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The Effect of Zataria multiflora on Th1/Th2 and Th17/T Regulatory in a Mouse Model of Allergic Asthma.

ABSTRACT: Asthma is a chronic inflammatory disease with no definite treatment and more research is needed to overcome this condition. The aim of this study was to investigate the effect of the extract of Zataria multiflora (Z. multiflora) as a medicinal plant on cytokine genes expression in an experimental mouse model of asthma. Adult mice were randomly divided into the following groups: control (C), untreated asthma (A), asthmatic groups treated with dexamethasone (D) and Z. multiflora extract (200, 400, and 800 μg/mL; Z1, Z2, and Z3, respectively), (for groups C, A, and D n = 5 and for groups Z1, Z2, and Z3 n = 6). For induction of the mouse model of asthma, animals were sensitized with intraperitoneal injection and inhalation of ovalbumin (OVA). The number of T helper (Th) subtype cells (using flow cytometry) and the levels of IFN-γ, FOXP3, IL-4, TGF-β, IL-17 gene expression (by real time PCR) were assessed in mice splenocytes. The observed changes in spleen cells of group A compared to group C were increased number of Th2 and Th17 cells, enhancement of gene expression of IL-4, IL-17, and TGF-β (p < 0.001 for all cases), reduction of Th1 cells and Th1/Th2 ratio (p < 0.001 for both cases) and decrease in gene expression of IFN-γ, FOXP3 and IFN-γ/IL-4 ratio (p < 0.01 for IFN-γ and p < 0.001 for other cases). The observed changes in spleen cells of treated compared to untreated A group were enhancement of Treg cells and Th1/Th2 ratio (p < 0.001 for both cases), increase in IFN-γ (p < 0.05) and FOXP3 (p < 0.001) gene expression and IFN-γ/IL-4 ratio (p < 0.01) as well as reduction of Th2 and Th17 cells (p < 0.01 to p < 0.001), decrease gene expression of IL-4, IL-17, and TGF-β (p < 0.05 to p < 0.001). The findings showed that the extract of Z. multiflora decreased pro-inflammatory cytokines in asthma (IL-4 and IL-17 and TGF-β) but increased anti-inflammatory cytokines (IFN-γ) gene expression and the number of Treg (FOXP3) in splenocytes of asthmatic mice which may indicate the specific therapeutic effect of the plant extract in allergy, autoimmunity, and infectious diseases via potentiating Th1 and suppressing Th2 and Th17 cells.

SUBMITTER: Kianmehr M

PROVIDER: S-EPMC5545581 | biostudies-other | 2017

REPOSITORIES: biostudies-other

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Project description:ObjectiveMacmoondongtang has been used as a traditional medicine to treat pulmonary disease in Korea. However, the mechanism underlying its therapeutic effect has yet to be reported. In the present study, the role of macmoondongtang as a respiratory medicine, especially as an anti-asthmatic agent, has been attributed to the down-regulation of interleukin (IL)-4 and tumor necrosis factor (TNF)-α.Materials & methodsBALB/c mice were divided into five groups: control, asthma-induced control, dexamethasone treatment, treatment with 150 mg/kg macmoondongtang, and treatment with 1500 mg/kg macmoondongtang. To evaluate the anti-asthmatic effect of macmoondongtang, we investigated its suppressive or inhibitory effects against typical asthmatic changes such as differential cell count in bronchioalveolar fluid (BALF), serum IgE levels, lung morphology, expression of Th1/Th2 cell transcription factors such as T-bet and GATA-3, and Th1-/Th2-/Th17-related cytokines such as interferon (IFN)-γ, IL-12p40, IL-4, -5, -13, TNF-α, and IL-6. The active ingredients in macmoondongtang were further analyzed.ResultsMacmoondongtang treatment down-regulated serum IgE level, a very important marker of hyper-responsiveness. It reversed typical morphological changes such as mucous hypersecretion, lung epithelial cell hyperplasia, and inflammatory cell infiltration near bronchioalveolar space and veins. Macmoondongtang significantly decreased neutrophil count in BALF, as well as reduced T-bet, IFN-γ, and TNF-α expression in the lung. It also showed a dose-dependent control of inflammatory cells in BALF, controlled the expression of IL-12, IL-4, and IL-5 genes in the lung, and the protein expression of IL12p40, GATA-3, IL-4, IL-5, and IL-13. The component analysis revealed glycyrrhizin and liquiritin as the active ingredients.ConclusionsMacmoondongtang treatment alleviates asthma symptoms and modulate the Th1-/Th2- related cytokines. Glycyrrhizin and liquiritin could be the major the active therapeutic components.

Project description:Background:Asthma, a common respiratory disease, is harmful biological effect to our health. As a traditional Chinese medicine for asthma, Majie cataplasm could alleviate the symptoms of asthma and its compositions have immunomodulatory effects. Previous experiments showed that Majie cataplasm was an effective approach to mitigate asthma airway remodeling and had the potential to regulate Th2 cytokines of IL-5 and IL-13. Therefore, our further research focuses on the explanation about the regulatory effect of Majie cataplasm on reshaping Th1/Th2 through their related transcription factors. Methods:In this experiment, the launch of asthma model was made by inducing with Ovalbumin (OVA) in C57 mice (n?=?40), including 4 groups: the untreated control group (n?=?10), the asthma model group (n?=?10), the dexamethasone group (n?=?10) and the Majie cataplasm group (n?=?10). After the intervention, all groups of animals got detected for serum IgE levels, and HE staining of lung tissues was to observe and examine pathological changes. Meanwhile, we analyzed the secretion of IL-4+ T cells and IFN-?+ T cells in spleen by flow cytometry. The expressions of transcription factor STAT6 mRNA, GATA-3 mRNA and T-bet mRNA in lung tissues was tested by PCR, and western blot had been used to detect levels of JAK2 and STAT3. Results:We found that Majie cataplasm eased the content of serum IgE and lung inflammation. It could lower the increased number of IL-4+ T cells and IFN-?+ T cells (P?<?0.0001, P?<?0.01) in asthmatic mice and curb the expression of STAT6 mRNA and GATA-3 (P?<?0.0001, P?<?0.01) mRNA as well as the protein levels of JAK2 (P?<?0.001) and the ratio of pSTAT3/STAT3 (P?<?0.05). Besides, Majie cataplasm made its mark on T-bet mRNA by improving it (P?<?0.0001). Conclusion:These data suggest that Majie cataplasm exert an anti-inflammatory effect of Th2 by rebalancing Th1/Th2 through corresponding transcription factor STAT6, GATA-3, STAT3, and T-bet, which providing a strong cornerstone for asthma control.

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The Effect of Zataria multiflora on Th1/Th2 and Th17/T Regulatory in a Mouse Model of Allergic Asthma.

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