Zataria multiflora affects pulmonary function tests, respiratory symptoms, bronchodilator drugs use and hematological parameters in chronic obstructive pulmonary disease patients: A randomized doubled-blind clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Zataria multiflora is employed as an antitussive, anti-spasmodic, analgesic and etc. Agent in traditional medicine. The modern medical studies are also confirmed effects of this plant for treatment of respiratory problems via anti-inflammatory, anti-oxidant and immunomodulatory properties. AIM OF STUDY: We evaluated efficacy of Z. multiflora on tests of pulmonary function, respiratory symptoms, inhaled bronchodilator drugs use, and hematological factors in COPD patients. METHODS: Patients (n = 45) were randomly grouped in the following three groups: placebo group (P), groups received Z. multiflora extract 3 and 6 mg/kg/day (Z3 and Z6). FEV1 and MEF25-75, respiratory symptoms, inhaled bronchodilator drugs use and hematological factors were evaluated before and 1-2 months after treatment. RESULTS: Z. multiflora led to significant enhancement of FEV1 (p < 0.05 to p < 0.01). Respiratory symptoms were also considerably ameliorated following treatment with extracts for 1 and 2 months compared to baseline values (p < 0.05 to p < 0.001). In groups received extract, inhaled bronchodilator drugs use was remarkably declined at the end of study (both, p < 0.05). Reduction of total WBC was observed 1-2 months after treatment in treated groups with extract compared to baseline values (p < 0.05 to p < 0.001). Neutrophils were remarkably declined in Z3 and Z6 groups after 2-monthes compared to 1-month treatment (p < 0.05 to p < 0.01). CONCLUSION: The evidence show therapeutic effect of this herb on COPD patients which could be result from properties that help to decrease inflammation.

Efficacy of Herbal Medicines on Lung Function in Asthma: a systematic review and meta-analysis of randomized controlled trials.

Objectives: The present study was designed to conduct a comprehensive systematic review and meta-analysis to assess the efficacy of herbal medicines as add-on therapy on lung function in asthmatic patients. Methods: A comprehensive search of online databases was performed up to December 2021 to identify randomized controlled trials that used orally herbal preparations for asthma as add-on therapy. Studies were assessed for methodological quality using the Cochrane Collaboration's Risk of Bias tool. The main outcome was percent predicted value of forced expiratory volume (% predicted FEV1). Pooled weighted mean difference (WMD) estimate with corresponding 95% confidence interval (CI) was calculated using inverse-variance weights method while random effects meta-analysis was used, taking into account clinical and conceptual heterogeneity. Results: As a result, 1,525 studies were identified. 169 studies were reviewed in-depth and 23 studies met our systematic review inclusion criteria. Finally, nine randomized controlled trials were included in the meta-analysis. Findings indicated that use of herbal medicines in patients with asthma significantly improved % predicted FEV1 (WMD 3.73, 95% CI 1.76-5.70), with no evidence for significant heterogeneity (p = 0.56 [Q statistic], I2 = 0.0%). In subgroup analysis by age, improvement in % predicted FEV1 was higher and significant in adults (WMD 5.16; 95% CI 2.68-7.63) compared to children (WMD = 1.27; 95% CI -1.98-4.51). Sensitivity analysis showed the significant effect of herbal medicine consumption on improving FEV1 was consistently (range of summary WMDs 3.27-4.59), indicating that the meta-analysis model was robust. There was no evidence of publication bias both visually and statistically. Conclusion: Findings support, the complementary use of herbal medicines resulted in significant improvement in the lung function compared to standard treatment in asthmatic patients with no considerable adverse events. This improvement is more likely to be observed amongst adults.

The effect of two-month treatment with Zataria multiflora on inflammatory cytokines, pulmonary function testes and respiratory symptoms in patients with chronic obstructive pulmonary disease (COPD).

