Apigenin Eos Inflammation Of Asthma Experimental Mice And Tgf-¦Â1 Affect The Mechanism

Objective To investigate the inhibitory effects and mechanism of apigenin on acute murine model of asthma. Methods Thirty-two healthy BALB/c mice were randomly divided into four groups (n = 8 per group), namely the control group, asthmatic group, high-dose apigenin group (20 mg.kg^-1.d^-1) and low-dose apigenin group (2 mg.kg^-1.d^-1). The murine asthmatic model was established by ovalbumin (OVA) sensitization and challenge. Acetylcholine (Ach) was administered by caudalis vein to measure the airway resistance 24 h after the last airway challenge. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of IL-4 and IL-13 in BALF and total IgE in serum. Total and differential cell counts in branchoalveolar lavage fluid (BALF) were measured by light microscopy. The airway inflammation was detected by haematoxylin and eosin (HE) staining. The signal Eotaxin in lung tissue was determined by Western blot analysis; The signal chemokine receptors 3 ( CCR3 ) were determined by immunohistochemisty. Results Airway heperreactivity, airway eosinophilia, the levels of total serum IgE and BALF IL-4 and IL-13, and lung Eotaxin,CCR3 expression were significantly increased in the asthmatic group compared with those in the control group (P < 0. 05). Pretreatment of the asthmatic group with apigenin obviously decreased the above indexes (P < 0. 05). Also, there were significant differences between the low- and high-dose apigenin groups (P < 0. 05). Conclusions Apigenin may inhibit airway inflammation and hyperreactivity by down-regulating the expression of pulmonary Eotaxin,CCR3 and Th2 cytokines, which is a potential drug for asthma therapy.Part TwoThe effect of apigenin on airway inflammation and remodelling in a murine model of chronic asthmaObjective To investigate the influence of apigenin on airway inflammation and remodelling in chronic murine model of asthma. Methods BALB/c mice were randomly divided into four groups. control group, OVA group, apigenin group and budesonide group. Mice were sensitized and challenged by OVA. Mice in treatment groups were given apigenin (20 mg.kg-1.d-1) by ip. Airway responsiveness to acetylcholine chloride was investigate 24 hours after the last OVA challenge. The sections were stained with either hematoxylin & eosin to investigate the inflammatory cell infiltrates, PAS to quantify airway global cells and Masson's trichrome to investigate collagen deposition in the lungs. Total collagen content of the lung was determined by hydroxyproline assay. Total immunoglobulin E (IgE) levels in serum and the IL-4, IL-13 level in BALF were measured by ELISA. The expression ofα-SMA in lungs was evaluated by immunohistochemistry. The TGF-β1 of lungs was evaluated by WB. Results The airway resistance generated by administration of ACh at doses from 30 to 270 mg/kg increased significantly in the OVA group compared with the control group (P< 0.01). Treatment with apigenin or budesonide led to a sharp decrease in airway resistance compared with the OVA group (P<0.05). There were no significant differences in airway resistance between the apigenin group and budesonide group (P>0.05). The number of eosinophils and total inflammatory cells in BALF in the OVA group increased significantly compared with the control group (P<0.01), and was significantly decreased by treatment with apigenin or budesonide (P< 0.01). There were no significant differences between the apigenin group and budesonide group (P>0.05).Total serum IgE and IL-4, IL-13 in BALF were significantly increased in OVA-sensitized/challenged mice compared with the control group (P<0.01). Administration of apigenin or budesonide reduced the levels of total serum IgE compared with the OVA group (P<0.05). There were no significant differences in the levels of total serum IgE between apigenin group and budesonide group (P>0.05). The mean area of Masson's trichrome staining (collagen deposition) in the OVA group was significantly enhanced compared with the negative control group (P<0.01). Administration of apigenin or budesonide caused a marked reduction in collagen deposition compared with the OVA group (P<0.05). Total lung hydroxyproline content in the OVA group was significantly greater than that in the control group (P<0.01). In contrast, treatment with apigenin or budesonide significantly reduced total lung hydroxyproline content compared with the OVA group (P<0.05). The area of theα-SMA-stained smooth muscle layer in OVA-sensitized and challenged mice was significantly greater than that in the saline-treated control (P<0.01). Administration of apigenin or budesonide decreased theα-SMA immunostained area compared with the OVA group (P<0.05). The protein levels of TGF-β1 in the lungs in the OVA group increased significantly compared with that in the control group (P<0.05). Treatment with apigenin or budesonide decreased the protein levels of TGF-β1 compared with that in the OVA group (P<0.05). Conclusion Apigenin may alleviate the airway inflammation, AHR and airway remodelling in a murine model of chronic asthma , by down-regulating the expression levels of TGF-β1...