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 50 mg.kg(-1) in healthy guinea pigs, in which cough was elicited by inhalation of citric acid (0.3 mol/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.

Structural Elements and Cough Suppressing Activity of Polysaccharides from Zingiber officinale Rhizome.

Zingiber officinale is used for the management of fever, bronchial asthma and cough for thousands of years. While the link to a particular indication has been established in human, the active principle of the formulation remains unknown. Herein, we have investigated a water extracted polysaccharides (WEP) containing fraction from its rhizome. Utilizing a traditional aqueous extraction protocol and using chemical, chromatographic and spectroscopic methods a fraction containing a branched glucan and polygalaturonan in a ratio of 59:1 was characterized. This glucan, which has a molecular mass of 36 kDa, is made up of terminal-, (1,4)- and (1,4,6)-linked α-Glcp residues. Oral administration of WEP in doses of 25 and 50 mg/kg body weight significantly inhibited the number of citric acid-induced cough efforts in guinea pigs. It does not alter the specific airway smooth muscle reactivity significantly. Thus, traditional aqueous extraction method provides molecular entities, which induces antitussive activity without addiction.

The cough suppressive activity of sulfated glucuronoxylan from Fagus sylvatica L.

Hemicellulose polysaccharides represent a large group of natural renewable polymers, however, their application potency is still low. In our study a hardwood 4-O-methylglucuronoxylan was isolated by alkali peroxide extraction of Fagus sylvatica sawdust and modified into sulfated water soluble derivative (MGXS). Highly sulfated MGXS was characterized by HPLC, FTIR and NMR spectroscopies, and tested in vivo on chemically induced cough reflex and smooth muscles reactivity. Farmacological tests revealed an interesting antitussive activity of MGXS. Comparative tests with drug commonly used in a clinical practice revealed that antitussive activity of MGXS was lower than that of opioid receptor agonist codeine, the strongest antitussive drug. Furthermore, the specific reactivity of airways smooth muscle was not significantly affected by MGXS, indicating thus that the polymer is not involved in the bronchodilation process.

Antioxidant activity of herbal polysaccharides and cough reflex.

The extraction of Fallopia sachalinensis leaves resulted in two fractions (FS-1 and FS-2). Chemical and spectral analyses of samples revealed the prevalence of pectic polysaccharides with high galacturonic acid, arabinose, galactose, and rhamnose content. Arabinogalactan with a higher content of phenolic prevailed in the FS-1, whereas rhamnogalacturonan predominated in the FS-2 fraction. Both polysaccharides showed significant antioxidant activity according to DPPH and FRAP assays. Evaluation of antitussive activity in healthy adult conscious guinea pigs after oral application of 50 and 75 mg/kg of the FS-2 polysaccharide extracts showed a significant suppression of cough reflex, without an influence on specific airway resistance. The suppression of cough was comparable with that of codeine.

Influence of viscous Rhodella grisea (Rhodophyceae) proteoglycan on chemically induced cough reflex.

An algal extracellular biopolymer (over 8.5 × 10(5)Da) composed of carbohydrates (52%) and protein (∼13%) has been isolated from a red alga Rhodella grisea growing in natural conditions by concentration of water medium, alcohol precipitation, dialysis and freeze-drying. This mucilagineous biopolymer contained xylose and its 3-O- and 4-O-methyl derivatives (∼63%), galactose (∼12%), glucuronic acid (11-12%), glucose (∼5%), rhamnose (∼4%), fucose (∼3-4%) and low content of others accompaning sugars. When tested on the citric acid-induced cough and reactivity of airways smooth muscle in vivo in the test system guinea pigs, this biopolymer assigned a significant cough suppressing effect. The reactivity of airways smooth muscle was not affected indicating that expectoration effect was not suppressed by biopolymer application, which is important from the pharmacological point of view.

Antitussive and immunomodulating activities of instant coffee arabinogalactan-protein.

A low molecular mass arabinogalactan-protein (AGP) composed of galactose and arabinose with a low protein content, isolated from the instant coffee powder of Coffea arabica beans, has been tested on antitussive (in vivo) and immunomodulating (ex vivo) activities. The results of antitussive tests revealed a significant dose dependant cough-suppressive effect of coffee AGP. It was observed 30 or 60 min after AGP administration and its efficacy lasted during the entire experiment course. Immunological tests showed that AGP affected some mediators of immunocompetent cells of immune system as TNF-α, IFN-γ and IL-2 cytokines. It seems that coffee AGP is a good inductor of both pro-inflammatory cytokines TNF-α and IFN-γ, however, less potent in TNF-α induction in comparison with that of ß-D-glucan. Evident induction of TNF-α, IL-2 and IFN-γ cytokines, pro-TH1 polarization supports our conclusion about bio-immunological efficacy of AGP with an emphasis on the cellular immunity.

