Systematic investigation of the material basis, multiple mechanisms and quality control of Simiao Yong'an decoction combined with antibiotic in the treatment of sepsis

•SMYAD specialized for septic symptoms of heat, poison and blood stasis in TCM theory.•SMYAD united antibiotics alleviated sepsis-induced multiple organ dysfunction.•Six compounds and 8 metabolites were revealed as Q-markers and biomarkers of SMYAD.•Multi-mechanisms were anti-inflammation, improving coagulation and microcirculation. Sepsis is one of the major threats to human health with high mortality. Simiao Yong'an decoction (SMYAD) has the efficacy of anti-inflammation, improving coagulation and microcirculation, which is applicable for the clinical assistance treatment of sepsis. Yet, its material basis and relevant mechanisms are still vague. Explore the quality markers (Q-markers), biomarkers and potential mechanisms of SMYAD combined with imipenem/cilastatin sodium for anti-sepsis. Linear-Trap-LC/MSn was employed to profile the compounds in the extract and medicated serum of SMYAD. Then, the components and targets obtained from databases were applied to network pharmacology. Q-markers’ range was narrowed via the affinity of three times docking and determined as per its screening criteria. Also, the content of them was detected by HPLC. Next, cecal ligation and puncture (CLP) model was reproduced to observe the effect of SMYAD united antibiotic by survival rate, histopathology score, ELISA, western blot and qPCR. Finally, metabolomics based upon GC–MS was exerted to discover the differential endogenous metabolites, metabolic pathway and joint pathway of SMYAD combined with antibiotic for sepsis. The 25 serum migrant ingredients derived from 113 chemical compounds of SMYAD were identified for the first time, and 6 components were determined as the Q-markers of SMYAD. The enrichment analysis indicated that the potential mechanism was mainly associated with the IL-17 signaling pathway, complement-coagulation cascades signaling pathway and VEGF signaling pathway. Then, SMYAD united antibiotic declined the mortality of septic rats, restored cytokine levels, ameliorated histopathological lesions and decreased the mRNA and protein expression of target proteins in a dose-dependent way. Furthermore, 8 differential metabolites were regarded as latent biomarkers related to the antiseptic effect of SMYAD united antibiotic, which were mainly involved in the Citrate cycle (TCA cycle) metabolic pathway. Different skeletons of compounds, including iridoids, phenylpropanoids, organic acids, triterpenes and others, were the main compositions of SMYAD. Among them, 6 c