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Myrtol activates fluid secretion in sinonasal epithelial cells. (A and B) Confocal Z-section images of Texas red dextran-labeled airway surface liquid (ASL) from (A) 0.5% ethanol and (B) Myrtol-stimulated (45 minutes) air-liquid interfaces (ALIs; n 3 each). (C) Graph of mean ASL heights SEM.
Source publication
Background:
Herbal remedies predate written history and continue to be used frequently for many common ailments. The essential oil mixture standardized is a phytopharmaceutical with a distillate of a mixture of rectified essential oils of eucalyptus, sweet orange, myrtle, and lemon as active ingredients used to treat respiratory diseases such as b...
Contexts in source publication
Context 1
... confirm that the SPQ results reflected Myrtol activating epithe- lial fluid secretion, we directly measured sinonasal ALIs fluid secre- tion using techniques previously developed to measure ASL homeo- stasis. 19 ASL was stained with Texas red dextran before depth measurement via confocal imaging; a decrease in ASL height reflects a decrease in fluid volume whereas an increase in ASL height reflects an increase in fluid volume. Resting ASL height in human sinonasal ALIs was 11 2 m (Fig. 6 A). Cultures exposed to basolateral Myrtol exhibited significantly higher ASL after 45 minutes (24 3 m; ...
Context 2
... hydration is paramount for normal MCC. In addition to stimulating CBF we show in the human sinonasal ALI model that Myrtol is a potent stimulant of respiratory epithelial fluid secretion as evident by the increase in ASL height (Fig. 6). We further show that this hydration is most likely caused by chloride efflux (Fig. 5). How- ever, the exact target of Myrtol is still unknown. As was evident in the CBF experiments, only basolateral application of Myrtol altered chlo- ride permeability, suggesting that the target may be found on the basolateral membrane. It is important to note that the dual effect of Myrtol on fluid secretion and CBF yields a synergistic effect on mucociliary transport. Although 0.5% Myrtol yielded robust changes in CBF (Fig. 1) and ASL height (Fig. 6), 0.1% resulted in dramatic changes in mucus transport velocity (Fig. ...
Context 3
... hydration is paramount for normal MCC. In addition to stimulating CBF we show in the human sinonasal ALI model that Myrtol is a potent stimulant of respiratory epithelial fluid secretion as evident by the increase in ASL height (Fig. 6). We further show that this hydration is most likely caused by chloride efflux (Fig. 5). How- ever, the exact target of Myrtol is still unknown. As was evident in the CBF experiments, only basolateral application of Myrtol altered chlo- ride permeability, suggesting that the target may be found on the basolateral membrane. It is important to note that the dual effect of Myrtol on fluid secretion and CBF yields a synergistic effect on mucociliary transport. Although 0.5% Myrtol yielded robust changes in CBF (Fig. 1) and ASL height (Fig. 6), 0.1% resulted in dramatic changes in mucus transport velocity (Fig. ...
Context 4
... tion using techniques previously developed to measure ASL homeo- stasis. 19 ASL was stained with Texas red dextran before depth measurement via confocal imaging; a decrease in ASL height reflects a decrease in fluid volume whereas an increase in ASL height reflects an increase in fluid volume. Resting ASL height in human sinonasal ALIs was 11 2 m (Fig. 6 A). Cultures exposed to basolateral Myrtol exhibited significantly higher ASL after 45 minutes (24 3 m; ...
Context 5
... hydration is paramount for normal MCC. In addition to stimulating CBF we show in the human sinonasal ALI model that Myrtol is a potent stimulant of respiratory epithelial fluid secretion as evident by the increase in ASL height (Fig. 6). We further show that this hydration is most likely caused by chloride efflux (Fig. 5). How- ever, the exact target of Myrtol is still unknown. As was evident in the CBF experiments, only basolateral application of Myrtol altered chlo- ride permeability, suggesting that the target may be found on the basolateral membrane. It is ...
Context 6
... basolateral application of Myrtol altered chlo- ride permeability, suggesting that the target may be found on the basolateral membrane. It is important to note that the dual effect of Myrtol on fluid secretion and CBF yields a synergistic effect on mucociliary transport. Although 0.5% Myrtol yielded robust changes in CBF (Fig. 1) and ASL height (Fig. 6), 0.1% resulted in dramatic changes in mucus transport velocity (Fig. ...
