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.

Anti‐inflammatory, antioxidant, and immunomodulatory effects of curcumin in ovalbumin‐sensitized rat

“…These results indicate comparable or even higher anti‐inflammatory and antioxidant effects of curcumin on asthmatic rats compared to the effect of dexamethasone along with more specific immunomodulatory effect which is another important evidence of the possible preventive effect of curcumin in asthma. In this study, the dose of dexamethasone was 0.25 mg/kg/day during 21 days sensitization period (1.25 μg/mL in drinking water of animals) which was equal or even higher than previous studies which used 0.5 mg/kg/day orally only for 3 days during sensitization period or 1 mg/kg/day intraperitoneally for 7 days in a 77‐day sensitization period in mice . In addition, dexamethasone at the dose administered in this study affected almost all measured parameters which suggest to be an effective dose for this substance.…”

Protective effects of ascorbic acid and calcitriol combination on airway remodelling in ovalbumin-induced chronic asthma

“…For induction of a chronic model of asthma in mice, a protocol of immunization with OVA was used (Mohammadian et al 2016(Mohammadian et al , 2019Kianmehr et al 2016Kianmehr et al , 2017Kianian et al 2019aKianian et al , 2019b. Briefly, except animals in the control group, others were sensitized by intraperitoneal injection of 10 mg OVA and 2 mg aluminium hydroxide (Sigma, USA) on days 0 and 14.…”

Interleukin‐16 aggravates ovalbumin‐induced allergic inflammation by enhancing Th2 and Th17 cytokine production in a mouse model

“…Th17 cells secrete several cytokines including IL‐17 (also known as IL‐17A), IL‐22, IL‐6 and tumor necrosis factor α . As effective inducers of inflammation, Th17 and IL‐17 are significantly associated with asthma cells and have been considered the definitive factors of severe asthma . Moreover, Th17 cytokines induce the release of pro‐fibrotic cytokines from human eosinophils in asthmatics …”

“…As effective inducers of inflammation, Th17 and IL-17 are significantly associated with asthma cells and have been considered the definitive factors of severe asthma. [11][12][13][14] Moreover, Th17 cytokines induce the release of pro-fibrotic cytokines from human eosinophils in asthmatics. 15 Interleukin-16 is a pro-inflammatory cytokine that is produced by many cells such as the lymphocytes, monocytes, eosinophils, mast cells and airway epithelial cells in individuals with asthma.…”