A beneficial influence of provinol on the reduction of allergen induced hyperreactivity in guinea pigs.

BACKGROUND: The anti-inflammatory, anti-allergic, antioxidant properties of flavonoids are known in the respiratory tract. We are interested in the role of Provinol during an allergic inflammation of the airway. OBJECTIVES: The aim of this study was to examine the influence of an acute administration of Provinol on tracheal smooth muscle reactivity in guinea pigs and to assess the involvement of nitric oxide in the mechanism of Provinol action. METHODS: This experiment was performed 14 days after the sensitization of animals by ovalbumin. In vivo, the specific airway conductance, as a tracheal smooth muscle reactivity parameter in response to bronchoconstrictor histamine, was evaluated after peroral administration of Provinol alone or together with L-NAME (N(omega)-nitro-L-arginine methyl ester). In vitro, Provinol alone or in combination with L-NAME were added into an organ baths before the supplement of direct bronchoconstrictor histamine, acetylcholine and the allergen ovalbumin in rising concentrations. The amplitude of the tracheal smooth muscle contraction, as a tracheal smooth muscle reactivity parameter in response to histamine, acetylcholine and ovalbumin was evaluated. RESULTS: Our results showed that a Provinol has significant bronchodilatory activities both in vivo and in vitro. CONCLUSION: Provinol alleviated the contraction of tracheal smooth muscle in guinea pigs sumin. Nitric oxide plays an important role in the mechanism of Provinol action (Fig. 2, Ref. 28n.(Fig. 2, Ref. 28).

Possible mechanisms of dose-dependent cough suppressive effect of Althaea officinalis rhamnogalacturonan in guinea pigs test system.

The rhamnogalacturonan, isolated from the roots of medicinal plant Althaea officinalis L., showed various biological effects on the citric acid-induced cough reflex and reactivity of airways smooth muscle in vitro and in vivo conditions. It possessed dose-dependent cough suppression effect comparable with opioid agonist codeine. However, reactivity of the airways smooth muscle, measured in vitro as well as in vivo conditions was not significantly affected by rhamnogalacturonan and thus bronchodilatory activity did not participate in the cough suppression effect of polysaccharide tested. Moreover, the cough suppression effect of the polymer was not significantly modified by pretreatment of K(+)(ATP) ion channels with selective antagonist and therefore activation of this type of ion channels is not involved in the mechanism of rhamnogalacturonan cough suppressive ability. On the contrary, pretreatment of animals with selective 5-HT(2) receptors antagonist significantly decreased rhamnogalacturonan antitussive efficacy. From this point of view it seems that the cough suppression effect of the polymer is associated with the serotonergic 5-HT(2) receptor's function.

Antitussive activity of polysaccharides isolated from the Malian medicinal plants.

From the leaves of popular Malian medicinal plants Trichilia emetica (TE) and Opilia celtidifolia (OC), and fruits of Crossopteryx febrifuga (CF) water and water-ethanol soluble polysaccharide materials were isolated. The results of chemical analysis of the crude polysaccharides showed the dominance of the arabinogalactan ( approximately 54%) and the rhamnogalacturonan ( approximately 30%) in T. emetica leaves, the arabinogalactan ( approximately 60%), the rhamnogalacturonan ( approximately 14%) and the glucuronoxylan ( approximately 14%) in O. celtidifolia leaves, and pectic type of polysaccharides ( approximately 75%) with a lower content of the arabinogalactan ( approximately 17%) in C. febrifuga fruits. The plant polysaccharides showed various biological effects on the citric acid-induced cough reflex and reactivity of airways smooth muscle in vivo conditions. T. emetica and O. celtidifolia polysaccharides possessed significant cough-suppressive effect on chemically induced cough. Furthermore, values of specific airways resistance pointed on bronchodilatory property of polysaccharides isolated from O. celtidifolia. However, the crude extract from C. febrifuga in the same dose as T. emetica and O. celtidifolia did not influence the experimentally induced cough as well as reactivity of airways smooth muscle despite of the fact that the water-ethanol extract is recommended for cough therapy in Mali in the form of syrup.

Neoplastic effects of exemestane in premenopausal breast cancer model.