Citations
... В результате такой комбинации скорость выведения слизи из дыхательных путей повышается на 46%, прирост секретолиза составляет 32%. Кроме того, вышеназванные препараты обладают противовоспалительным и антибактериальным свой ст вами [7][8][9][10][11]. Противовоспалительный эффект способствует снижению отека дыхательных путей, в то время как антимикробные компоненты препятствуют активизации бактериальных возбудителей болезни, что чрезвычайно важно для предотвращения бактериальной колонизации и клинической манифестации бактериальной инфекции. ...
Introduction . Acute respiratory viral infections are the most widespread diseases, accounting for up to 90% of all infectious pathology, which supports the relevance of optimizing the treatment of acute viral rhinosinusitis. Aim . Evaluate the dynamics of clinical symptoms of acute viral rhinosinusitis, which arose as part of an acute respiratory infection, when supplementing therapy with the drug Respero Myrtol (Pol-Boskamp GmbH and Co.KG, Germany), the active ingredient of which is myrtol standardized 120 mg in 1 capsule. Materials and methods. The dynamics of clinical symptoms of 20 cases of acute viral rhinosinusitis in comparison groups was analyzed. Traditional treatment of patients included taking propionic acid derivatives, ascorbic acid, intranasal use of decongestants and irrigation of the nasal cavity with isotonic saline solutions. Patients who have received traditional treatment are defined as a “standard therapy group”. To assess the effectiveness of therapy using standardized myrtol, 20 cases of acute viral rhinosinusitis against the background of acute respiratory viral infections with a similar severity were analyzed, in which patients received outpatient therapy with Respero Myrtol 2 capsules 3 times a day for 7 days in addition to the above treatment (the “myrtol therapy” group). The dynamics of the disease assessed: the number of days of disability before recovery, the period of normalization of body temperature in feverish patients, the need for vasoconstrictive intranasal agents after the seventh day of therapy, the period of complete relief of pain syndrome, the period of normalization of night sleep, the number of cases of bacterial superinfection and the need for systemic antibacterial therapy. The results . In the observed patients, the quality of sleep was restored faster, the pain syndrome was stopped earlier, less often there was a need for systemic antibiotics and prolonged use of intranasal decongestants. The disease proceeded with fewer days of disability. Conclusion . The study results have been shown to report the clinical efficacy of Respero Myrtol essential oils in the outpatient treatment of patients with acute rhinosinusitis.
... Eucalyptus oil, thyme oil and menthol, when delivered nasally has been shown to increase ciliary beat frequency which has the benefit of improving mucociliary clearance [133]. Similarly, Myrtol ® a mixture of aromatic essential oils, including eucalyptus oil, which is taken orally for respiratory disorders, showed evidence of improving mucociliary clearance and increased ciliary beat frequency both in vitro and ex vivo [134]. Thymol also plays a role in increasing mucociliary clearance [128] and has been shown to have anti-inflammatory effects in allergic disorders of the respiratory system [135]. ...
Background
Upper respiratory tract infections (URTIs) impact all age groups and have a significant economic and social burden on society, worldwide. Most URTIs are mild and self-limiting, but due to the wide range of possible causative agents, including Rhinovirus (hRV), Adenovirus, Respiratory Syncytial Virus (RSV), Coronavirus and Influenza, there is no single and effective treatment. Over-the-counter (OTC) remedies, including traditional medicines and those containing plant derived substances, help to alleviate symptoms including inflammation, pain, fever and cough.
Purpose
This systematic review focuses on the role of the major plant derived substances in several OTC remedies used to treat cold symptoms, with a particular focus on the transient receptor potential (TRP) channels involved in pain and cough.
Methods
Literature searches were done using Pubmed and Web of Science, with no date limitations, using the principles of the PRISMA statement. The search terms used were ‘TRP channel AND plant compound’, ‘cough AND plant compound’, ‘cough AND TRP channels AND plant compound’, ‘cough AND P2X3 AND plant compound’ and ‘P2X3 AND plant compound’ where plant compound represents menthol or camphor or eucalyptus or turpentine or thymol.
