Dieta Hoodia

By Nosalova, G; Sutovska, M; Mokry, J; Kardosova, A; Et al

Aim. The aim of our experiments was to prove the influence of herbal polysaccharide constituents on the cough reflex.

Methods. Antitussive activity of the selected plant carbohydrate substances was tested on conscious cats by mechanical stimulation of the laryngopharyngeal and tracheobronchial mucous areas of the airways through a surgically implanted endotracheal cannula. Parameters of the cough reflex (number of cough efforts, cough frequency, intensity of the maximal cough effort and intensity of the coughing attack during inspiration and during expiration) were registered and statistically evaluated. Comparative tests with commonly used antitussive drugs from both groups, narcotic (codeine) and non-narcotic (dropropizine) were carried out under the same conditions.

Results. The cough suppressive ability of polysaccharide compounds originating from the following plants was shown: Aloe vera, Althaea officinalis, Arctium lappa, Mahonia aquifolium, Malva maurltiana, Salvia officinalis and Verbascuni thapsiforme. Comparison with the same properties of the classical drugs revealed antitussive effects lower than codeine but significantly higher or similar to dropropizine. Expectoration parameters were reduced minimally after orally administered herbal agents. Side effects on plant constituent administration were rare and less serious than evidenced when codeine was applied.

Conclusion. The described impressive antitussive activity and certified adverse reactions are the reason "why the herbal compounds are to be considered as prospective drugs able to influence the cough reflex.

KEY WORDS: Cough * Antitussive activity * Herbal polysaccharides * Codeine * Dropropizine * Rhamnogalacturonan * Conscious cats.

Coughing is a powerful physiological protective and clearing mechanism of the airways which can be induced by a variety of inhaled substances and released mediators or by mechanical irritation of vagal nerve endings of the airway mucosa. Coughing is also the most common symptom of respiratory tract disorders.1-2 The cough reflex, however, can become excessive and inappropriate during exacerbations of many airway diseases.3

The pharmacological modulation of pathological coughing is still unsatisfactory despite the advanced research and the huge number of papers published on experimental results. The attractiveness of this field of investigation is based on the fact that the most active antitussive drugs, especially the group of opiate agonists with the main member codeine, belong to drugs with numerous severe side effects. Some of them, such as increased viscosity and elasticity of the mucus, inhibition of cilia motion, and worsened expectoration, are unwanted during inflammatory airway diseases, usually coupled with excessive cough. Opiate agonists are not suitable for long- term treatment of coughing because of another serious adverse effect: possibility of drug dependence.

Today's worldwide trend focused on the reduction of codeine transcription and its substitution for other drugs is associated with the renaissance of herbal medicine. Thanks to the presence of various compounds able to promote expectoration, to change the quantity and quality of the produced mucus or to normalize airway mucosa pathological conditions, the agents of plant origin seem to be very useful especially during airway inflammation associated with coughing. Recent advances in pharmacological technologies make it possible to postulate the modern trend in phytopharmacology and phytotherapy. This is based on the identification of compounds responsible for cough suppression, subsequent experimental verification of their biological properties, including quantification of the doses make it possible for rational treatment and adverse effects, too.

The basic mechanisms of action of herbal antitussives may be the same as those of orthodox antitussives: central or peripheral cough suppression. The cough reduction achieved by herbal agents is connected with their local anaesthetic, spasmolytic, antibacterial and antiviral properties. The modulation of mucus production and quality is very important, too.

From the pharmacological point of view, for the antitussive and expectorant effects of herbal medicinal products, the following active substances are responsible: saponins, alkaloids, flavonoids, terpenoids, tannins, and plant polysaccharides. Our experimental work has been concerned with herbal polysaccharides for more than 20 years. We have achieved some priority results in this field of pharmacological research. We have taken part in studies focused on evaluation of new pharmacodynamic properties of chosen plant polysaccharides and our results also have clinical implications, represented by natural medicinal products viable in the pharmacy network.

This article presents a review of our experimental findings on suppression of induced coughing by plant agents. We would like to offer the results of our phytopharmacological studies in alphabetical order of the plant sources.

Materials and methods

Plants materials

The aloe vera (Aloe barbadensis Miller) leaves were harvested on the plantation in Tambon WangNamKiew, Kumpanseng Nakon Prathon Province, Thailand, belonging to Bangkok Aloe Ltd. 23/1 Mooy workshop producing aloe vera beverages.

