Ambroxol Research Articles

Evaluating the mucolytic effectiveness of Ambroxol and N-Acetylcysteine in patients with Acute exacerbation of chronic obstructive pulmonary disease

IntroductionChronic obstructive pulmonary disease (COPD) is the third most fatal disease globally. Acute deterioration of the patient's respiratory symptoms is known as an acute exacerbation of COPD (AECOPD), that goes beyond usual variations and result in change in medications. Ambroxol (ABX) and N-acetylcysteine (NAC), are mainly used as mucolytics in the treatment of AECOPD. MethodologyThis prospective observational study examines effectiveness of ABX and NAC in COPD patients by assessing the quality of cough relief, peak expiratory flow rate (PEFR), length of hospital stay, quality of life (QOL) and reduction in symptoms of COPD. Leicester Cough Questionnaire (LCQ); Breathlessness, Cough and Sputum scale (BCSS)and St. George Respiratory Questionnaire (SGRQ) scales are used to evaluate patient condition before and after the treatment. ResultsThe mean duration of hospital stay for NAC and ABX were found to be 8 ± 3.6 and 9.9 ± 3.9 days, respectively. Lung function in both groups improved with a change in percentage mean score of PEFR. Reduction in symptoms of COPD was evident in both groups by decrease in mean BCSS score from admission to discharge. Our study also demonstrated better QOL in both groups using SGRQ. LCQ showed a mean increase in all domains: physical, psychological and social. ConclusionIt was concluded that both ABX and NAC leads to betterment in lung function, cough relief and control AECOPD. Hence, this study gives a signal to clinicians about these treatment options along with standard therapy of COPD for a better therapeutic outcome.

Exploring the efficacy and safety of Ambroxol in Gaucher disease: an overview of clinical studies.

Gaucher disease (GD) is mainly caused by glucocerebrosidase (GCase) enzyme deficiency due to genetic variations in the GBA1 gene leading to the toxic accumulation of sphingolipids in various organs, which causes symptoms such as anemia, thrombocytopenia, hepatosplenomegaly, and neurological manifestations. GD is clinically classified into the non-neuronopathic type 1, and the acute and chronic neuronopathic forms, types 2 and 3, respectively. In addition to the current approved GD medications, the repurposing of Ambroxol (ABX) has emerged as a prospective enzyme enhancement therapy option showing its potential to enhance mutated GCase activity and reduce glucosylceramide accumulation in GD-affected tissues of different GBA1 genotypes. The variability in response to ABX varies across different variants, highlighting the diversity in patients' therapeutic outcomes. Its oral availability and safety profile make it an attractive option, particularly for patients with neurological manifestations. Clinical trials are essential to explore further ABX's potential as a therapeutic medication for GD to encourage pharmaceutical companies' investment in its development. This review highlights the potential of ABX as a pharmacological chaperone therapy for GD and stresses the importance of addressing response variability in clinical studies to improve the management of this rare and complex disorder.

Ambroxol-Enhanced Frequency and Amplitude of Beating Cilia Controlled by a Voltage-Gated Ca2+ Channel, Cav1.2, via pHi Increase and [Cl-]i Decrease in the Lung Airway Epithelial Cells of Mice.

Ambroxol (ABX), a frequently prescribed secretolytic agent which enhances the ciliary beat frequency (CBF) and ciliary bend angle (CBA, an index of amplitude) by 30%, activates a voltage-dependent Ca2+ channel (CaV1.2) and a small transient Ca2+ release in the ciliated lung airway epithelial cells (c-LAECs) of mice. The activation of CaV1.2 alone enhanced the CBF and CBA by 20%, mediated by a pHi increasei and a [Cl-]i decrease in the c-LAECs. The increase in pHi, which was induced by the activation of the Na+-HCO3- cotransporter (NBC), enhanced the CBF (by 30%) and CBA (by 15-20%), and a decrease in [Cl-]i, which was induced by the Cl- release via anoctamine 1 (ANO1), enhanced the CBA (by 10-15%). While a Ca2+-free solution or nifedipine (an inhibitor of CaV1.2) inhibited 70% of the CBF and CBA enhancement using ABX, CaV1.2 enhanced most of the CBF and CBA increases using ABX. The activation of the CaV1.2 existing in the cilia stimulates the NBC to increase pHi and ANO1 to decrease the [Cl-]i in the c-LAECs. In conclusion, the pHi increase and the [Cl-]i decrease enhanced the CBF and CBA in the ABX-stimulated c-LAECs.