Results
The literature reviewed showed that menthol activates TRPM8 and may inhibit respiratory reflexes reducing irritation and cough. Menthol has a bimodal action on TRPA1, but inhibition may have an analgesic effect. Eucalyptus also activates TRPM8 and inhibits TRPA1 whilst down regulating P2X3, aiding in the reduction of cough, pain and airway irritation. Camphor inhibits TRPA1 and the activation of TRPM8 may add to the effects of menthol. Activation of TRPV1 by camphor, may also have an analgesic effect.
Conclusions
The literature suggests that these plant derived substances have multifaceted actions and can interact with the TRP ‘cough’ receptors. The plant derived substances used in cough and cold medicines have the potential to target multiple symptoms experienced during a cold.
... Experiments utilized Dulbecco's PBS (+ 1.8 mM Ca 2+ ) on the apical side and 20 mM HEPES-buffered Hank's Balanced Salt Solution supplemented with 1× MEM vitamins and amino acids on the basolateral side. Data were analyzed using the Sisson-Ammons Video Analysis system and normalized to baseline CBF as previously described (4,22,(79)(80)(81)(82). ...
Introduction
Bitter taste receptors (T2Rs) are G protein-coupled receptors identified on the tongue but expressed all over the body, including in airway cilia and macrophages, where T2Rs serve an immune role. T2R isoforms detect bitter metabolites (quinolones and acyl-homoserine lactones) secreted by gram negative bacteria, including Pseudomonas aeruginosa , a major pathogen in cystic fibrosis (CF). T2R activation by bitter bacterial products triggers calcium-dependent nitric oxide (NO) production. In airway cells, the NO increases mucociliary clearance and has direct antibacterial properties. In macrophages, the same pathway enhances phagocytosis. Because prior studies linked CF with reduced NO, we hypothesized that CF cells may have reduced T2R/NO responses, possibly contributing to reduced innate immunity in CF.
Methods
Immunofluorescence, qPCR, and live cell imaging were used to measure T2R localization, calcium and NO signaling, ciliary beating, and antimicrobial responses in air-liquid interface cultures of primary human nasal epithelial cells and immortalized bronchial cell lines. Immunofluorescence and live cell imaging was used to measure T2R signaling and phagocytosis in primary human monocyte-derived macrophages.
Results
Primary nasal epithelial cells from both CF and non-CF patients exhibited similar T2R expression, localization, and calcium signals. However, CF cells exhibited reduced NO production also observed in immortalized CFBE41o- CF cells and non-CF 16HBE cells CRISPR modified with CF-causing mutations in the CF transmembrane conductance regulator (CFTR). NO was restored by VX-770/VX-809 corrector/potentiator pre-treatment, suggesting reduced NO in CF cells is due to loss of CFTR function. In nasal cells, reduced NO correlated with reduced ciliary and antibacterial responses. In primary human macrophages, inhibition of CFTR reduced NO production and phagocytosis during T2R stimulation.
Conclusions
Together, these data suggest an intrinsic deficiency in T2R/NO signaling caused by loss of CFTR function that may contribute to intrinsic susceptibilities of CF patients to P. aeruginosa and other gram-negative bacteria that activate T2Rs.
... Experiments utilized Dulbecco's PBS (+ 1.8 mM Ca 2+ ) on the apical side and 20 mM HEPES-buffered Hank's Balanced Salt Solution supplemented with 1× MEM vitamins and amino acids on the basolateral side. Data were analyzed using the Sisson-Ammons Video Analysis system and normalized to baseline CBF as previously described (4,39,(74)(75)(76)(77). ...
