An integrated network pharmacology and metabolomics approach reveals the mechanism of action of Andrographis paniculata and Senecio scandens in ameliorating dextran sulfate sodium-induced ulcerative colitis in mice

The herb pair of Andrographis paniculata and Senecio scandens (APSS) is commonly used in traditional Chinese medicine to treat ulcerative colitis (UC). This study explored the therapeutic efficacy and underlying mechanism of APSS in UC treatment through in vivo experiments using dextran sulfate sodium (DSS)-induced colitis mice models. While AP, SS, and APSS all alleviated colitis to some extent, APSS demonstrated superior therapeutic effects compared to those of the individual herbs. Subsequently, network pharmacological analysis identified tumor necrosis factor and nuclear factor kappa B (NF-κB) as the key potential targets of APSS action. Metabolomic analysis revealed that APSS regulates metabolic pathways, such as arachidonic acid (AA) metabolism and the tricarboxylic acid cycle. Notably, APSS restored levels of organic acids (e.g., pyruvic acid and succinic acid), fatty acyls (e.g., leukotriene A4 and 8,9-epoxyeicosatrienoic acid), and fatty acids (e.g., palmitic acid and oleic acid). The combined analysis of network pharmacology and metabolomics identified AA metabolic pathways as the most important pathways in the role of APSS in treating UC. Furthermore, the APSS-treated group exhibited decreased expression of phosphorylated NF-κB p65, and NOD-like receptor 3 (NLRP3), suggesting that APSS inhibited the NF-κB/NLRP3 inflammasome pathway. Meanwhile, 16S rRNA analysis showed that the APSS treatment rebalanced the levels of gut bacteria, such as Lactobacillus , Lactococcus , Enterococcus , and Klebsiella , and elevated short-chain fatty acid levels. Overall, the study suggests that APSS alleviates UC by inhibiting the NF-κB/NLRP3 pathway and modulating metabolites and gut microbiota. Thus, APSS action helps improve intestinal homeostasis and provides a potential therapeutic option for UC. • Herb pair of Andrographis paniculata and Senecio scandens (APSS) was studied. • APSS treatment alleviated ulcerative colitis. • APSS regulates key metabolic pathways and restores metabolites. • APSS inhibited the nuclear factor kappa B and NLRP3 inflammasome pathways. • APSS altered gut microbiota composition and increased short-chain fatty acids.