From the mucilaginous compact gel of the aloe leaves, homogenized to a moderately viscous liquid and filtered to discard the fibrous residue, a crude product was obtained by precipitation with isopropanol. Purification of the product by reprecipitation in the same conditions gave the polysaccharide (HF1-Z) used for the antitussive activity tests.

The polysaccharide is an acetylated (1[arrow right]4)-β-D- mannan bearing D-galactosyl residue on C-6 of the chain mannosyl units (unpublished results).

Althaea officinalis L. was obtained from the Center for the Cultivation of Medicinal Plants, Faculty of Medicine, J. E. Purkyn University, Brno, Czech Republic.

From the roots of the plant a crude mixture of polysaccharides was obtained by water extraction (complex water extract), followed by ethanol precipitation of the water extract and dialysis of the precipitate (mucilage). The three main polysaccharide components, i.e. arabinan, glucan, and rhamnogalacturonan were isolated from the mucilage by various purification methods.4, 5

Burdock (Arctium lappa L., var. Herkules) was obtained from CPN, Ltd., a company producing polysaccharides, Usti nad Orlici, Czech Republic.

From the burdock leaves the crude polysaccharide was obtained by water extraction, followed by ethanol precipitation of the filtrate, and removal of low-molecular-weight accompanying compounds by dialysis.

The crude polysaccharide is a mixture of various polysaccharide species (LL-PS), built up of glucose, galactose, rhamnose, mannose, arabinose, fucose, xylose, and ribose, showing high molecular- weight heterogeneity (unpublished results).

From the roots of the plant a neutral linear polysaccharide was obtained by a similar isolation procedure and subsequent purification and fractionation steps. The staicture of the low- molecular-weight polysaccharide was determined as a (2[arrow right]1)-β-D-fructofuranan (AlR) of the inulin type.

The plant mahonia (Mahonia aquifolium Pursh Nutt.) was collected in the Arboretum Tesarske Mlynany (Slovakia) and identified at the Department of Pharmacognosy and Botany, Faculty of Pharmacy, Comenius University, Bratislava, where the voucher specimen has been deposited.

From the stems of the plant two acid polysaccharides were isolated by alkali extraction and ethanol precipitation, followed by purification and various fractionations of the precipitate. The first polysaccharide was a (4-Omethyl-α-D-glucurono)-D-xylan (GX).6 The second compound was a complex of two closely associated polysaccharides, namely, a glucuronoxylan and pectin (MO25K1).7

Malva mauritiana L. was purchased from Slovakofarma, Medicinal plants, Malacky, Slovakia.

From the flowers of the plant a mixture of polysaccharides was isolated by water extraction, followed by ethanol precipitation of the water extract and dialysis. The main acid heteropolysaccharide of the water extract was isolated using various chromatographic methods.8

Salvia officinalis L. was purchased from Slovakofarma, Medicinal Plants, Malacky, Slovakia.

From the aerial parts of sage, a water-soluble polysaccharide complex was isolated by cold water extraction and ethanol precipitation. The dominant polysaccharide components of the complex were arabinogalactans associated with galacturonans and/or rhamnogalacturonans.9.10

Verbascum thapsiforme was purchased from Slovakofarma, Medicinal plants, Malacky, Slovakia.

From the flowers of mullein a crude mixture of polysaccharides was isolated by water extraction and ethanol precipitation. Purification of the crude product by chromatographic methods gave a polysaccharide component built up of galactose, glucose, xylose, arabinose, mannose, and uronic acids (unpublished results).

The herbal substances were dissolved in water for injection and given orally in the doses of 50 mg.kg^sup -1^ body wt and 100 mg.kg^sup -1^ body wt, respectively. Antitussive activity of the plant constituents was compared with the same ability of opiate agonist codeine in the dose 10 mg.kg^sup -1^ body wt and with a cough suppressive effect of peripherally acting dropropizine (100 mg.kg^sup-1^ body wt). Comparative tests with classic drugs administered by intraperitoneal injection were performed in the same conditions. The doses of tested herbal substances and some drugs mostly used in clinical practice were selected according to our previous experiences.11-13

Animals

Conscious cats of both sexes weighing 2 000-4 000 g were used during the experiments. There were 8 to 10 cats in each group. Anesthetics were not applied in order to eliminate their possible effect on the cough reflex. The studies on animals were carried out in accordance with the revised Declaration of Helsinki from 1983 and with approval of the Ethics Committee of the Jessenius school of Medicine, Comenius University and Faculty Hospital in Martin (Slovakia).

