of the treatment of this condition and the associated chronic cough.

Cough and Arabinogalactan Polysaccharide from the Bark of Terminalia Arjuna.

In this work we investigated the antitussive activity of the medicinal tree Terminalia arjuna. We used the stem bark for extraction and preparation of water extracted isolate and its two fractions: acetone-soluble (TA-S) and acetone precipitated (TA-P) fraction. The presence of a pectic arabinogalactan was confirmed in TA-P fraction by chromatographic and spectroscopic analysis. The antitussive activity of samples was assessed after oral administration in a dose of 50mg.kg(-1) in healthy guinea pigs, in which cough was elicited by inhalation of citric acid (0.3mol/L) in body plethysmograph. The water extracted isolate showed a significant ability to decrease the number of cough efforts by 64.2 %; the antitussive activity on par with that of codeine phosphate. The TA-P fraction showed the antitussive activity of 54.8 %. In contrast, TA-S fraction had only a mild antitussive activity. No changes in in vivo airway resistance were noted. We conclude that arabinogalactan is an essential component of Terminalia arjuna that underlies its antitussive action.

The effect of selective antagonist of H4 receptor JNJ7777120 on nasal symptoms, cough, airway reactivity and inflammation in guinea pigs

The efficacy of H4R antagonist JNJ7777120 on nasal symptoms, cough, airway resistance (Raw), inflammatory cell count in bronchoalveolar lavage (BAL) and blood in ovalbumin (OVA) induced allergic rhinitis (AR) was studied in guinea pigs. Animals (n=8) were sensitized by i.p. OVA and were repeatedly challenged with nasal OVA to induce rhinitis, seven animals were not sensitized. Animals were pre-treated with JNJ7777120 2.5 and 5mg/kg i.p. 30min prior OVA. Cough was induced by inhalation of citric acid, Raw was measured in vivo by Pennock's method as baseline, during AR and after JNJ7777120 treatment. Leucocyte count in BAL and blood was analyzed. JNJ7777120 (5mg/kg) significantly suppressed nasal symptoms and the number of coughs. This compound significantly inhibited airway reactivity to histamine, but not methacholine. Pre-treatment with JNJ7777120 5mg/kg did not influence significantly the leucocyte count in BAL and blood except for a significant decrease in monocyte count in blood compared to the control group (p<0.05). We conclude that the antitussive action of JNJ7777120 is peripheral. The primary effect of the compound is anti-inflammatory, and the suppression of cough is a consequence of reduced airway inflammation.

Central administration of nicotine suppresses tracheobronchial cough in anesthetized cats.

We tested the hypothesis that nicotine, which acts peripherally to promote coughing, might inhibit reflex cough at a central site. Nicotine was administered via the vertebral artery [intra-arterial (ia)] to the brain stem circulation and by microinjections into a restricted area of the caudal ventral respiratory column in 33 pentobarbital anesthetized, spontaneously breathing cats. The number of coughs induced by mechanical stimulation of the tracheobronchial airways; amplitudes of the diaphragm, abdominal muscle, and laryngeal muscles EMGs; and several temporal characteristics of cough were analyzed after administration of nicotine and compared with those during control and recovery period. (-)Nicotine (ia) reduced cough number, cough expiratory efforts, blood pressure, and heart rate in a dose-dependent manner. (-)Nicotine did not alter temporal characteristics of the cough motor pattern. Pretreatment with mecamylamine prevented the effect of (-)nicotine on blood pressure and heart rate, but did not block the antitussive action of this drug. (+)Nicotine was less potent than (-)nicotine for inhibition of cough. Microinjections of (-)nicotine into the caudal ventral respiratory column produced similar inhibitory effects on cough as administration of this isomer by the ia route. Mecamylamine microinjected in the region just before nicotine did not significantly reduce the cough suppressant effect of nicotine. Nicotinic acetylcholine receptors significantly modulate functions of brain stem and in particular caudal ventral respiratory column neurons involved in expression of the tracheobronchial cough reflex by a mecamylamine-insensitive mechanism.

