Antitussive, Expectorant and Antipyretic Effect of the Ethanolic Extract of the Leaves of Momordica charantia L.

The traditional use of the M. charantia L. plant to treat coughs, fever and expectoration is widely practiced in different cultures, but its effectiveness and safety still require scientific investigation. This study sought to perform a chemical analysis and evaluate the antitussive, expectorant and antipyretic effects of the ethanolic extract of M. charantia leaves (EEMc) in rats and mice. The EEMc was subjected to chemical analysis by HPLC-DAD, revealing the presence of the flavonoids astragalin and isoquercetin. Acute oral toxicity in mice did not result in deaths, although changes in liver weight and stool consistency were observed. EEMc demonstrated an antitussive effect at doses of 100 and 300 mg/kg in mice subjected to cough induction by citric acid nebulization. Furthermore, it showed expectorant activity at a dose of 300 mg/kg, assessed based on the elimination of the phenol red marker in bronchoalveolar lavage. In the evaluation of antipyretic activity in rats, fever induced by Saccharomyces cerevisiae was reduced at all doses tested during the first hour after treatment. This innovative study identified the presence of astragalin and isoquercetin in EEMc and indicated that the extract has antitussive, expectorant and antipyretic properties. Therefore, EEMc presents itself as a promising option in herbal medicine for the treatment of respiratory symptoms and fever.

Chemical Analysis by LC-MS of Cannabis sativa Root Samples from Northeast Brazil and Evaluation of Antitussive and Expectorant Activities.

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.

Evaluation of cardiorespiratory and biochemical effects of ketamine-propofol and guaifenesin-ketamine-xylazine anesthesia in donkeys (Equus asinus).

OBJECTIVES: To evaluate the cardiorespiratory and biochemical effects of ketamine-propofol (KP) or guaifenesin-ketamine-xylazine (GKX) anesthesia in donkeys. STUDY DESIGN: Prospective crossover trial. ANIMALS: Eight healthy, standard donkeys, aged 10 ± 5 years and weighing 153 ± 23 kg. METHODS: Donkeys were premedicated with 1.0 mg kg(-1) of xylazine (IV) in both treatments. Eight donkeys were administered ketamine (1.5 mg kg(-1)) and propofol (0.5 mg kg(-1) for induction, and anesthesia was maintained by constant rate infusion (CRI) of ketamine (0.05 mg kg(-1) minute(-1)) and propofol (0.15 mg kg(-1) minute(-1)) in the KP treatment. After 10 days, diazepam (0.05 mg kg(-1)) and ketamine (2.2 mg kg(-1)) were administered for induction, and anesthesia was maintained by a CRI (2.0 mL kg(-1) hour(-1)) of ketamine (2.0 mg mL(-1), xylazine (0.5 mg mL(-1)) and guaifenesin (50 mg mL(-1)) solution. Quality of anesthesia was assessed along with cardiorespiratory and biochemical measurements. RESULTS: Anesthetic induction took longer in GKX than in KP. The induction was considered good in 7/8 with KP and in 6/8 in GKX. Anesthetic recovery was classified as good in 7/8 animals in both treatments. Xylazine administration decreased heart rate (HR) in both treatments, but in KP the HR increased and was higher than GKX throughout the anesthetic period. Respiratory rate was higher in GKX than in KP. PaO(2) decreased significantly in both groups during the anesthetic period. Glucose concentrations [GLU] increased and rectal temperature and PCV decreased in both treatments. Arterial lactate [LAC] increased at recovery compared with all time points in KP. [GLU] and calcium were higher in GKX than in KP at recovery. CONCLUSION AND CLINICAL RELEVANCE: These protocols induced significant hypoxemia but no other cardiorespiratory or metabolic changes. These protocols could be used to maintain anesthesia in donkeys, however, they were not tested in animals undergoing surgery.

Expectorant and antioxidant activities of purified fumarprotocetraric acid from Cladonia verticillaris lichen in mice.

UNLABELLED: The lichen Cladonia verticillaris produces bioactive secondary metabolites, such as fumarprotocetraric (FUM) and protocetraric acids. Species of the genus Cladonia demonstrate anti-tumor, anti-inflammatory and antipyretic activities and have been used in folk medicine to treat respiratory diseases (throat irritation, cough, asthma and tuberculosis). The aim of the present study was to evaluate the expectorant and mucolytic activities of fumarprotocetraric acid in albino Swiss mice. FUM was extracted and purified from an acetone extract of C. verticillaris. The phenol red quantification method was used on the bronchoalveolar lavage fluid following the administration of FUM (25, 50 or 100 mg/kg orally or intraduodenally and 12.5, 25 or 50 mg/kg, intraperitoneally) for the evaluation of expectorant activity. Control groups received either saline solution (7.5 mL/kg) or ambroxol (1 mg/kg) through the same administration routes. Antioxidant activity was evaluated using the thiobarbituric acid reactive species assay in mouse lung tissue treated with the FUM at 25, 50 or 100 mg/kg orally, followed by a lipopolysaccharide solution at 1 mg/kg intrapleurally. The same protocol was used for the control groups using either saline solution (7.5 mL/kg, orally) or N-acetylcysteine (20 mg/kg, orally). RESULTS: Orally administered FUM at doses of 25 and 50 mg/kg promoted significantly greater dose-dependent phenol red activity in the bronchoalveolar lavage and expectorant activity in comparison to the controls (p < 0.05). Lipid peroxidation (malondialdehyde equivalent) was reduced by 50% in the lung tissue. CONCLUSION: The results confirm the expectorant and antioxidant properties of fumarprotocetraric acid produced by the lichen C. verticillaris.