Aromatase inhibitor exemestane as a single - agent has no established role in the treatment of premenopausal breast cancer women. The aim of this study was to evaluate preventive effects of exemestane in the model of premenopausal Nmethyl- N-nitrosourea - induced mammary carcinogenesis in female rats. Exemestane treatment begun 7 days prior to carcinogen administration and continued next 12 weeks - till the end of experiment. Exemestane was dietary administered in two concentrations of 1 mg / 1kg (EXE 1), or 10 mg/1 kg (EXE 10), respectively. Exemestane increased the tumor frequency by 80.5 % (P=0.034) in the group EXE 1 and by 61.5 % (P=0.045) in the group EXE 10 in comparison with control animals. In the group EXE 10, the incidence of mammary tumors was increased by 11.5 % (P=0.31) and tumor volume by 41.5 % (P=0.23), also the latency was shortened by 8 days (P=0.078) compared with controls. In the groups with exemestane, changes in weights and histology of uterus and vagina were not found at the end of experiment. Exemestane did not alter serum concentrations of estradiol, testosterone and dehydroepiandrosterone. In the group EXE 10 in comparison with untreated animals, exemestane decreased serum concentrations of triacylglycerols by 9 % (P=0.032), total cholesterol by 19.5 % (P=0.0002) and cholesterol of low - density and high - density lipoprotein fractions by 41 % (P<0.0001), or 21.5 % (P=0.0002), respectively. In the group EXE 1, the decrease in cholesterol of low-density lipoprotein fraction by 22.5 % (P=0.0005) was recorded. An increase in food intake (P=0.023) and body weight gain (P=0.036) was found in the group EXE 10 compared with the control group (P<0.05). The present study points to apparent tumor - promoting effects of dietary administered exemestane in the model of premenopausal mammary carcinogenesis in female rats. Exemestane as a steroidal agent indicated androgenic effects on rat lipid metabolism in this experiment.

Relation of L-arginine to airway hyperreactivity.

The deficiency or the decrease in the bioavailability in basic substrate for nitric oxide synthesis - L-arginine can be one of factors contributing to the airway hyperreactivity. We studied the influence of L-arginine supplementation on the experimental airway hyperreactivity induced in guinea pigs by exposure to toluene vapours. L-arginine was administered before exposure in a dose of 300 mg/kg b.w. intraperitoneally during 3 or 17 days. After that the airway reactivity changes to histamine or acetylcholine were studied in in vitro conditions. In addition to that the tissue strips from exposed animals were incubated with L-arginine in concentration 10(-4) mol/l. The administration of L-arginine during 3 days decreased the airway reactivity increased by irritant exposure. We recorded the decrease in the airway reactivity in animals with bronchial hyperreactivity after incubation of tissue strips with L-arginine, too. The pre-treatment of animals with L-arginine during 17 days did not affect the airway smooth muscle reactivity in larger extent. The exogenous administration of L-arginine resulted in a protective effect under the conditions of experimental airway hyperreactivity. The effect of supplementation was different depending on airway level and pre-treatment duration. The results refer to the importance of optimal L-arginine level for the control of bronchomotoric tone.

The antitussive activity of polysaccharides from Althaea officinalis l., var. Robusta, Arctium lappa L., var. Herkules, and Prunus persica L., Batsch.

BACKGROUND: The therapy of pathological type of cough presents serious medical problem. OBJECTIVES: The aim of experiments was to investigate polysaccacharide influence on experimentally induced cough. METHODS: The purified and/or modified polysaccharides from the flowers and plants, characterized by chemical composition and molecular properties were subjected to tests for antitussive activity on cough, induced mechanically in conscious cats of both sexes. RESULTS: The results revealed that the tested polysaccharides exhibited statistically significant cough-suppressing activity, which was noticeably higher than that of the non-narcotic drug used in clinical practice to treat coughing. The most expressive antitussive activity was observed with the polysaccharide from marsh mallow, containing the highest proportion of the uronic acid constituent. Negative influence of the tested compounds on expectoration was negligible when compared to that of codeine. CONCLUSION: Antitussive activity of various plant polysaccharides was confirmed. These results allow ranging them among prospective antitussive agents (Tab. 2, Fig. 6, Ref. 15) Full Text (Free, PDF) www.bmj.sk.

Effects of antitussive drugs under normal and pathological conditions.

The antitussive effect codeine and 1-propoxyphene have been studied in non-anaesthetized healthy cats and cats with respiratory tract inflammation elicited by undiluted croton oil. The drugs were administered intraperitoneally in doses of 10 and 20 mg/kg body weight. The antitussive effect was studied on the 4th day, after inflammation had set in. Cough induced in nonanaesthetized cats by mechanical irritation of the laryngopharyngeal and tracheobronchial areas was evaluated by changes of the lateral tracheal pressure. Experimentally induced inflammatory changes of the respiratory tract due to the antitussive activity of 1-porpoxyphene were significantly reduced, but that of codeine had not changed at all.