Antitussive activity assay

The experimental procedure is described in detail in the monograph by Korpas etal.13 and by Nosal'ova et al.14 Briefly, cough was induced by mechanical stimulation of both laryngopharyngeal and tracheobronchial parts of airway mucosa by a nylon fiber of 0.35 mm diameter through a surgically implanted chronic endotracheal cannula. This step of the experimental procedure was carried out under general anesthesia, using thiopental administered intraperitonealIy. Standard surgical care of the operative wound was followed for the next 7 days.

We preferred the method of mechanical induction of the cough reflex because it is point stimulation and the possibility of receptor adaptation to this kind of irritation is very low. Furthermore, it simulates the physiological condition of the cough reflex onset in the best way.

The cough-related parameters were recorded on a Biograph 12-03 electromanometer as intraluminal pressure changes. We evaluated the number of cough efforts (NE), the cough frequency (NE.min^sup -1^), intensity of maximal cough effort and intensity of cough attacks during expiration (IME^sup +^, IA^sup +^) and inspiration (IME^sup - ^, IA^sup -^).

Prior to application of the tested substance, the induced-cough parameters were recorded to have the control values for each animal. The same parameters in the 0.5, 1, 2 and 5 hours intervals were registered after administration of each agent.13

Laryngopharyngeal area (LP) marked columns on figures represent the values of cough parameters from irritation of the laryngopharyngeal mucous area and tracheobronchial area (TB) marked columns those from stimulation of the tracheobronchial airway area. The range represents the standard error of the measurement (+S.E.M.).

Statistical analysis

All data obtained during experiments were evaluated using the range test of Wilcoxon and Wilcox.15 Statistically significant results are marked by asterisks. The 0.05 and lower level of probability was considered as significant.

Results

Aloe vera (Family Aloaceae)

Aloe vera gel, containing acetylated mannans as dominant constituents, applied orally in the dose of 50 mg.kg^sup -1^ body wt significantly decreased NE and intensity of IA^sup +^ and IA^sup - ^, except for values of intensity of IA^sup -^ from LP. Figures 1 and 2 show a statistically significant reduction of NE as well as of the intensity of IA^sup +^. Registered parameters from TB were suppressed more significantly than values obtained from the LP region.

Prompt onset of the effect recorded after irritation of the tracheobronchial mucous area is indicated by the first statistically significant drop 30 min after administration of polysaccharide constituents. The values in all the next measured intervals were also significantly lower than the controls.

We followed the decrease of NE and IA^sup +^ from LP 1 hour after the application of the tested substance, which continued throughout the whole experimental procedure time.

A significant reduction of parameters of intensity of IA^sup -^ from the TB area was observed only 30 min and 5 h after administration of the agent. The values of NE.min^sup -1^ and intensity of IME^sup +^ and IME^sup -^ were not affected; therefore graphical presentation is not brought out.

Althaea officinalis (Family Malvaceae) We tested antitussive activities of the following agents originating from Althaea officinalis: a) Sirupus althaea commonly used in clinical practice; b) complex water extract from marshmallow root; c) the root mucilage; d) rhamnogalacturonan, accounting for about 30% of the mucilage.

The comparison of the cough suppressive ability of the individual components showed a similar potency of Sirupus althaea, complex water extract, and mucilage to depress cough parameters (Figure 3). Furthermore, the cough suppressant activity of rhamnogalacturonan was significantly, 2.5 fold higher than the effect of previously reported compounds.5

In these experiments, rhamnogalacturonan caused a drop in all recorded parameters from the LP and TB areas of the airways. The NE was influenced significantly from the first measurement at 30 min till the last 5 hours after the orally administered constituent in the dose 50 mg.kg^sup -1^ body wt (Figure 4). A statistically significant decrease of intensity of IA^sup -^ and IA^sup +^ from both LP and TB mucous regions was evident throughout the whole experimental procedure time (Figure 5). Attenuation of the NE.min^sup -1^ was not significant. Moreover, IME during inspiration and expiration were also reduced minimally.

