In silico analysis based on constituents of the medicinal plant Xuebijing (XBJ) to identify candidate treatment agents for sepsis in the omics-driven research era

BACKGROUND: Sepsis is the most common cause of mortality in intensive care units. The activation of toll-like receptor 4 (TLR4) and its recognition by myeloid differentiation 2 (MD-2) amplify a cascade of cytokinin production responsible for the inflammation in sepsis.METHODS: We designed a drug discovery study screening for sepsis treatments that included network analysis and prediction of protein-protein interactions (PPIs), molecular docking and possible toxicity evaluation. We identified the phytoconstituents of Xuebijing (XBJ) in the literature and tabulated them to construct a network analysis and identify all the bioactive agents according to their organic class.RESULTS: Our molecular docking analysis showed strong binding energies for cryptotanshinone and tanshinone IIA (docking scores for MD-2 of -9.3 and -9.2 kcal/mol, respectively). We identified MD-2 as a target of the potent bioactive component cryptotanshinone confirming a possible inhibitory effect against the cytokine response causing sepsis.CONCLUSIONS: Our findings suggest that the phytoconstituent cryptotanshinone may inhibit the inflammatory cascade in sepsis and should be studied as a candidate treatment against sepsis-like diseases.