Bitter taste receptors (T2Rs) are G protein-coupled receptors identified on the tongue but expressed all over the body, including in airway cilia and macrophages, where T2Rs serve an immune role. T2R isoforms detect bitter metabolites (quinolones and acyl-homoserine lactones) secreted by gram negative bacteria, including Pseudomonas aeruginosa, a major pathogen in cystic fibrosis (CF). T2R activation by bitter bacterial products triggers calcium-dependent nitric oxide (NO) production. In airway cells, the NO increases mucociliary clearance and has direct antibacterial properties. In macrophages, the same pathway enhances phagocytosis. Because prior studies linked CF with reduced NO, we hypothesized that CF cells may have reduced T2R/NO responses. Using qPCR, immunofluorescence, and live cell imaging of air-liquid interface cultures, we found primary nasal epithelial cells from both CF and non-CF patients exhibited similar T2R expression, localization, and calcium signals. However, CF cells exhibited reduced NO production also observed in immortalized CFBE41o- CF cells and non-CF 16HBE cells CRISPR modified with CF-causing mutations in the CF transmembrane conductance regulator (CFTR). NO was restored by VX-770/VX-809 corrector/potentiator pre-treatment, suggesting reduced NO in CF cells is due to loss of CFTR function. In nasal cells, reduced NO correlated with reduced ciliary and antibacterial responses. In primary human macrophages, inhibition of CFTR reduced NO production and phagocytosis during T2R stimulation. Together, these data suggest an intrinsic deficiency in T2R/NO signaling caused by loss of CFTR function that may contribute to intrinsic susceptibilities of CF patients to P. aeruginosa and other gram-negative bacteria that activate this pathway.
... The last two symptoms might at least partially be due to the loss of ciliary function during infection and the resulting impairment of MCC [1]. Drug substances that modulate ciliary beat frequency and/or enhance the mucociliary escalator might therefore be reasonable treatment options [5,6]. ...
... ELOM-080 is a phytomedicine that has mucolytic, secretolytic, secretomotoric, anti-inflammatory, antioxidant, antimicrobial and bronchospasmolytic effects [6][7][8], and has demonstrated clinical efficacy, safety and tolerability in clinical trials [9][10][11][12]. ...
... ELOM-080 is a potent enhancer of MCC [5,6], and the findings of the current study support this mode of action, because of its beneficial effects on the passage for ventilation in the conducting zone. Additionally, ELOM-080 supports differentiation of ciliary epithelium in vitro and thereby may facilitate recovery of impaired MCC following viral infection [1,18]. ...
Introduction:
Enhancement of mucociliary clearance (MCC) might be a potential target in treating COVID-19. The phytomedicine ELOM-080 is an MCC enhancer that is used to treat inflammatory respiratory diseases.
Patients/methods:
This randomised, double-blind exploratory study (EudraCT number 2020-003779-17) evaluated 14 days' add-on therapy with ELOM-080 versus placebo in patients with COVID-19 hospitalised with acute respiratory insufficiency.
Results:
The trial was terminated early after enrolment of 47 patients as a result of poor recruitment. Twelve patients discontinued prematurely, leaving 35 in the per-protocol set (PPS). Treatment with ELOM-080 had no significant effect on overall clinical status versus placebo (p = 0.49). However, compared with the placebo group, patients treated with ELOM-080 had less dyspnoea in the second week of hospitalisation (p = 0.0035), required less supplemental oxygen (p = 0.0229), and were more often without dyspnoea when climbing stairs at home (p < 0.0001).
Conclusion:
These exploratory data suggest the potential for ELOM-080 to improve respiratory status during and after hospitalisation in patients with COVID-19.
... Administration of nebulized CBF inhibitors and enhancers quantifiably decreased or increased mucociliary clearance, respectively Boek et al. (1999); Boek et al. (2002). Increased CBF and MCT was also noted in human sinonasal epithelial cell cultures treated with Myrtol ® , an essential oil distillate Lai et al. (2014) Serous and glandular secretions of the airway epithelium contribute to the ASL, and epithelial ion channel function is critical to ASL homeostasis. Absorption of liquid to and from the mucus layer serves to maintain ASL depth. ...
Adverse outcome pathways (AOPs) help to organize available mechanistic information related to an adverse outcome into key events (KEs) spanning all organizational levels of a biological system(s). AOPs, therefore, aid in the biological understanding of a particular pathogenesis and also help with linking exposures to eventual toxic effects. In the regulatory context, knowledge of disease mechanisms can help design testing strategies using in vitro methods that can measure or predict KEs relevant to the biological effect of interest. The AOP described here evaluates the major processes known to be involved in regulating efficient mucociliary clearance (MCC) following exposures causing oxidative stress. MCC is a key aspect of the innate immune defense against airborne pathogens and inhaled chemicals and is governed by the concerted action of its functional components, the cilia and airway surface liquid (ASL). The AOP network described here consists of sequences of KEs that culminate in the modulation of ciliary beat frequency and ASL height as well as mucus viscosity and hence, impairment of MCC, which in turn leads to decreased lung function.