Figure 3.-Comparison of antitussive activity of Sirupus althaeae (Sir. Alth.: dose 1 g.kg^sup -1^ body wt), complex water extract (Wat. extr.: close 1 g.kg^sup -1^ body wt), mucilage (dose 100 mg.kg^sup -1^ body wt) and rhamnogalacturonan (Rhamno: dose 50 mg.kg^sup -1^ body wt) on a mechanically induced cough reflex in experimental conditions.

According to the remarkable cough suppressive potency of pure rhamnogalacturonan, its antitussive activity (NE, IA^sup -^ and IA^sup +^) in 30 min, 1, 2 and 5 h intervals was evaluated and compared with the same parameters of codeine (Figure 6). We found a corresponding complexion of abate and evident initial difference between efficacies of both substances diminished after 2 hours and they had completely disappeared after 5 hours.

Arctium lappa (Family Asteraceae)

We showed the cough depressant abilities of the following burdock constituents: a) a crude polysaccharide complex extracted from the leaves of burdock (LL-PS) in the doses of 50 mg.kg^sup -1^ body wt; b) the same substance in the dose 100 mg.kg^sup -1^ body wt; c) the pure AlR isolated from the roots of this plant in the dose of 50 mg.kg^sup -1^ body wt.

Comparison of the cough suppressant activity values (Figure 7) revealed, that orally administered AlR and leaves polysaccharide complex (LL-PS) in the dose of 100 mg.kg^sup -1^ body wt had an antitussive effect on mechanically elicited coughing in cats, higher than non-narcotic antitussive dropropizine, but lower than narcotic control - codeine. LL-PS marked agent in the lower dose (50 mg.kg^sup -1^ body wt) did not exhibit in significant antitussive activity.

Evaluation of fructofuranan influenced cough parameters indicated onset of effect 1 hour after application. The NE.min^sup -1^ and intensity of the IA^sup -^ only lowered after irritation of the LP area, opposite to the intensity of the IA^sup +^ registered as decreased only from the TB region. Statistical significance was not evidenced. The intensity of the maximal cough expiratory and inspiratory efforts (IME^sup +^ and IME^sup -^) stayed unchanged; therefore, graphical interpretation of these findings is not offered.

We observed a relatively high incidence of side effects, especially nausea and sedation longer than 24 hours, which occurred in more than 50% of experimental animals after application of higher a dose (100 mg.kg^sup -1^ body wt) of the polysaccharide complex from the leaves.

Mahonia aquifolium (Pursh) Nutt. (Family Berberidaceae)

The acid polysaccharides (GX, MO25-K1) isolated from the stem of Oregon grape (,Mahonia aquifolium) showed high cough-suppressive activity when applied in the dose of 50 mg.kg^sup -1^ body wt (Figures 8, 9).

Figure 8 shows that orally given glucuronoxylan [(4-O-methyl- α-D-glucurono)-D-xylan, GX] caused a statistically significant decrease of NE from TB in all measured time intervals. Values from the LP mucous area were significantly reduced after 1, 2 and 5 hours. In spite of not given picture, we found lowered NE.min^sup - 1^ and intensity of IA^sup -^ and IA^sup +^ from both LP and TB regions.

The second tested compound, acid polysaccharide MO25-K1, also attenuated the experimental cough in cats (Figure 9). A statistically significant decrease in the intensity of IA^sup -^ and IA^sup +^ lasted from 30 min throughout the whole experiment, except for IA^sup -^ measurement from both the LP and TB areas after 2 hours. A distinct influence on NE and NE.min^sup -1^ was not evidenced. Significantly reduced values of NE were obtained from the TB region 2 and 5 hours after applying the substance, while the same parameters from the LP area were influenced only after 30 min and 2 h.

We concluded, that both substances had almost minimal influence on the intensity of the maximal expiratory and inspiratory cough efforts (IME^sup +^ and IME^sup -^) values.

Malva mauritiana (Family Malvaceae)

The antitussive activity tests were performed with: a) the high mallow mucilage; b) a mucilage acid polysaccharide component - rhamnogalacturonan.

The experimental studies indicated that both compounds suppressed the cough reflex evoked from both the LP and TB areas in experimental conditions (Figure 10). However, administration of rhamnogalacturonan in a dose of 50 mg.kg^sup -1^ body wt resulted in antitussive activity 15% higher than that of the mucilage.8

Comparative experiments with drugs commonly used in clinical practice revealed, that both compounds were less effective than centrally active codeine but more efficient than the non-narcotic antitussive drug dropropizine.

