The multi-target capabilities of the compounds in a TCM used to treat sepsis and their in silico pharmacology

SummaryObjectiveThis study aims to explain the mechanisms at the molecular level of a traditional Chinese medicine (TCM) for the treatment of sepsis.MethodsWe first identified 16 targets involved in the sepsis disease network; then we constructed a molecular ligand database and investigated the effects between the ligand database and the sepsis targets using computational biology methods. The results of the calculation were validated with in vitro biological testing against bovine thrombin.Results and conclusionWe found that multiple active compounds contained in the TCM interact with multiple sepsis-related targets. We predicted several promising compounds for sepsis treatment, and the first 10 compounds were characterised. Among those tested, rosmarinic acid displayed the strongest biological activity in the in vitro activity test with a half-maximal inhibitory concentration (IC50) of 85 μM. This study demonstrates a novel way of identifying naturally occurring chemical entities as new leads for sepsis treatment.