Ambroxol as a disease-modifying treatment to reduce the risk of cognitive impairment in GBA-associated Parkinson’s disease: a multicentre, randomised, double-blind, placebo-controlled, phase II trial. The AMBITIOUS study protocol

BackgroundHeterozygous mutations in the GBA gene, encoding the lysosomal enzyme β-glucocerebrosidase (GCase), are the most frequent genetic risk factor for Parkinson’s disease (PD). GBA-related PD (GBA-PD) patients have higher risk...

The ANeED study - ambroxol in new and early dementia with Lewy bodies (DLB): protocol for a phase IIa multicentre, randomised, double-blinded and placebo-controlled trial.

Currently, there are no disease-modifying pharmacological treatment options for dementia with Lewy bodies (DLB). The hallmark of DLB is pathological alpha-synuclein (aS) deposition. There are growing amounts of data suggesting that reduced aS clearance is caused by failure in endolysosomal and authophagic pathways, as well as and glucocerebrosidase (GCase) dysfunction and mutations in the GCase gene (GBA). The population's studies demonstrated that the incidence of GBA mutations is higher among Parkinson's disease (PD) patients, and carriers of such mutations have a higher risk of developing PD. The incidence of GBA mutations is even higher in DLB and a genome-wide association study (GWAS) confirmed the correlation between GBA mutations and DLB. In vivo experiments have shown that ambroxol (ABX) may increase GCase activity and GCase levels and therefore enhance aS autophagy-lysosome degradation pathways. Moreover, there is an emerging hypothesis that ABX may have an effect as a DLB modifying drug. The aims of the study "Ambroxol in new and early Dementia with Lewy Bodies (ANeED) are to investigate the tolerability, safety and effects of ABX in patients with DLB. This is a multicentre, phase IIa, double-blinded, randomised and placebo-controlled clinical trial, using a parallel arm design for 18 months' follow-up. The allocation ratio is 1:1 (treatment:placebo). The ANeED study is an ongoing clinical drug trial with ABX. The unique, but not fully understood mechanism of ABX on the enhancement of lysosomal aS clearance may be promising as a possible modifying treatment in DLB. The clinical trial is registered in the international trials register - clinicaltrials.com (NCT0458825) and nationally at the Current Research Information System in Norway (CRISTIN 2235504).

Ambroxol-enhanced ciliary beating via voltage-gated Ca2+ channels in mouse airway ciliated cells

Ambroxol (ABX) facilitates the mucociliary clearance (MC) by enhancing ciliary beating in airways. In this study, we focused on airway ciliary beating enhanced by ABX. However, little is known about the ABX-stimulated Ca2+ signalling activating airway ciliary beating. Airway ciliated cells isolated from mice lungs were observed by a high-speed video microscope, and the activities of beating cilia were assessed by CBF (ciliary beat frequency) and CBD (ciliary bend distance, an index of amplitude). ABX (10 μM) enhanced the CBF and CBD by 30%, and the enhancement was inhibited by nifedipine (20 μM, a L-type voltage-gated Ca2+ channel (CaV) inhibitor), or a Ca2+-free solution (approximately 50%). Pre-treatment with BAPTA-AM (10 μM, a chelator of intracellular Ca2+) abolished ABX-stimulated increases in CBF, CBD and [Ca2+]i. Thus, ABX increases [Ca2+]i (intracellular Ca2+ concentration) by stimulating Ca2+ release from the internal stores and nifedipine-sensitive Ca2+ entry. A previous study demonstrated the expression of CaV1.2 in airway cilia. ABX enhanced CBF, CBD and [Ca2+]i even in a high extracellular K+ concentration (155.5 mM), suggesting that it activates CaV1.2 except by depolarization. These enhancements were inhibited by nifedipine. In conclusion, ABX, which increases [Ca2+]i by stimulating Ca2+ release from internal stores and Ca2+ entry through CaV1.2s, enhanced CBF and CBD in airway ciliated cells. ABX is a novel agonist that modulates CaV1.2 of airway beating cilia to enhance CBF and CBD.