P11 The Role Of Gabab Receptor Mechanisms In The Human Cough Reflex

Background Chronic cough represents an important unmet clinical need. Gamma-aminobutyric acid is a major inhibitory neurotransmitter in the central nervous system (CNS). GABA B receptors have been identified peripherally, as well as centrally. Studies in guinea-pigs, have suggested that the activation of GABA B receptors in the CNS and PNS can inhibit cough. The only clinically available GABA B agonist is Baclofen, and although it has been shown to suppress cough in animals and humans, it causes drowsiness as it is centrally acting. Lesogaberan, is a novel, predominantly peripherally acting GABA B agonist. Objective To determine whether both peripherally acting (Lesogaberan) and centrally acting (Baclofen) GABA B agonists modulate cough responses to inhaled capsaicin compared with placebo in healthy volunteers. Methods Single centre, double-blind, double-dummy, three-way crossover trial in healthy controls of Lesogaberan (120 mg MR), Baclofen (40 mg) and placebo. Subjects were treated with single doses of each study medication with a washout period of ≥7 days between doses. Cough responses to inhaled capsaicin were assessed using a novel challenge protocol (1) measured at screening and 2 hrs post dosing (tmax) on each study day. The primary end point was the maximum number of coughs evoked at any concentration of capsaicin (Emax). The secondary end point was the concentration of capsaicin evoking 50% of the maximal response (ED50). Results There were 15 patients enrolled onto the study with a median age of 29 years old (IQR25–44); 7 female; mean BMI was 24.6 (±3.0). Lesogaberan treatment was associated with a small, statistically significant increase in Emax (mean 13.4 coughs, 95% CI 10.1–17.9) compared with placebo (11.8, 95% CI 8.8–15.9) (p = 0.04), but had no effect on ED50 (geometric mean 47.4 µM 95% CI 24.4–91.7 vs Placebo 37.6 95% CI 19.2–73.5 p = 0.37), see Figure 1. In contrast, Baclofen had no significant effect on Emax (11.1, CI8.1–15.4) (p = 0.23), but, ED50 was significantly increased compared with placebo (geometric mean 75.2 µM 95% CI 37.2–151.8 p = 0.002). Conclusion This data suggests the anti-tussive actions of GABA B agonists, against capsaicin-induced cough in healthy volunteers, occurs in the central rather than the peripheral nervous system. References Allergy Clin Immunol . 2013 Oct;132(4):847–55

Is opiate action in cough due to sedation?

Opiates have been used for cough suppression for centuries. It is unclear whether this antitussive action is due to their known sedative effects. We aimed to assess correlation between cough suppression and opiate usage. We performed a post hoc analysis of two published trials with three opioids. In study one, patients with chronic cough were treated with 4 weeks of modified release morphine sulphate (5 mg twice daily) or placebo in a double-blinded placebo-controlled fashion. Cough suppression was assessed subjectively by the Leicester Cough Questionnaire and objectively by citric acid aerosol (CAA) induced cough challenge. In study 2, normal volunteers were given single doses of placebo, codeine 30 mg or dextromethorphan 50 mg and cough suppression assessed using the CAA-induced cough challenge. Sedation was contemporaneously assessed by direct questioning. There were 14 episodes of patient-reported sedation; 2 with modified release morphine sulphate, 9 with codeine and 3 with dextromethorphan. There was no correlation between change in the Leicester Cough Questionnaire or the CAA-induced cough challenge and reported sedation. This observational study suggests that sedation is unlikely to underlie the antitussive properties of these opioids. Eliciting the mechanism of these medications in cough may be a target for future tailored drug development.

Study on the antibacterial activity of Bergenia purpurascens extract.

Bergenia purpurascens has tonic, haemostatic and anti-tussive actions. Anti-inflammatory and anti-bacterial activities of Bergenia purpurascens have not been reported so far. The objective of this paper is to provide experimental basis for the clinical application of Bergenia purpurascens through the pharmacodynamic study on its anti-inflammatory and anti-bacterial effects. Experimental models of xylene-induced ear edema in mice, cotton pellet granuloma in rats, and acetic acid-induced peritoneal capillary permeability in mice were used to investigate the anti-inflammatory effect of Bergenia purpurascens; bacteriostatic and bactericidal effects of Bergenia purpurascens extract on Staphylococcus aureus (SA), methicillin-resistant Staphylococcus aureus (MRSA), and β-lactamase positive Staphylococcus aureus (ESBLs-SA), were observed in vitro. The results show that Bergenia purpurascens extract could markedly inhibit xylene-induced mouse ear edema, cotton pellet granulation tissue hyperplasia, and increased capillary permeability. Bergenia purpurascens extract has an inhibitory effect on SA, MRSA and ESBLs-SA. We conclude that Bergenia purpurascens extract has certain anti-inflammatory and anti-bacterial effects.

Antitussive activity of Withania somnifera and opioid receptors.

Arabinogalactan is a polysaccharide isolated from the roots of the medicinal plant Withania somnifera L. It contains 65% arabinose and 18% galactose. The aim of the present study was to evaluate the antitussive activity of arabinogalactan in conscious, healthy adult guinea pigs and the role of the opioid pathway in the antitussive action. A polysaccharide extract was given orally in a dose of 50 mg/kg. Cough was induced by an aerosol of citric acid in a concentration 0.3 mol/L, generated by a jet nebulizer into a plethysmographic chamber. The intensity of cough response was defined as the number of cough efforts counted during a 3-min exposure to the aerosol. The major finding was that arabinogalactan clearly suppressed the cough reflex; the suppression was comparable with that of codeine that was taken as a reference drug. The involvement of the opioid system was tested with the use of a blood-brain barrier penetrable, naloxone hydrochloride, and non-penetrable, naloxone methiodide, to distinguish between the central and peripheral mu-opioid receptor pathways. Both opioid antagonists acted to reverse the arabinogalactan-induced cough suppression; the reversion was total over time with the latter antagonist. We failed to confirm the presence of a bronchodilating effect of the polysaccharide, which could be involved in its antitussive action. We conclude that the polysaccharide arabinogalactan from Withania somnifera has a distinct antitussive activity consisting of cough suppression and that this action involves the mu-opioid receptor pathways.