Concentration-dependence of dithiothreitol effects on rat distal colon electrophysiology

Dithiothreitol (DTT), at 1 mmol/L or higher, is widely used as a mucolytic in gastrointestinal research. Previous observations suggest that it may be toxic to the mucosa. DTT effects on the mucosal electrical behavior were assessed. Cumulative concentration-response relationships of DTT effects on rat distal colon mucosa were studied. Isolated mucosa preparations were mounted in an Ussing chamber under short-circuit conditions. The effects of concentrations ranging from 1 mumol/L to 1 mmol/L, applied to either the mucosal or serosal side, were studied. As compared with control, untreated preparations, DTT depressed short-circuit current at 10 mumol/L and higher when applied to the serosal side, and at 50 mumol/L and higher when applied to the mucosal side of the epithelium. On the other hand, transepithelial resistivity showed a progressive increase with DTT applied to either side at a concentration of up to 500 mumol/L, while at the highest concentration (1 mmol/L) a marked decrease in resistivity occurred. Neither the short-circuit current decrease, nor the resistivity collapse showed recovery after repeated rinsing with DTT-free solution. It is concluded that DTT affects epithelial electrical properties at low concentrations, and therefore its use as a mucolytic for electrophysiological studies should be discouraged.(AU)

Concentration-dependence of dithiothreitol effects on rat distal colon electrophysiology.

Dithiothreitol (DTT), at 1 mmol/L or higher, is widely used as a mucolytic in gastrointestinal research. Previous observations suggest that it may be toxic to the mucosa. DTT effects on the mucosal electrical behavior were assessed. Cumulative concentration-response relationships of DTT effects on rat distal colon mucosa were studied. Isolated mucosa preparations were mounted in an Ussing chamber under short-circuit conditions. The effects of concentrations ranging from 1 mumol/L to 1 mmol/L, applied to either the mucosal or serosal side, were studied. As compared with control, untreated preparations, DTT depressed short-circuit current at 10 mumol/L and higher when applied to the serosal side, and at 50 mumol/L and higher when applied to the mucosal side of the epithelium. On the other hand, transepithelial resistivity showed a progressive increase with DTT applied to either side at a concentration of up to 500 mumol/L, while at the highest concentration (1 mmol/L) a marked decrease in resistivity occurred. Neither the short-circuit current decrease, nor the resistivity collapse showed recovery after repeated rinsing with DTT-free solution. It is concluded that DTT affects epithelial electrical properties at low concentrations, and therefore its use as a mucolytic for electrophysiological studies should be discouraged.

Factors involved in the biochemical etiology of human seminal plasma hyperviscosity.

Semen rheology was studied to elucidate the biochemical basis of seminal plasma hyperviscosity. Semen proved to fit in with a power law model, by presenting a pseudoplastic behavior. Apparent viscosity at 230 s(-1) and 25 degrees C (eta(a)) was 4.3 /- 0.2 cp and 5.4 +/- 0.4 cp in normal and high-consistency semen, respectively. The effect of enzymes and mucolytic agents on human seminal plasma viscosity were evaluated by incubating normal and hyperviscous semen pool aliquots with trypsin, dithiothreitol, EDTA, alpha-amylase and deoxyribonuclease I. After incubation, trypsin treatment reduced eta(a) by 36% in normal semen and by 44% in hyperviscous semen. There was a decrease in eta(a) following incubation of hyperviscous samples with dithiothreitol (33%) and alpha-amylase (44%) that was not observed in the normal consistency samples. No decrease was observed in eta(a) after EDTA or DNAse treatment of both groups. Comparison of normal and hyperviscous seminal plasmas revealed no difference in the concentration of total proteins, DNA, or in the percentage of water content. These findings indicate that the primary substances responsible for basic normal semen rheologic behavior are proteins. A comparison of rheological properties between normal and hyperviscous semen samples indicates the existence of a highly organized network in the latter group, in which disulfide bonds and oligosaccharide chains complexed to the peptide core may play a key role.

Estudos da estabilidade da secreçäo mucóide / Stability studies of mucus secretion

O objetivo do trabalho, é a determinaçäo de parâmetros definitórios do modelo de comportamento reológico da secreçäo mucóide das expectoraçöes, analisando as variaçöes produzidas em doentes tratadas ou näo como fármacos mucolíticos. Finalmente, é estudada a estabilidade da secreçäo mucóide frente a uma açäo de fricçäo repetitiva, definido o parâmetro de caracterizaçäo (coeficiente de perda logarítmica de viscosidade por ciclo), verificando, desta forma, sua estabilidade

Tracheobronchial function in health and disease: effect of mucolytic substances

The effect of mucolytic and expectorant substances on ciliary beat frequency, mucus transport velocity and mucus production, was investigated in normal and bronchitic rats. The results showed that: (i) N-acetylcysteine and S-carboxymethylcysteine were mildly cilioexcitatory at low and ciliodepressive at higher concentrations in both normal and bronchitic rats. A similar pattern was seen in mucus transport velocity. (ii) Bisolvan enhanced all aspects of muciciliary activity in both groups of animals. Sobrepin was less effective than Bisolvan and more effective than Tachoquilin. (iii) Geleomytrol, Ozothin and prostaglandin E1 were all cilioexcitatory in rats with bronchitis. Mucus transport velocity was similarly stimulated by both Geleomyrtol and Ozothin. (iv) Ammonium chloride and potassium iodide enhanced mucociliary activity in normal and bronchitic rats. (v) All substances stimulated mucus production, however, the most potent was prostaglandins E1. The mechanisms for increased mucociliary activity involve inter alia the probable cleaving of disulphide bridges, decreased mucosal swelling, altered rheological characteristics and stimulation of adenylate cyclase (AU)