Multi-omics analysis reveals therapeutic mechanisms of sipeimine in ovalbumin-induced asthmatic rats.

内容摘要

Asthma, as a persistent inflammatory airway disease, constitutes a significant burden in the field of global public health. Fritillaria Bulbus is a traditional Chinese medicine with efficacy in treating coughs, dissolving phlegm, and alleviating asthma. Sipeimine (SIP) is one of its isosteroidal alkaloids, has demonstrated antitussive, anti-inflammatory, and pulmonary protective effects. Nevertheless, the efficacy of SIP in asthma and its potential mechanisms have not yet been fully clarified. The research seeks to investigate the therapeutic potential and action mechanism of SIP for asthma using a comprehensive multi-omics strategy. The asthma rat model was induced using ovalbumin. Subsequently, SIP was administered orally for 14 consecutive days. Biochemical assays and pulmonary histopathological examinations assessed anti-asthmatic efficacy. An integrated strategy combining metabolomics, 16S rRNA sequencing, and transcriptomics was employed to identify potential mechanisms underlying SIP treatment in asthma. Real-time quantitative PCR and western blotting were used to validate key genes and proteins. SIP significantly alleviated histological damage in lung tissue, including inflammation, collagen deposition, and mucus secretion. Metabolomics analysis indicated that SIP normalized metabolite profiles and modulated pathways associated with ferroptosis. Additionally, SIP improved gut microbiota dysbiosis by restoring Lactobacillus abundance, reducing the richness of Muribaculaceae, Romboutsia, and Clostridium_sensu_stricto_1 genera. Transcriptomic analysis revealed that SIP ameliorated asthma by suppressing the IL-17 signaling pathway. SIP exhibits significant therapeutic effects against asthma, potentially by reducing inflammation, altering gut microbiota and metabolites, and inhibiting ferroptosis and IL-17 signaling.