Comparison of Clinical Effectiveness Between Ambroxol and N-Acetylcysteine in Surgical Patients: A Retrospective Cohort Study.

Postoperative pulmonary complications (PPCs) are a major cause of postoperative morbidity, mortality, and longer hospital stays. Expectorants are widely used during the perioperative period to reduce PPCs. This study aimed to compare the clinical effectiveness between ambroxol (AMB) and N-acetylcysteine (NAC) in patients undergoing surgery. A multicenter, retrospective cohort study was conducted using deidentified medical records from hospital information system. Between July 1, 2015, and November 30, 2017, patients aged ≥18 years, who received intravenous AMB or nebulized NAC as the only expectorant therapy for >3days during their hospitalization for thoracic, abdominal, and neurosurgery, were included in this study. The clinical outcomes were evaluated, and propensity score matching was used to adjust significant differences between 2 groups. A total of 4025 cases in the AMB group and 2062 in NAC group after propensity score matching were identified. The incidence of PPCs (13.9% vs 11.6%; P=.013), postoperative sputum suction (17.2% vs 8.0%; P<.001), intensive care unit admission after surgery (25.1% vs 22.5%; P=.024), and postoperative mechanical ventilation (22.3% versus 17.5%; P<.001) in the AMB group were all significantly higher than those in the NAC group. This study suggested that patients treated with NAC during the perioperative period had a significantly lower risk of PPCs. However, further prospective study is needed to ensure the replicability of our findings.

Aquatic photolysis of the pharmaceutical ambroxol: The role of 2,4-dibromoaniline chromophore and heavy atom effect of bromine

As one of the most effective expectorant class drugs, ambroxol (AMB) has been frequently used to treat acute and chronic bronchitis. Extensive use and human excretion result in the widespread occurrence of AMB in wastewater. Herein, we reported the photolysis of AMB in aqueous solution upon 254 nm ultraviolet radiation (UV254). Spectroscopic characterization showed that 2,4-dibromoaniline (DBA) moiety is the core chromophore of AMB. Quantum yield of DBA changed little at pH 4.0 - 9.0; however, AMB showed higher quantum yield at pH > 8.0. Both DBA and AMB have high photoreactivity, which can be attributed to the “heavy atom” effect of bromine substituents. The photolysis of AMB occurred through photoreduction, photoionization, photonucleophilic substitution, side-chain cleavage, and coupling reactions. Both AMB and DBA underwent debromination with yields reaching 80% under 3200 mJ cm−2 UV fluence. Photo-debromination occurred preferentially at the para-position. The presence of natural organic matter inhibited the photodegradation, mainly due to the light-screening effect. The photolysis of AMB was slightly enhanced in the presence of NO3− likely due to radical-induced oxidation. Bioluminescence inhibition assay revealed that photoproducts were not toxic. The results show that UV254 radiation with fluences relevant to advanced oxidation processes was effective for the abatement of AMB in wastewater. However, UV254 treatment of wastewater containing higher concentrations (˃ μg L−1) of AMB should be done with caution because the released Br− can be converted to toxic brominated disinfection byproducts and bromate in subsequent oxidation process.