ETHNOPHARMACOLOGICAL RELEVANCE: Zataria multiflora Boiss. (Z. multiflora) is a valuable medicinal plant that has been used in Iranian traditional and folk medicine as an antiseptic, carminative, diaphoretic, diuretic, anti-spasmodic and analgesic herbal medicine. This plant has been also used to relieve cough in common cold and respiratory tract disorders. The previous studies reported the pharmacological effects of Z. multiflora such as anti-inflammatory and anti-oxidant properties in respiratory disorders in animal models and clinical studies. AIM OF THE STUDY: The effects of Z. multiflora extract on inflammatory cytokines, pulmonary function tests (PFT), and respiratory symptoms in chronic obstructive pulmonary diseases (COPD) patients were investigated. MATERIALS AND METHODS: COPD patients (41 cases) were divided to three groups including placebo group (P) and groups received 3 and 6 mg/kg/day Z. multiflora extract (Z3 and Z6) for two months. Inflammatory cytokines, PFT values, and respiratory symptoms were assessed before treatment (stage 0), one (stage I) and two (stage II) months after treatment. RESULTS: Serum levels of TNF-α and IL-8 were significantly decreased after two months treatment compared to baseline values in Z3 and Z6 groups. The PFT values including forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were significantly increased during two months treatment with Z3 and Z6. The peak expiratory flow (PEF) was also significantly increased after one-month treatment with Z6. The respiratory symptoms including cough, chest tightness, modified medical research council (mMRC) dyspnea scale were significantly improved after one and two treatments with both doses of Z. multiflora compared to baseline values. CONCLUSION: The results suggest the potential therapeutic effect of Z. multiflora in COPD patients through reduction of inflammatory cytokines, increasing PFT values and improvement of respiratory symptoms.

A Randomized, Doubled-Blind Clinical Trial on the Effect of Zataria multiflora on Clinical Symptoms, Oxidative Stress, and C-Reactive Protein in COPD Patients.

The effects of Zataria multiflora on clinical symptoms, pulmonary function tests, oxidative stress, and C-reactive protein levels in chronic obstructive pulmonary disease (COPD) patients were evaluated. Forty-five patients were allocated to 3 groups: placebo group and 2 groups that received 3 and 6 mg/kg/day Z. multiflora extract (Z3 and Z6) for 2 months. Clinical symptoms, pulmonary function tests, oxidative stress, and serum C-reactive protein levels were evaluated pretreatment (step 0) and 1 (step I) and 2 (step II) months after treatment. Clinical symptoms including breathlessness and chest wheeze in Z3- and Z6-treated groups and sputum production only in the Z6-treated group were significantly improved 1 and 2 months after treatment compared with baseline values (P < .01 to P < .001). The FEV1 was significantly increased after 2 months of treatment with Z3 and Z6 (P < .05 to P < .01). Malondialdehyde and nitrite levels were significantly decreased after a 2-month treatment with Z6 compared with step 0 (P < .05 to P < .01). The thiol contents in the Z6 group as well as superoxide dismutase and catalase activities in both groups treated with the extract were significantly increased in step II compared with step 0 (P < .05 to P < .01). The C-reactive protein level at the end of the study was significantly reduced compared with the step 0 in both treated groups (P < .05 for both cases). Two-month treatment with Z. multiflora improved clinical symptoms, pulmonary function tests, oxidative stress, and C-reactive protein in COPD patients. The results suggest that this herbal medicine could be of therapeutic value as a preventive drug for the treatment of COPD.

A Viewpoint on the Leaky Gut Syndrome to Treat Allergic Asthma: A Novel Opinion.

Asthma is a common respiratory disease characterized by airway inflammation, airway hyperreactivity, and reversible airflow obstruction. Despite current treatments, the prevalence of asthma has increased markedly over decades. According to the theories proposed to explain the pathophysiology of autoimmune diseases in integrative medicine, leaky gut syndrome is a phenomenon of increased intestinal permeability due to the disruption of tight junctions and is thought to be related to many chronic diseases, such as food intolerance, inflammatory bowel disease, rheumatoid arthritis, asthma, and other autoimmune disease. One of the classical approaches used by integrative physicians to treat leaky gut syndrome is to repair intestinal permeability to prevent allergic cascade. Due to several mechanisms that have been mentioned in the protective effects of plant gums and plantain family seeds on the intestinal epithelium, we can propose an effective management for leaky gut syndrome to treat asthma.

Effect of Borago Officinalis Extract on Moderate Persistent Asthma: A Phase two Randomized, Double Blind, Placebo-Controlled Clinical Trial.