Salvia officinalis (Family Lamiaceae)

Th\e sage polysaccharide extract decreased all parameters of the cough reflex. A significant reduction of NE was recorded. NE was 40% lower than controls and both areas were influenced similarly.

The values of the intensity of mainly IA^sup -^ and IA^sup +^ were significantly changed (Figure 11). We followed prompt onset of the action represented by a first drop 30 min after oral administration, especially from the tracheobronchial mucous region (TB marked columns). A statistically significant inhibition of intensity of cough attack was registered during the whole experimental period.

Unlike the cough parameters from the TB airway area, we observed later onset of the effect on intensity of cough attack from the LP region (LP marked columns) after 1 hour.

Verbascum thapsiforme (Family Scrophulariaceae)

Orally applied crude polysaccharicle, isolated from mullein, in the close of 50 mg.kg^sup -1^ body wt resulted in a statistically significant decrease in the mechanically induced cough reflex parameters from both the TB and LP mucous areas of airways in conscious cats (Figure 12).

We showed a significant decrease of NE from both the LP and TB regions starting from 30 min after administration of the compound. This effect continued in all measured time intervals. A similar significant influence on the intensity of IA^sup +^ from the LP area of the airways was obtained. Changes in the intensity of IA^sup +^ from TB mucosa were lower than controls, but only measurements after 30 min and 1 h were significantly inhibited. Among the presented herbal constituents, mullein polysaccharide complex significantly decreased the NE.min^sup -1^ and the intensity of the maximal expiratory and inspiratory cough efforts (IME- and IME+), especially from the LP area (Figure 13).

Discussion

Well known severe side effects, observed very often during treatment with most active antitussives from the opiate agonists group, prompted the attempt to try and find an ideal antitussive (substance able to reduce cough without serious adverse reaction, or which decreased its occurrence as much as possible. Because potency similar to peripheral antitussives had been found in plants, they became the subjects of our interest. Our attention was caught and still is by plant polysaccharides regarded as one of the groups of naturally occurring compounds responsible for the antitussive effect. We focused our experimental works also on possible mechanisms of these plant constituents' actions.

During experiments we preferred the method of mechanical stimulation of the airways. It is considered as an objective method suitable for registration and evaluation of qualitative and quantitative determinants of the cough reflex. A wide spectrum of recorded parameters not only evaluates the influence of tested substances on the cough reflex, but also indicates a possible principle of this activity.

According to our earlier findings, compounds with a dominant peripheral mechanism of action reduce cough frequency and have less influence on amplitude, which is determined mainly by the conditions of the cough center.13, 16-18 The NE.min^sup -1^ reflects the cough receptor activity. The amplitude of the cough reflex is closely associated with IME- and IME^sup +^ parameters, which also signify the quality of expectoration.

Results of experiments with herbal polysaccharides showed a high cough suppressive ability connected mainly with influence on NE and intensity of IA^sup +^ and IA^sup -^, which are the most important predictors of antitussive activity of any substance. Impressive values of cough suppression were obtained when rhamnogalacturonan originating from Alhaea officinalis, Salvia officinalis complex polysaccharide extract and Verbascum thapsiforme polysaccharides were administered. The comparison of its efficacy with classic antitussive drugs; both narcotic and non-narcotic, revealed that reduction of cough parameters by herbal constituents is lower than opioid agonist codeine, and significantly higher or similar to peripherally acting antitussive dropropizine (Figure 14). Moreover, the relatively large initial difference between plant compounds mentioned above decreased from measurement after 2 hours and it completely disappeared 5 hours after application. This fact could be explained by the different administration route. Codeine was applied intraperitoneally, while herbal agents were given orally.

One of the often severe and known adverse effects of codeine is the worsening of expectoration. This literature fact is accompanied by a reduction of the intensity of the maximal expiratory and inspiratory cough efforts (IME^sup -^ and IME^sup +^). We demonstrated a 74% decrease in these parameters when codeine was administered in a dose of 10 mg.kg^sup -1^. Our results showed that most plant constituents did not inhibit the intensity of IME- and IME+, except for mullein, sage and burdock leaf polysaccharicles (Figure 15).