Antitussive, Expectorant, and Anti-inflammatory Effects of Mahwangyounpae-tang, a Polyherbal Formula in ICR Mice

Objectives: The antitussive, expectorant, and anti-inflammatory effects of Mahwangyounpae-tang (MHYPT) aqueous extracts were observed in appropriate animal models of various respiratory disorders.Methods: MHYPT aqueous extracts were orally administered once a day for 11 days at dose levels of 400, 200, and 100 mg/kg. The effect of MHYPT was determined by comparing its antitussive effect with theobromine (TB), its expectorant effect with ambroxol (AM), and its anti-inflammatory effect with dexamethasone (DEXA).Results: MHYPT aqueous extracts (400 mg/kg) showed favorable antitussive effects comparable to those of TB (50 mg/kg) in the NH&lt;sub&gt;4&lt;/sub&gt;OH-exposure coughing mouse model and expectorant effects comparable to those of AM (250 mg/kg) in the phenol red-secretion mouse model, but MHYPT (400 mg/kg) showed less anti-inflammatory activity compared to DEXA (1 mg/kg) in the xylene-induced acute inflammatory mouse ear model under the experimental conditions used.Conclusion: MHYPT aqueous extracts administered at dosage levels of 400, 200, and 100 mg/kg induced dose-dependent and favorable antitussive, expectorant, and anti-inflammatory activities that occurred by simultaneous modulation of the activity of mast cells and respiratory mucous production under the experimental conditions used in this study.

Mechanistic Insight into the Mode of Action of Acid β-Glucosidase Enhancer Ambroxol.

Ambroxol (ABX) is a mucolytic agent used for the treatment of respiratory diseases. Bioactivity has been demonstrated as an enhancement effect on lysosomal acid β-glucosidase (β-Glu) activity in Gaucher disease (GD). The positive effects observed have been attributed to a mechanism of action similar to pharmacological chaperones (PCs), but an exact mechanistic description is still pending. The current study uses cell culture and in vitro assays to study the effects of ABX on β-Glu activity, processing, and stability upon ligand binding. Structural analogues bromohexine, 4-hydroxybromohexine, and norbromohexine were screened for chaperone efficacy, and in silico docking was performed. The sugar mimetic isofagomine (IFG) strongly inhibits β-Glu, while ABX exerts its inhibitory effect in the micromolar range. In GD patient fibroblasts, IFG and ABX increase mutant β-Glu activity to identical levels. However, the characteristics of the banding patterns of Endoglycosidase-H (Endo-H)-digested enzyme and a substantially lower half-life of ABX-treated β-Glu suggest different intracellular processing. In line with this observation, IFG efficiently stabilizes recombinant β-Glu against thermal denaturation in vitro, whereas ABX exerts no significant effect. Additional β-Glu enzyme activity testing using Bromohexine (BHX) and two related structures unexpectedly revealed that ABX alone can refunctionalize β-Glu in cellula. Taken together, our data indicate that ABX has little in vitro ability to act as PC, so the mode of action requires further clarification.

Амброксол у комплексному лікуванні хворих із гострими респіраторними захворюваннями

У статті описано інноваційні дані щодо оптимізації патогенетичної терапії в пацієнтів із гострими респіраторними захворюваннями з проявами трахеїту, бронхіту, ускладненими пневмонією в дорослих. Описано етіологічну структуру гострих респіраторних захворювань та стійкість до антибактеріальних препаратів. Показана роль амброксолу гідрохлориду в комплексному лікуванні хворих із гострими респіраторними захворюваннями з різними ускладненнями з боку дихальної системи. Встановлено, що використання амброксолу гідрохлориду позитивно впливає на основний етіологічний процес, зменшує термін стаціонарної стадії лікування через швидке припинення бактеріальної екскреції в середньому на 3,8 ± 0,7 дня у 75 % пацієнтів (р = 0,001).

The impact of ambroxol on the anti-inflammatory effect of azithromycin in lung tissue