BACKGROUND: Borago officinalis and its derivatives are used in folk medicine to treat asthma because of its special effect on allergic disorders. It suppresses the tumor necrosis factor-alpha (TNF-alpha) and delivers gamma-linolenic acid. The objective of this clinical trial was to determine the effect of Borago officinalis on clinical and physiological findings in moderate persistent asthma. MATERIALS AND METHODS: This prospective, randomized, double blind, placebo-controlled, clinical trial was conducted on patients aged 15-90 years with moderate asthma and forced expiratory volume in one second (FEV1) of 60-79% of predicted who presented to a sub-specialty clinic of pulmonary medicine. We randomly allocated subjects to receive either Borago extract (5 mL three times a day) or a matched placebo for one month. The primary outcome was the asthma control test (ACT) score and fractional exhaled nitric oxide (FENO) test. Secondary outcomes included clinical findings, spirometry, and sputum cytology including inflammatory cells. RESULTS: Thirty-eight subjects with a mean age of 46.8±15.3 years and mean duration of asthma of 71±103 months were enrolled in our study. Cough, dyspnea, wheezing, nocturnal symptoms, and airway hyper-responsiveness reduced significantly in the Borago group after the treatment and ACT scores improved significantly (10.8±5.26 before and 15.4±5.12 after the trial). Flare up of asthma and emergency department visits in the Borago group also decreased significantly (3.6±2.33 to 2±1.86 flare ups per month and 0.62±0.9 to 0.05±0.23 for emergency department visits per month). Physiological parameters including spirometry, FENO, and sputum cytology including eosinophil and neutrophil did not change significantly. CONCLUSION: Borago improved the clinical findings of asthma, but it was not able to suppress the inflammation involved in asthma.

Effect of verapamil on bronchial goblet cells of asthma: an experimental study on sensitized animals.

INTRODUCTION: Goblet cell hyperplasia (GCH) and mucus hypersecretion in the airway is recognized as an important contributor to morbidity and mortality in asthma and COPD. Verapamil is a calcium channel blocker that binds to the alpha-subunit of L-type calcium channels and inhibits the mucin gene via the calmodulin and CaM kinase pathway. The objective of this study was to determine the in vivo effect of verapamil on GCH and eosinophilic inflammation in sensitized mice. METHODS: Male BALB/c mice were sensitized to ovalbumin using the standard method. Two groups of animals were received verapamil via an intramuscular injection: 1-low dose (0.5 mg/kg/day for two weeks), 2-high dose (1.5 mg/kg/day for two weeks). Serum and bronchoalveolar lavage fluid (BALF) was collected and analyzed for inflammatory cells, interferon-γ and IL-4. The left lung was sent for histopathological evaluation, especially for periodic acid-Schiff (PAS), to identify goblet cells in the epithelium. The degree of inflammatory cell infiltration, including eosinophils, mucus plugging, and smooth muscle thickness of the airways were classified on a semi quantitative scale. RESULTS: Inflammatory cell infiltration in peribronchial and perivascular areas was observed in all sensitized groups. Eosinophils percentage in the BALF significantly decreased in verapamil-treated mice compared with sensitized mice (from 19.8% in asthmatic to 5.4% for low dose and 4.4% for high dose). The ratio of airway goblet cells per epithelial cells were significantly lower in verapamil-treated mice versus sensitized mice (1.57±1.30% for low dose; 1.50±0.93% for high dose versus 12.93±7.55%, P<0.05, respectively). Mucus production of goblet cells decreased significantly in verapamil-treated mice versus sensitized mice (mean score was 1.45±0.30 for low dose; 0.81±1.00 for high dose versus 2.85±0.86 in the sensitized control group, P<0.05, respectively). The concentration of serum and BALF-IFN-γ in verapamil-treated mice markedly increased by the verapamil treatment when compared to sensitized mice (15.1±0.43 versus 4.7±0.96, P<0.05 and 91.8±47.7 versus 14.8±4.6, P<0.01, respectively). CONCLUSION: Verapamil is a useful drug with therapeutic targeting on GCH and a potential way to limit mucous production and improve bronchial inflammation.