Zataria multiflora affects clinical symptoms, oxidative stress and cytokines in asthmatic patient: A randomized, double blind, placebo-controlled, phase II clinical trial

Abstract

Background

Z. multiflora effect on clinical symptoms, pulmonary function tests (PFT), oxidative stress and cytokine levels in asthmatic patients were evaluated.

Methods

36 asthmatic patients were divided to; placebo group (P), two groups treated with Z. multiflora extract (5 and 10 mg/kg/day, as Z5 and Z10, respectively), (n = 12 in each group). Medications were administered three times a day for two months and several parameters were evaluated before treatment (step 0), one (step 1) and two months (step 2) after treatment.

Results

Clinical symptoms and PFTs were significantly improved in Z5 and Z10 groups in steps 1 and 2 compared to step 0 (p < 0.05 to p < 0.001). Improvement of oxidative stress, cytokines levels and their gene expression after treatment with both doses of extract were observed in step 2 compared to step 0 (p < 0.05 to p < 0.001).

Conclusion

These results indicated therapeutic value of Z. multiflora for the management of asthma.

Introduction

Asthma is a common chronic inflammatory disease which about 334 million people suffer from this disease in the world [1], [2]. The prevalence of asthma in developed countries is approximately 10% in adults while in developing countries; its prevalence is lower but rapidly rising. The prevalence of asthma in Iran is 4.5% in men and 1.4% in women [2], [3]. In susceptible individual, lung inflammation led to repeated attacks of wheezing, dyspnea, chest tightness and coughing, especially at night or in the morning. These symptoms are relatively reversible by medication or spontaneously [4], [5]. Cytokines play a key role in organizing chronic inflammation in asthma by activating and surviving multiple inflammatory cells in the respiratory system. In asthmatic patients, the number of CD4 cells (Th2 subtype) increases in airways. Th2 cells mainly secrete cytokines interleukin (IL)-4, IL-5, IL-9 and IL-13. In these diseases, IL-4 increased bronchial responsiveness and mucus secretion [6], [7], [8]. Anti-inflammatory cytokines (IL-10, IL-12, and interferon-γ (IFN-γ) values in asthma were decreased and the decline in production of IFN-γ has a direct relationship to the severity of the disease. IL-10 also suppresses the production of a number of inflammatory cytokines [9], [10], [11]. In addition, there is an increased oxidative stress in asthma characterized by increased oxidized glutathione level in the lung, and increased nitric oxide production in the exhalation air. Changes in antioxidant defense have also been reported in asthma, including decreasing the antioxidant capacity, glutathione peroxidase (GPx) and the activity of superoxide dismutase (SOD) in the blood [12], [13], [14].

Zataria multiflora Boiss. (Z. multiflora), (Shirazi thyme) is a grassy and perennial plant that is recognized by wooden base and firm stalk with a grayish-white skin and height of 40 to 80 cm, very branched, round or elliptical indumentums leaves, with aromatic smell. The essential oils of Z. multiflora contain significant amounts of thymol and carvacrol. In addition, P-cymene, linalool, caryophyllene, γ-terpinene and borneol are other main components of this plant. Ecological variation, stage of plant growth, preparation method and other factors may influence quantitatively and qualitatively of oil composition [16]. Z. multiflora in traditional medicine is used as antiseptic, antispasmodic and treatment of cold and cough [15].

The effects of Z. multiflora on tracheal responsiveness, cytokines (inflammatory and anti- inflammatory), total and differential white blood cells (WBC) in sensitized guinea pigs have been demonstrated. The extract of Z. multiflora in the animal model of chronic obstructive pulmonary disease (COPD) resulted in a decrease in the total number of WBC, neutrophils and eosinophil in blood and bronchoalveolar lavage fluid. This plant also reduced the response of smooth muscle and improved emphysema [16], [17], [18]. In several studies, it has been reported that Z. multiflora and its constituents can be considered as a potential source of natural antioxidants for traditional and pharmaceutical uses [19], [20]. In animal studies, it decreased nitrite and oxidant factors and increases antioxidant agents [17], [21], [22], [23].

The increasing prevalence of asthma around the world, the high burden of the disease on the patients, and the high costs of health care, required serious research about the mechanism and treatment of this disease. Thus, the goal of this study was to evaluate the effect of Z. multiflora on clinical symptoms, pulmonary function tests, oxidative stress and cytokine levels in asthmatic patients during two months treatment.