The aim of this study was to compare the effects of two different doses of ambroxol (AMB) co-administered with azithromycin (AZIT) on the concentrations of bronchoalveolar lavage fluid (BALF) cytokines and serum biochemical parameters in an lipopolysaccharide (LPS)-induced acute lung injury mouse model. A total of 78 male Swiss albino mice were used for this investigation. After six mice had been separated as the control group (0 hours), the remaining animals were divided into the following three equal groups: LPS, LPS+AZIT+AMB30 and LPS+AZIT+AMB70. LPS, AZIT and AMB were administered intraperitoneally. BALF and serum samples were collected before (0 hour) and after applications at 4, 8, 16 and 24 hours under general anaesthesia, and then all mice were euthanised by cervical dislocation. Concentrations of tumor necrosis factor (TNF)α, interleukin (IL)-6 and IL-10 in BALF and aspartate aminotransferase (AST), alkaline phosphatase (ALP), urea and creatinine concentrations in serum were determined. Elevated TNFα and IL-6 concentrations in the LPS group were prevented at 8 and 16 hours in LPS+AZIT+AMB30 group. In addition, both treatment groups inhibited elevated IL-6 concentrations in the LPS group at 16 hours. LPS+AZIT+AMB30 and LPS+AZIT+AMB70 increased IL-10 concentrations at 16 and 4 hours, respectively. LPS caused significant elevations in urea concentrations at all sampling times and statistical fluctuations in other parameters at different sampling times. The increased ALP concentration in LPS group decreased in the treatment groups at 8 hours. In conclusion, the combination of low-dose AMB and AZIT may achieve beneficial effects in pulmonary infections by influencing the cytokine network.

QUALITY BY DESIGN APPROACH TO DEVELOP STABILITY INDICATING REVERSED-PHASE HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY METHOD DEVELOPMENT FOR AMBROXOL

Objective: As per requisition of current regulatory requirements, simple, rapid and sensitive method by 33 factorial quality by design approach was established and validated for Ambroxol (AMB) by reversed-phase high-performance liquid chromatography (RP-HPLC). Methods: A simple RP-HPLC method has been developed and validated with different parameters such as linearity, precision, repeatability, limit of detection (LOD), limit of quantitation (LOQ), accuracy as per International Conference for Harmonisation guidelines (Q2R1). Statistical data analysis was done for data obtained from different aliquots Runs on Agilent Tech. Gradient System with Auto injector, ultraviolet (UV) diode-array detection and Gradient Detector. Results: Equipped with Reverse Phase (Agilent) C18 column (4.6 mm × 100 mm; 2.5 μm), a 20 μl injection loop and UV730D Absorbance detector at 244 nm wave length and running chemstation 10.1 software and drugs along with degradants were separated via Methanol: (0.1% orthophosphoric acid) Water (75:25) of pH 3 as mobile phase setting flow rate 0.7 ml/min at ambient temperature the retention time of AMB were found to be 4.85 min. The industrialized method was found linear over the concentration range of 10–50 μg/ml for AMB while the LOD and LOQ of AMB was found to be 0.5174–0.2739 μg/ml, analytical method that concluded. Conclusion: There are no interfering peaks underperformed degradation conditions. Therefore, a sensitive, robust, accurate, and stability indicating method was developed with high degree of practical utility.

Ambroxol Hydrochloride Loaded Gastro-Retentive Nanosuspension Gels Potentiate Anticancer Activity in Lung Cancer (A549) Cells

This study aimed to develop gastro-retentive sustained-release ambroxol (ABX) nanosuspensions utilizing ambroxol-kappa-carrageenan (ABX-CRGK) complexation formulations. The complex was characterized by differential scanning calorimetry, powder x-ray diffractometer, and scanning electron microscopy. The prepared co-precipitate complex was used for the development of the sustained-release formulation to overcome the high metabolic and poor solubility problems associated with ABX. Furthermore, the co-precipitate complex was formulated as a suspension in an aqueous floating gel-forming vehicle of sodium alginate with chitosan, which might be beneficial for targeting the stomach as a good absorption site for ABX. The suspension exhibited rapid floating gel behaviour for more than 8 h, thus confirming the gastro-retentive effects. Particle size analysis revealed that the optimum nanosuspension (ABX-NS) had a mean particle size of 332.3 nm. Afterward, the ABX released by the nanoparticles would be distributed to the pulmonary tissue as previously described. Based on extensive pulmonary distribution, the developed nanosuspension-released ABX nanoparticles showed significant cytotoxic enhancement compared to free ABX in A549 lung cancer cells. However, a significant loss of mitochondrial membrane potential (MMP) also occurred. The level of caspase-3 was the highest in the ABX-NS-released particle-treated samples, with a value of 416.6 ± 9.11 pg/mL. Meanwhile, the levels of nuclear factor kappa beta, interleukins 6 and 1 beta, and tumour necrosis alpha (NF-kB, IL-6, IL-1β, and TNF-α, respectively) were lower for ABX-NS compared to free ABX (p < 0.05). In caspase-3, Bax, and p53, levels significantly increased in the presence of ABX-NS compared to free ABX. Overall, ABX-NS produced an enhancement of the anticancer effects of ABX on the A549 cells, and the developed sustained-release gel was successful in providing a gastro-retentive effect.