On the other hand, guaifenesin showed a cough depressant ability experimentally as well as in clinical conditions with no negative affect on expectoration.1? We exhibited only a 15% reduction in the intensity of the maximal expiratory and inspiratory cough efforts (IME- and IME+) when guaifenesin was applied in the dose of 100 mg.kg-1. These findings, noteworthy from the clinical point of view, indicate that the tested herbal polysaccharides suppressed the cough reflex, but promoted expectoration. Remedies containing tested polysaccharides might be useful for both, productive and non- productive, cough treatment. We followed mildly reduced expectoration after carbohydrate components from sage, burdock and mullein. In spite of this fact expectoration was not influenced noticeably after whole plant extract utilization. It could be explained by the presence of terpenoids and saponins. It is known, that terpenoicls originating from sage 20 or saponins isolated from mullein can increase phlegm production and promote expectoration through the vago-vagal reflexive mechanism. Terpenoids also directly enforce the activity of the serous glands in the airways and this changes the quality of the produced mucus to easily removable.

The generally accepted basal principle of plant polysaccharide action is connected with their ability to preserve cough receptors against irritation by exogenous and endogenous tussigens. Increased production of thin phlegm is considered as one of the possible devices to achieve. Likewise, polysaccharides as saponins induce a quantity of secreted mucus by the vago-vagal reflexive mechanism. The proven attenuation of the intensity of maximal expiratory and inspiratoiy cough efforts (IME- and IME+) values coupled with administration of plant polysaccharides from Verbascum tbapsiforme, Salvia officinalis and Arctium lappa and espedaily prolonged sedation of experimental animals observed after burdock leaf polysaccharides led us to the question: is it possible to explain these findings by only the peripheral principle of the action of herbal polysaccharides? Detailed description of the herbal carbohydrate compounds action mechanism is impossible from the level of our experimental results. We assume that certain central compounds participate in the mechanism of plant polysaccharide action, but this supposition needs further investigation.

According to our results on the participation of the individual constituents of Althaea officinalis and Malva mauritiana on cough suppression, we may certify, that rhamnogalacturonan is responsible for the antitussive activities of these plants.

Polysaccharides have also been reported in the literature to possess a variety of the biological activities contributing to cough suppressive effects. From this point of view the immunomodulatory activity of the polysaccharide fraction isolated from Salvia officinalis and Mahonia aguifollium is attractive e.g. significant.6,9 The next distinguished properties are antiinflammatory 21 and antiviral activities 22 of alkaloids, which are important structural components of Arctium lappa 23 as well as of Mahonia aquifollium.24,25 Antiviral activity against influenza virus and Herpes simplex virus was also observed by Verbascum densiflorum saponins.26 We assume significant antibacterial activity showed when essences, diterpenes and flavonoicls of Salvia officinalis were examined could take part in pathological cough reflex inhibition. Antinociceptive properties of Mahonia aquifolium alkaloids 27 we considered as eminent, because the analgesic components also participate in the classical antitussive drug activity (codeine). The powerful antioxidant capacity of Salvia officinalis diterpenes, reported byjanicsak et al.,2s is also noticeable.

Conclusions

In conclusion, we can summarize that substances of plant origin, herbal polysaccharides from Aloe vera, Althaea officinalis, Arctium lappa, Mahonia aquifolliurn, Malva mauritiana, Salvia officinalis, Verbascum thapsiforme possess antitussive activities. These cough suppressive effects are higher or similar to the antitussive ability in clinical practice frequently described for dropropizine, which represents the group of peripherally acting non-narcotic antitussives.

Based on our experimental results it is clear, that rhamnogalacturonan is the main pure compound participating in the demonstrated antitussive activity of herbal polysaccharides.

The registered side effects occurring only on administration of the burdock leaf polysaccharide complex in the dose 100 mg.kg^sup - 1^ body wt were less serious than those evidenced during the therapy by opiate agonists, e.g. codeine. During antitussive activity tests of other plant polysaccharides adverse reactions to the application of tested compounds have not been observed. These results correspond to the literature data, where there is no evidence of side effects according to marshmallow or high mallow therapy. Therefore, marshmallow and highmallow containing remedies are not contraindicated during pregnancy and in pediatric practice.29 Moreover, depression of respiration, typical of narcotic antitussive drugs, during the experiments was not recorded by ourselves.

The high antitussive effect and rare adverse reactions are the reason why the herbal compounds are to be considered as prospective drugs able to influence the cough reflex.

Source: Redorbit

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