Elucidating the integrative role and possible molecular mechanisms of Salvia miltiorrhiza ingredients and gut microbiota-derived metabolites in alleviating pyroptosis-mediated hepatic ischemia-reperfusion injury through network pharmacology.

Currently, therapeutic options for hepatic ischemia-reperfusion injury (HIRI) remain limited and challenging. An emerging alternative involves the combination of ingredients from traditional Chinese medicine (TCM) and beneficial gut microbiota (GM) metabolites. This study integrates ingredients of Salvia miltiorrhiza (SM) and metabolites of GM to assess their combined therapeutic efficacy against HIRI through pyroptosis using network pharmacology. Twenty-nine final targets were recognized as key proteins responsible for the alleviation of HIRI by SM ingredients and GM metabolites through pyroptosis, with GAPDH, AKT1, ILB1 emerging as central targets in the protein-protein interaction (PPI) network. The Toll-like receptor (TLR), NOD-like receptor (NLR), IL-17, TNF and MAPK signalling pathways were identified as key pathways in the therapeutic effects of SM ingredients and GM metabolites. Eight microRNAs (miRNAs) were predicted to be potential miRNAs exerting the most influence. Four SM ingredients and 11 GM metabolites were identified as non-toxic, promising candidates against HIRI. Moreover, the results of molecular docking showed all compounds were well combined with the corresponding proteins. This study highlights the therapeutic potential of TCM and beneficial GM in HIRI treatment and provides a foundational dataset for future research on their combined application. Further in vitro and in vivo studies are needed to validate these findings.