Cellular and biochemical response to chaperone versus substrate reduction therapies in neuropathic Gaucher disease.

Gaucher disease (GD) is caused by deficiency of the lysosomal membrane enzyme glucocerebrosidase (GCase) and the subsequent accumulation of its substrate, glucosylceramide (GC). Mostly missense mutations of the glucocerebrosidase gene (GBA) cause GCase misfolding and inhibition of proper lysosomal trafficking. The accumulated GC leads to lysosomal dysfunction and impairs the autophagy pathway. GD types 2 and 3 (GD2-3), or the neuronopathic forms, affect not only the Central Nervous System (CNS) but also have severe systemic involvement and progressive bone disease. Enzyme replacement therapy (ERT) successfully treats the hematologic manifestations; however, due to the lack of equal distribution of the recombinant enzyme in different organs, it has no direct impact on the nervous system and has minimal effect on bone involvement. Small molecules have the potential for better tissue distribution. Ambroxol (AMB) is a pharmacologic chaperone that partially recovers the mutated GCase activity and crosses the blood-brain barrier. Eliglustat (EGT) works by inhibiting UDP-glucosylceramide synthase, an enzyme that catalyzes GC biosynthesis, reducing GC influx load into the lysosome. Substrate reduction therapy (SRT) using EGT is associated with improvement in GD bone marrow burden score and bone mineral density parallel with the improvement in hematological parameters. We assessed the effects of EGT and AMB on GCase activity and autophagy-lysosomal pathway (ALP) in primary cell lines derived from patients with GD2-3 and compared to cell lines from healthy controls. We found that EGT, same as AMB, enhanced GCase activity in control cells and that an individualized response, that varied with GBA mutations, was observed in cells from patients with GD2-3. EGT and AMB enhanced the formation of lysosomal/late endosomal compartments and improved autophagy, independent of GBA mutations. Both AMB and EGT increased mitochondrial mass and density in GD2-3 fibroblasts, suggesting enhancement of mitochondrial function by activating the mitochondrial membrane potential. These results demonstrate that EGT and AMB, with different molecular mechanisms of action, enhance GCase activity and improve autophagy-lysosome dynamics and mitochondrial functions.

High efficiency photocatalytic degradation of Ambroxol over Mn doped TiO2: Experimental designs, identification of transformation products, mineralization and mechanism.

Ambroxol (AMB) is a drug commonly used for chronic bronchitis prevention. Once released in surface water, this recalcitrant chemical becomes a hazardous pollutant. Here, we investigated the ability of 1% Mn-doped TiO2 (Mn-TiO2) to mineralize AMB by photocatalysis. We studied the morphology, and the physical and electrochemical properties of Mn-TiO2 using X-ray diffraction, Scanning electron microscopy, Transmission electron microscopy, X-ray fluorescence, BET method, UV-visible, and electrochemical study and optimized the AMB degrading experimental conditions through response surface methodology (RSM). Mn-TiO2 at the dose of 0.625g·L-1 allowed the complete photodegradation of AMB (30ppm) at pH7 under UVA light irradiation for 30min while total mineralization in CO2 (>96%) was achieved after 24h of irradiation. Mn-TiO2 was 1.6-time more efficient than TiO2 Degussa P25. Product studies were also carried out by liquid chromatography coupled to electrospray high resolution mass spectrometry. Twenty-one photodegradation products were detected and identified. In addition, ionic chromatography analyses revealed the release of Br-, NH4+, and NO3- at respectively 97, 63 and 35% of the total Br, and N initially present in AMB. Finally, the reusability of the photocatalyst was also tested. After four cycles, the almost complete photodegradation of AMB was achieved showing that Mn-TiO2 was highly stable. This work brings new physical characteristics on Mn-TiO2 photocatalyst. Moreover, it is the first study investigating the photocatalytic degradation of recalcitrant AMB drug.