... Whole-field CBF was measured using the Sisson-Ammons Video Analysis system (73) as previously described (18,74,75) (74)(75)(76)(77), changes in CBF were normalized to baseline CBF. This was validated by measurements of raw baseline CBF (in Hz) between control and experimental cultures, as indicated in the text. ...
Bitter taste receptors (T2Rs) are G protein-coupled receptors (GPCRs) expressed in various cell types including ciliated airway epithelial cells and macrophages. T2Rs in these two airway innate immune cell types are activated by bitter products, including those secreted by common airway pathogens like Pseudomonas aeruginosa, leading to Ca2+-dependent activation of endothelial nitric oxide (NO) synthase (eNOS). NO production leads to enhanced mucociliary clearance and direct antibacterial effects by ciliated epithelial cells as well as increased phagocytosis by macrophages. Using biochemistry and live cell imaging, we explored the role of heat shock protein 90 (HSP90) in regulating T2R-dependent NO pathways in primary sinonasal epithelial cells, primary monocyte-derived macrophages, and a human bronchiolar cell line (H441). We used immunofluorescence to show that H441 cells express eNOS and certain T2Rs and that the bitterant denatonium benzoate activates NO production in an HSP90-dependent manner in cells grown either as submerged cultures and at air liquid interface. In primary sinonasal epithelial cells, we determined that HSP-90 inhibition reduces T2R-stimulated NO production and ciliary beating which are crucial for pathogen clearance. In primary monocyte-derived macrophages, we found that HSP-90 is integral to T2R-stimulated NO production and phagocytosis of FITC-labeled Escherichia coli and pHrodo-Staphylococcus aureus. Our study demonstrates that HSP90 serves an innate immune role by regulating NO production downstream of T2R signaling by augmenting eNOS activation without impairing upstream calcium signaling. These findings suggest that HSP90 plays an important role in airway antibacterial innate immunity and may be an important target in airway diseases like chronic rhinosinusitis, asthma, or cystic fibrosis.
... В результате такой комбинации скорость выведения слизи из дыхательных путей повышается на 46%, прирост секретолиза составляет 32%. Кроме того, вышеназванные препараты обладают противовоспалительным и антибактериальным свойствами [12][13][14]. Противовоспалительный эффект способствует снижению отека дыхательных путей, в то время как антимикробные компоненты активно борются с возбудителями болезни, что чрезвычайно важно для предотвращения бактериальной инфекции и колонизации. Противовоспалительное и антиоксидантное действие Миртола стандартизированного обусловлено нейтрализацией активных форм кислорода, подавлением синтеза этилена и снижением уровня гистамина [15,16]. ...
... Высвобождение активного вещества в кишечнике значительно увеличивает его биодоступность, приближая ее к 100% [18]. Действующие вещества препаратов ГелоМиртол® и ГелоМиртол® форте проникают в кровоток и распространяются по всему организму, быстро достигая структур респираторного тракта, где оказывают свое лечебное воздействие [12][13][14]. ...
Respiratory diseases are a widespread group of pathological processes that affect people of different ages. Inflammatory changes of various etiologies on the surface of the respiratory epithelium are accompanied by a violation of mucociliary clearance, and therefore the rate of evacuation of the secret decreases, its production increases, and the rheological properties of the mucin change. Significant accumulation of thick mucus is a clinical feature of many respiratory diseases, including acute rhinosinusitis. Appointment to patients with pathology of the respiratory system of drugs that affect the evacuation, properties and production of mucus, is pathogenetically justified. Phytopreparations GeloMirtol® and GeloMirtol® forte are effective in treating patients with rhinosinusitis of various ages, including children from 6 and 10, respectively. The active component of these drugs - Myrtle standardized - distillate eucalyptus oil (main ingredient - 66% of the total), myrtle, sweet orange and lemon, has a complex mechanism of action, has an expectorant, anti-inflammatory, bacteriostatic effect, helps clean the respiratory tract and restore normal mucous function shell. GeloMirtol® and GeloMirtol® forte simultaneously affect several parts of the development of the pathological process, increasing the results of complex treatment of respiratory diseases.
