1- Shirazi Thyme: With regard to thymol and carvacrol (the main active components of Shirazi thyme), a vast spectrum of effects against bacteria involved in higher respiratory tract infections has been observed. It is believed that thymol and carvacrol exert their antibacterial effect through complex formation with bacterial membrane proteins. A synergistic effect has also been determined between thymol and carvacrol. Also, it has been shown that sufficient doses of thymol and carvacrol have relaxant effects on the trachea. Various clinical trials have confirmed the effect of thyme on productive cough. In a randomized, double-blind study, 60 patients with productive cough received either thyme syrup or bromhexine syrup for 5 days. Based on the self reports of the patients, there was no significant difference between the two groups and the both groups benefitted equally from the medication. There was significant improvement in the case of non-smokers compared to smokers in both groups. The essential oil of Shirazi thyme is effective against pathogen bacteria, especially S. aureus.
The study of the effects of Shirazi thyme on systemic inflammation in Guinea pig COPD model showed that the preventive effects of the hydroethanolic extract of Shirazi thyme on all measured parameters (like interleukin-8, malondialdehyde, WBC count and eosinophil) is comparable with, and even more than, dexamethasone.
2- Marshmallow: In in vitro and in vivo conditions, the rhamnogalacturonan isolated from marshmallow root has various biologic effects on the cough reflex and the citric acid induced excitability of smooth muscles of the respiratory tract. This compound has dose-dependent cough suppressing effects, comparable to that of codeine (narcotic agonist). However, in in vitro and in vivo conditions the excitability of the smooth muscles of the respiratory tract are not considerably affected by rhamnogalacturonan, therefore, the bronchodilator effect does not affect cough suppression. Furthermore, in the anti-cough mechanism, the activation of K+ATP ion channels also have no effect. It seems that the cough suppressing effects of the rhamnogalacturonan isolated from marshmallow root might be related to the function of 5-HT2 serotonergic receptors. (4)
Furthermore, in a study of the anti-tussive effect of rhamnogalacturonan polysaccharide isolated from marshmallow flower in Guinea pig, it became clear that marshmallow flower dose-dependently inhibits the cough reflex in non-sensitized Guinea pigs and at the same time reduces the induced allergic inflammation state in sensitized mice and the anti-tussive effects of codeine (10 mg/kg, oral) was comparable with high doses of rhamnogalacturonan in non-sensitized animal.(5)
Nowadays, Angiotensin Convertase Inhibitors (ACEIs) are important drugs in the treatment of high blood pressure, heart failure and some nephropathic disorders, but one of the most common side effects of these drugs is cough: a dry cough, together with itching, which is usually disturbing, affecting around 15 to 39 percent of these patients, which may result in termination of the treatment. In a placebo-controlled, double-blind clinical trial, 60 patients with hypertension and cough induced by the use of ACEIs, were treated with marshmallow or placebo for 4 weeks. The results showed that marshmallow has important effects in the reduction and healing of cough induced by ACEIs.(6)
3- Common Ivy: Among the non-antibiotic drugs for cough, herbal medicines containing common ivy with the scientific name Hedera helix are quite well-known. In a systematic survey to evaluate the efficacy and tolerance of common ivy in cases of Acute Upper Respiratory Tract Infections (URTI), the results of 10 clinical studies (common ivy alone, or common ivy and thyme) showed that the extract of common ivy leaves is effective in reducing the symptoms of URTI and the combination of common ivy and thyme might have a better efficacy.(7)
Dry extract of common ivy leaves has been registered as an expectorant medicine in patients with respiratory disorders with productive cough. Apart from secretolytic properties, bronchial spasmolytic properties have also been mentioned. In a double-blind, placebo-controlled, randomized, crossover clinical study, 30 children between 9-11 with partial allergic asthma or uncontrolled (despite long treatment with an equivalent of 400 µg budesonide), persistent, mild asthma were studied. After a 4-week run-in period, the patients received either common ivy leaf dry extract together with inhaled corticosteroid or placebo. Before the alteration in the treatment, there was a wash-out period. Lung function, Fractional exhaled Nitric Oxide (FeNO) levels, the pH of the compressed exhalation air, and quality of life were analyzed after each phase of the treatment. After the treatment with common ivy leaf dry extract there was significant improvement in MEF75-25 and MEF25 and Vital Capacity (VC); there was no such improvement with placebo. This study showed that children with non-controlled mild asthma despite regular treatment with inhaled corticosteroid, may benefit from adjuvant therapy with common ivy leaves.(8)
4- Shirazi Thyme, Marshmallow and Common Ivy: In a randomized, double-blind clinical trial, 188 patients with acute cough received either Coughnolix Syrup containing Shirazi thyme, marshmallow and common ivy (93 patients) or Dextromethorphan syrup (95 patients) with the amount of 5 ml every 8 hours for 4 days. The patients were visited in person in the beginning and at the end of the intervention and via phone in 24 and 48 hour intervals, and the findings were registered in questionnaires. The intensity of the coughs was registered using VAS index on a line bar from 0 to 10 (0: no cough, 10: debilitating cough) by the patients. In every evaluation, the improvement level was registered as total recovery (total cessation of cough), relative recovery (satisfaction of the patient with reduction in cough or reduction of the duration of cough to half) or no improvement (no change in cough intensity). Based on the results of this study, the score of cough intensity at the beginning of the study, 24, 48 and 96 hours after the beginning of the study was 5.53, 4.78, 3.07 and 1.25 in the dextromethorphan group, respectively, and 6.04, 4.57, 2.53 and 0.54 in the Coughnolix group, respectively; statistically significant reduction in the intensity of the cough was observed in both groups in all stages (p>0.001). Also, after 96 hours of treatment, the rate of total recovery was 39.4 percent in the Dextromethorphan group and 61.7 percent in the Coughnolix group and the difference between the two groups was statistically significant (p=0.008). The researchers concluded that the syrup containing Shirazi thyme, marshmallow and common ivy, with an efficacy equal to, or more than, dextropethorphan, can be a good alternative in treatment of cough.