The clinical research on Bairui grain combined with ambroxol atomization inhalation treating acute attack patients of chronic bronchitis

Objective To observe the clinical effect of Bairui grain combined with ambroxol atomization inhalation treating acute attack of chronic bronchitis (wind heat attact the lung symptom). Methods A total of 150 patients with acute attack of chronic bronchitis who were admitted in our hospital from July 2015 to July 2018 were randomly divided into control and intervention groups (75 each group) by the random number table method. The control group received ambroxol atomization inhalatio based on the regular western medicine treatment; the intervention group took Bairui grain orally based on control group. Both of the two groups were treated for 2 weeks. Before and after the treatment, to score the clinical symptoms and wind-heat attact the lung symptom. Use pulmonary function meter to detect the ratio of FEV1 to estimated value (FEV1%) and FEV1/FVC; use ELISA to detect serum and sputum levels of TNF-α and IL-6. Record the extinction time of the symptoms (cough, wheezing, sputum, lung rumble) and evaluate the clinical efficacy. Results The total efficacy rate of intervention group was 98.6% (72/73), which was significantly higher than control group 88.9% (64/73) (χ2=4.354, P=0.037). The symptoms (cough, wheezing, sputum, lung rumble) extinction time of intervention group were significantly less than those of the control group (t values 5.331, 5.590, 5.841, 6.305, respectively, all Ps<0.01). After the treatment, scores of clinical symptoms (cough, wheeze, cough, cough) and symptoms of wind-heat attacking lung (cough, wheezing, fever, dry mouth, stuffy nose, runny nose) of intervention group were significantly lower than those of the control group (t values 4.990, 4.431, 5.221, 5.004, 5.652, 5.190, 5.311, 5.793, 5.643, respectively, all Ps<0.01). After treatment, the FEV1% (52.51% ± 5.63% vs. 47.30% ± 5.21%, t=8.931) and FEV1/FVC (61.57 ± 6.44 vs. 56.87 ±5.82, t=8.251) were significantly higher than the control group (P<0.01). The serum level of TNF-α, IL-6 (t values 5.331, 4.908) and the level of TNF-α, IL-6 (t values 6.001, 4.803) in sputum were significantly lower than those of the control group (P<0.01). Conclusions The Bairui grain combined with ambroxol atomization inhalation can decrease the inflammotory cytokine levels of the acute attack patients with chronic bronchitis (syndrome of wind-heat attacking lung symptome), improve clinical symptoms and enhance efficacy. Key words: Bronchitis, chronic; Bairui grain; Ambroxol; Nebulization inhalation therapy; Integrated Chinese traditional and western medicine therapy

Efficacy of ambroxol hydrochloride in the treatment of exacerbation of chronic obstructive pulmonary disease

Objective To observe the efficacy of ambroxol hydrochloride in the treatment of acute exacerbation of chronic obstructive pulmonary disease(COPD). Methods From January 2015 to December 2017, 84 patients with COPD exacerbation in Zhuji Central Hospital were selected and randomly divided into two groups according to the digital table, with 42 cases in each group.The control group was treated with routine therapy, the observation group was treated with ambroxol hydrochloride on the basis of routine treatment.The course of treatment in both two groups was 14 days.The clinical efficacy, clinical symptom disappearance time, pulmonary function index, inflammation index and adverse reaction were compared between the two groups. Results The total effective rate in the observation group was 95.24%(40/42), which was higher than that in the control group(78.57%, 33/42), and the difference was statistically significant(χ2=5.126, P 0.05). Conclusion Ambroxol hydrochloride can shorten the time of disappearance of clinical symptoms, improve the clinical efficacy and improve the pulmonary function and inflammation related indicators in the exacerbation period of COPD. Key words: Pulmonary disease, chronic obstructive; Respiratory function tests; Forced expiratory volume; Blood gas monitoring, transcutaneous; C-reactive protein; Neutrophil infiltration; Leukocytes; Ambroxol

