Platycodonis Radix Total Saponins Regulates Th17/Treg Immune Imbalance to Alleviate Airway Inflammation in Asthmatic Mice
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Graphical Abstract
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Abstract
OBJECTIVE To explore whether Platycodonis Radix total saponins regulate Th17/Treg balance in asthma by mediating Notch pathway. METHODS Forty-eight BALB/c mice were randomly divided into namely normal control group, model group, Platycodonis Radix total saponins low dose, medium dose and high dose groups(15, 30, 60 mg·kg-1) and dexamethasone group, 8 mice in each group. Mice asthma model was established by ovalbumin sensitization, and airway hyperreactivity was measured after 8 weeks of corresponding drug intervention. The samples were collected and used for bronchoalveolar lavage fluid(BALF) cell count, ELISA, HE, PAS and Masson staining. Flow cytometry was used to detect the percentage of Th17 and Treg cells and the change of Th17/Treg ratio in the lung tissues of mice. The expression levels of Notch1, Jagged1, RORγt and Foxp3 were detected by qPCR, and the expression levels of Notch1, Jagged1, Hes1 and RORγt, Foxp3, IL-10 and IL-17 were detected by Western blotting. RESULTS Compared with model group, Platycodonis Radix total saponins medium and high dose groups airway resistance significantly reduced, the number of inflammatory cells and the content of inflammatory factors IL-4, IL-5 and IL-13 in BALF decreased, and the contents of IL-17, IL-6 and IgE in serum decreased. The levels of INF-γ in BALF and IL-10 in serum were significantly increased(P<0.05 or P<0.01). The results of HE, PAS and Masson experiments showed that the high dose group of Platycodonis Radix total saponins and dexamethasone group could significantly alleviate inflammatory cell infiltration and bronchial membrane destruction, reduce goblet cell proliferation, and reduce the degree of collagen fiber release from tissues. Flow cytometry results showed that the number of Th17 cells and Th17/Treg ratio in medium and high dose groups of Platycodonis Radix total saponins were significantly decreased, and the number of Treg cells was significantly increased(P<0.05 or P<0.01). qPCR and Western blotting results showed that the mRNA levels of Notch1, Jagged1, RORγt and the protein expression levels of Notch1, Jagged1, Hes1, RORγt, IL-10 and IL-17 in lung tissues of mice treated with Platycodonis Radix total saponins were significantly decreased, the expression levels of Foxp3 mRNA and Foxp3 protein were significantly increased(P<0.05 or P<0.01). CONCLUSION Platycodonis Radix total saponins can mediate the Notch pathway to regulate Th17/Treg balance in asthma, thus reducing airway inflammation and inhibiting asthma attack.
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