Integrating metabolomics, network pharmacology and pharmacological verification analysis provides new insights into the anti-inflammatory and anti-tussive properties of Fritillaria cirrhosa bulbs

Fritillaria cirrhosa bulbs, referred to as Chuanbeimu in traditional Chinese medicine (TCM), are extensively used for recognized anti-inflammatory and anti-tussive effects. Both Songbei (SB) and Qingbei (QB), which are from this plant, have been used separately in medicine. However, the differences and similarities in their bioactive components and anti-inflammatory effects remain unclear. We aimed to analyse the metabolic profiles of F. cirrhosa bulbs across different growth years and explore the anti-inflammatory and anti-tussive properties of two distinct medicinal materials. With nontargeted metabolic technology, the main components of bulbs were detected. Principal component analysis (PCA) and pathway enrichment analysis were carried out to determine the differentially expressed metabolites between growth years. Network pharmacology was subsequently used to analyse the relationships among the components, diseases, key targets, and metabolic pathways by constructing a network model. The effects of drug-containing serum on cellular inflammatory factors were analysed through in vitro assays. A total of 1349 compounds were identified from the different bulb samples. PCA revealed metabolic differences between SB bulbs (1- and 2-year-old) and QB bulbs (3-, 4-, and 5-year-old). Notably, 4-methoxycinnamaldehyde, tenuifoliside A, LysoPC 20:4, and morpholine-4-carboximidamide hydrobromide were identified as potential components for distinguishing SB and QB. Network pharmacology revealed more common targets related to anti-inflammatory (PPARG, PPARA, PTGS1, and XDH) and anti-tussive (PPARG, PTGS1, PPARA, OPRM1, DRD2, SLC6A4, and HTR2A) effects in SB than in QB. KEGG analysis revealed that inflammation and cough, including tryptophan metabolism and arachidonic acid metabolism, were enriched in the SB group. Cellular assays revealed anti-inflammatory effects, with SB having greater effects on IL-6 and QB on TNF-α and IL-1β having overall anti-inflammatory effects. By integrating metabolomic and network analyses, the traditional classification of F. cirrhosa into SB and QB based on bulb characteristics and the observed differences are justified to a certain extent. This study provides new insights, guiding the clinical use of these treatments for inflammation and cough.