... Additionally, essential oils (eg, eucalyptus) have antibacterial, antifungal, and antiviral activity. [19][20][21] Menthol has been used for many years as a traditional medicine in Asia. It is a natural herbal compound. ...
The purpose of the study was to compare treatment of chronic rhinosinusitis (CRS) with topical glucocorticoids and saline irrigation versus aerosol inhalation therapy. Patients diagnosed with CRS were randomly divided into 2 groups. In the first group, patients were treated with topical glucocorticoids (mometasone furoate, 100 μg in each nostril once daily) and saline irrigation (150 mL twice a day) for 2 weeks. In the second group, patients were treated with inhalation aerosol therapy composed of essential oils, saline, glucocorticoids, and antibiotics, once daily 5 times per week (Monday through Friday), for 2 weeks. The effect of the treatments was compared between the 2 groups. In the first group there was no significant improvement in the Glasgow Health Status Inventory (GHSI) (P = .29). In the second group the improvement in GHSI score was significant (P = .037). It was shown that in the first group the Glasgow Benefit Inventory score was significantly lower than in the second group (P = .002), which means that the improvement in the health status after the therapy was better in the second group. A Lund‐Kennedy score showed statistical improvement in both groups (both P < .001). Improvement was also compared between the groups. The results were not significant (P = .11). The authors concluded that, in this preliminary research, inhalation aerosol therapy composed of essential oils, saline, glucocorticoids, and antibiotics led to better subjective results than intranasal glucocorticoid therapy and saline irrigation in the treatment of CRS. Further investigations with more participants, longer periods of treatment, and different validation tools are needed to confirm our results.
... Articles in Chinese language (in particular all included 25 studies) were translated into English by a native speaker, Betty Luong, from the Institute of Pharmaceutical Biology, Goethe University, Frankfurt, Germany. Of note, none of the clinical trials and with one exception [25] none of the experimental studies on mucociliary clearance were sponsored by the pharmaceutical manufacturer of ELOM-080. The trials were initiated, financed, and conducted solely by the respective Chinese investigators. ...
... The influence of ELOM-080 on mucociliary clearance in vivo was at first demonstrated in a pilot study by German researchers [9] and has been recently updated in vitro by another research group [7]. Interestingly, it is the great merit of several Chinese research groups to provide an in depth understanding of the mode of action and to characterize ELOM-080 as an enhancer of the mucociliary clearance [25,[55][56][57]. These Chinese research groups investigated the mode of action of ELOM-080 using different in vitro techniques. ...
... ELOM-080 (250 ng/mL) was found to increase the ciliary beat frequency (CBF) of nasal epithelial cells isolated from healthy subjects, COPD patients, and bronchiectasis patients after 4 h of incubation at 37°C [57]. A more detailed study revealed that ELOM-080 only effects CBF and chloride secretion when it is applied from the basolateral site and also observed a concentration-dependent effect taking into account that the applied concentrations were significantly higher compared to the previous studies [25]. With reference to the basolateral site instead of apical applications, it is necessary to emphasize that in clinical settings the basolateral pathway is clinically more relevant, because it mirrors the hematogenic distribution of ELOM-080 [55]. ...
ELOM-080, also known as Myrtol, represents a distillate of a mixture of 4 rectified essential oils: eucalyptus oil, sweet orange oil, myrtle oil, and lemon oil. ELOM-080 is an approved herbal medicinal product for the secretolytic therapy and facilitation of expectoration in acute and chronic bronchitis and for the secretolytic therapy of sinusitis. Its clinical efficacy has been reported by several randomized control trials. Interestingly, in the recent past, a considerable number of clinical studies on the use of ELOM-080 as add-on treatment of different respiratory tract diseases has been conducted and published in China. As these publications were only available in Chinese, the international attention in the literature was limited. Based on the translation of these studies into English, this review aims to provide a brief overview of the studies' major results, which contribute to the knowledge on the efficacy of ELOM-080 in the treatment of respiratory tract diseases: ELOM-080 was shown to be of great value as add-on treatment not only for the well-established indications bronchitis and sinusitis, but also for pharyngitis, asthma, chronic obstructive pulmonary disease, and, most importantly, otitis media. Besides this clinical evidence, this review also summarizes the great progress in deciphering the mode of action of ELOM-080 that has been made by Chinese publications.
