[Asthma-alleviating effects of Poria cocos based on network pharmacology and gut microbiota]

This study investigated the asthma-alleviating effects of Poria cocos from the perspectives of immuno-inflammation and gut microbiota(GM), providing a theoretical basis for its rational clinical use. Male Balb/c mice were randomly divided into normal, model, positive control(montelukast sodium, 1.5 mg·kg~(-1)), low-dose P. cocos(0.057 g·kg~(-1)), medium-dose P. cocos(0.114 g·kg~(-1)), and high-dose P. cocos(0.227 g·kg~(-1)) group. Except for the normal group, the other groups were sensitized with ovalbumin(OVA) by intraperitoneal injection combined with nebulization to establish an asthma model, and treated with the corresponding drugs. After modeling, cough and wheezing indices, lung function, and asthma characteristic indicators including immunoglobulin E(IgE), interferon-γ(IFN-γ), interleukin 4(IL4), and interleukin 10(IL10) levels were measured. Lung tissue pathology was observed by hematoxylin-eosin(HE) and Masson staining. Quantitative real-time PCR(qRT-PCR) was used to detect airway inflammation-and remodeling-related mRNA levels in lung tissue. Levels of 12 inflammatory factors in serum and bronchoalveolar lavage fluid were detected by multiplex assay. Furthermore, the asthma-alleviating mechanism of P. cocos was analyzed by network pharmacology and GM 16S rRNA sequencing. RESULTS:: showed that P. cocos reduced cough frequency in asthmatic mice, improved lung function, alleviated pathological damage in lung tissue, decreased serum IgE and IL 4 levels, increased IL 10 and IFN-γ levels, and multi-target regulated related inflammatory factors in serum and alveolar lavage fluid, maintaining immune homeostasis. Network pharmacology predicted that P. cocos exerts its asthma-alleviating effects via inflammation regulation pathways. GM sequencing showed that P. cocos effectively alleviated dysbiosis induced by OVA sensitization, significantly downregulated Muribaculum intestinale and Alistipes inops, and correlation analysis revealed both were positively correlated with pro-inflammatory factors. Therefore, it is speculated that P. cocos restores intestinal microecological homeostasis by reducing levels of M. intestinale and A. inops, decreases pro-inflammatory factor production, blocks the inflammatory cascade, and thereby exerts its asthma-alleviating effects.