Estudo das propriedades físico-químicas e avaliação da toxicidade aguda do extrato etanólico das folhas de Mikania glomerata Sprengel

A Mikania glomerata é uma planta pertencente à família Asteraceae que é bastante utilizada na medicina popular devido às suas ações broncodilatadora, antiasmática, expectorante e antitussígena. O objetivo do presente estudo foi determinar as propriedades físico-químicas do pó obtido a partir das folhas de M. glomerata, bem como, avaliar a toxicidade em camundongos após tratamento agudo com doses repetidas do extrato etanólico padronizado preparado a partir das folhas dessa espécie. Durante o estudo das propriedades físico-químicas do pó obtido a partir das folhas de M. glomerata foram feitas as determinações da densidade bruta e de compactação, do teor de cinzas totais, do teor de umidade, e da granulometria. De acordo com os resultados obtidos podemos sugerir que o pó pode ser usado na formulação de uma forma farmacêutica sólida. Na segunda parte do estudo foi determinada a Dose Letal 50% (DL50), bem como, realizada a análise morfológica macroscópica e avaliados a toxicidade aguda com doses repetidas e os parâmetros bioquímicos e hematológicos de camundongos. De acordo com os dados obtidos na segunda parte deste estudo podemos sugerir que o extrato etanólico pode ser usado de forma segura em humanos, uma vez que apresentou valor de DL50 de aproximadamente 3000 mg Kg-1), bem como, não produziu nenhuma alteração morfológica nos principais órgãos, e nem provocou alterações nos parâmetros bioquímicos e hematológicos de camundongos.

Antitussive Efficacy and Safety Profile of Ethyl Acetate Fraction ofTerminalia chebula

Antitussive effects of ethyl acetate fraction of Terminalia chebula on sulphur dioxide (SO2) gas induced cough have been examined in mice. Safety profile of Terminalia chebula was established by determining LD50 and acute neurotoxicity. The result showed that extract of Terminalia chebula dose dependently suppressed SO2 gas induced cough in mice. Terminalia chebula, after i.p. administration at dose level 500 mg/kg, offered maximum cough suppressive effects; that is, number of coughs at 60 min was 12 ± 1.52 (mean ± SEM) as compared to codeine 10 mg/kg; i.p., dextromethorphan 10 mg/kg; i.p., and saline, having frequency of cough 10.375 ± 0.866, 12.428 ± 0.81, and 46 ± 2.61, respectively. LD50 value of Terminalia chebula was approximately 1265 mg/kg, respectively. No sign of neural impairment was observed at antitussive doses of extract. Antitussive effect of Terminalia chebula was partly reversed with treatment by naloxone (3 mg/kg; s.c.) while rimcazole (3 mg/kg; s.c.) did not antagonize its cough suppression activity. This may suggest that opioid receptors partially contribute in antitussive action of Terminalia chebula. Along with this, the possibility of presence of single or multiple mechanisms activated by several different pharmacological actions (mainly anti-inflammatory, antioxidant, spasmolytic, antibacterial, and antiphlegmatic) could not be eliminated.

Pharmacology and Toxicology of Extract from Arcangelisia gusanlung

Abstract Objective To study the pharmacology and toxicology of the extracts from Arcangelisia gusanlung (EAG). Methods The anti-inflammatory activities were investigated using various inflammatory models including ear edema induced by xylene in mice, paw edema induced by carrageenan, and cotton pellet granuloma in rats. The analgesic effect was observed in hot-plate test and writhing test in mice and the antipyretic effect was observed in rat fever model induced by yeast. The antitussive action was tested in mice by sequential method and expectorant action was evaluated by tracheal excretion of phenol red. The antidiarrhea function was observed on normal intestinal propulsion of mouse model of diarrhea induced by decoction of Sennae Folium. The toxicity was measured by toxicological experiment. Results Each dose of EAG could significantly inhibit the paw edema, cotton pellet granuloma, and intestinal propulsion. EAG significantly reduced writhing times and amount of wet manure. Obvious antipyretic action to fevered rat was observed. EAG obviously increased the tracheal excretion of phenol red and prolonged the latency of cough. No toxic reaction was shown in the observed period, and the maximum tolerance dose of mice was equivalent to 1360 times of common-used dose in human. Conclusion The clinical dosage of EAG is safe, and its anti-inflammatory, analgesia, antipyresis, antitussive, expectorant, and antidiarrhea effects are significant.