Antitussive, expectorant, and anti-inflammatory effects of Adenophorae Radix powder in ICR mice

Ethnopharmacological relevanceAdenophora triphylla var. japonica is frequently used as an oriental medicinal plant in Korea, China, and Japan for its anti-inflammatory, antitussive, and hepatoprotective effects. Aim of the studyIn the present study, the antitussive, expectorant, and anti-inflammatory effects of AR powder were investigated using animal models to evaluate their potential to treat respiratory disorders. Materials and methodsAR powder was administered orally to mice once daily for 11 days, at dose levels of 400, 200, and 100 mg/kg. Theobromine (TB), ambroxol (AM) and dexamethasone (DEXA) were used as standard drugs for antitussive effects, expectorant effects and anti-inflammatory effects, respectively. Evaluations of antitussive effects were based on changes in body weight, the number of cough responses and the histopathology of the lung and trachea. Expectorant effects were based on changes in the body weight, macroscopic observations of body surface redness, the mucous secretion of the trachea and histopathology of lung (secondary bronchus). Anti-inflammatory effects were based on changes in the body weight, macroscopic observations involving redness and edema of the treated ear, absolute and relative ear weights and histopathology of the treated ears. ResultsAllergic acute inflammation and coughing induced by exposure to NH4OH and symptoms of xylene-induced contact dermatitis were significantly inhibited by treatment with AR powder in a dose-dependent manner. Histological analyses revealed that AR powder decreased the OD values in trachea lavage fluid, reduced body surface redness, thicknesses of intrapulmonary secondary bronchus mucosa, and the number of PAS-positive mucous producing cells. Overall, AR powder administered at 200 mg/kg displayed superior antitussive and expectorant effects as compared to TB (50 mg/kg), and AM (250 mg/kg). At the highest concentration (400 mg/kg) AR powder displayed only moderately improved anti-inflammatory activities as compared to DEXA (1 mg/kg). ConclusionThe results obtained in this study suggest that AR powder exerts dose-dependent, favorable antitussive, expectorant, and anti-inflammatory activities achieved through modulation of the activity of mast cells and respiratory mucous production. Therefore, AR powder may serve as a therapeutic agent in various respiratory disorders, especially those that occur as a result of environmental toxicants.

Uroprotective effect of ambroxol in cyclophosphamide-induced cystitis in mice.

Hemorrhagic cystitis (HC) is defined as any types of acute or chronic inflammation of urinary bladder with several reasons. One of the most common causes of HC is cyclophosphamide (CYP), an effective antineoplastic agent, due to its urotoxic potential. Ambroxol (AMB) is a mucoactive drug that has been used for numerous respiratory diseases. Besides its mucolytic activity, AMB is a potent antioxidant and antiinflammatory agent that is becoming more attractive for the treatment of several oxidative/inflammatory disorders. The aim of this study was to evaluate the uroprotective potential of AMB in CYP-induced HC. Male Balb/c mice were pretreated with AMB (30, 70, and 100mg/kg) once a day for 3 consecutive days before HC induction with CYP (300mg/kg). Mesna (30mg/kg;i.p.), only drug in the management of CYP-induced HC, was administered 20min before; 4 and 8h after cystitis induction. The urinary bladders were harvested and evaluated in functional, biochemical, and histological studies. CYP-induced HC markedly reduced acetylcholine (ACh)-induced contractions in detrusor strips and AMB at 100mg/kg caused a significant increase in the responsiveness to ACh. Pretreatment with AMB prevented the elevation of malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α) level, reduction of total glutathione (GSH) that induced by CYP. However, treatment with AMB did not improve the bladder weight and some histological parameters. These results suggest that AMB pretreatment could improve CYP-induced HC via antioxidant and antiinflammatory activities.