关键词: 非靶向代谢组学, 天山花楸水提物, 哮喘, 叉头状转录因子P3, 维甲酸相关孤儿受体γt

Abstract:

This study aims to investigate the effects of the water extract of Sorbus tianshanica Rupr. (STE) on airway inflammation in a murine model of allergic asthma and its potential underlying mechanisms. An asthma mouse model was established by ovalbumin induction. The mice were randomly assigned to six groups: control group, model group, positive control group treated with dexamethasone (2 mg/kg), low-dose STE group (1 g/kg), medium-dose STE group (2 g/kg), and high-dose STE group (4 g/kg). Mice in each group received the corresponding treatment, and after two weeks of continuous oral gavage, the expression levels of relevant inflammatory factors were assessed using ELISA, RT-qPCR and Western blot methods. In addition, untargeted metabolomic analysis combined with molecular docking using AutoDock software was performed to explore the potential targets and anti-asthmatic mechanisms of STE. ELISA results showed that, compared with control group, immunoglobulin E (IgE) in serum and interleukin-17A (IL-17A) levels in bronchoalveolar lavage fluid were markedly higher (P < 0.01), while IL-10 levels were significantly lower (P < 0.01) in model mice. High-dose STE treatment markedly suppressed IgE and IL-17A (P < 0.01) and boosted IL-10 levels (P < 0.01). RT-qPCR and Western blot results showed that, compared with the model group, the high-dose STE group significantly upregulated the expression of forkhead box protein P3 (FOXP3) (P < 0.01) and downregulated the expression of retinoid acid-related orphan receptor γt (RORγt) (P < 0.01) in lung tissues. Metabolomic and molecular docking analyses further revealed that STE may exert its effects by regulating fatty acid and amino acid metabolism pathways, inhibiting pro-inflammatory signaling, and enhancing anti-inflammatory mechanisms. In summary, STE improves airway inflammation by modulating the balance between T helper 17 (Th17) and regulatory T cells (Treg), upregulating the expression of anti-inflammatory factors IL-10 and FOXP3, and downregulating the activity of pro-inflammatory factors IL-17A and RORγt.

Key words: untargeted metabolomics, Sorbus tianschanica Rupr., asthma, FOXP3, RORγt