A hot‐water extract of Sanguisorba officinalis ameliorates endotoxin‐induced septic shock by inhibiting inflammasome activation

ABSTRACT The inflammasome is a multiprotein signaling complex that mediates inflammatory innate immune responses through caspase 1 activation and subsequent IL‐1β secretion. However, because its aberrant activation often leads to inflammatory diseases, targeting the inflammasome holds promise for the treatment of inflammation‐related diseases. In this study, it was found that a hot‐water extract of Sanguisorba officinalis (HSO) suppresses inflammasome activation triggered by adenosine 5′‐triphosphate, nigericin, microbial pathogens, and double stranded DNA in bone marrow‐derived macrophages. HSO was found to significantly suppress IL‐1β production in a dose‐dependent manner; this effect correlated well with small amounts of caspase 1 and little ASC pyroptosome formation in HSO‐treated cells. The anti‐inflammatory activity of HSO was further confirmed in a mouse model of endotoxin‐induced septic shock. Oral administration of HSO reduced IL‐1β titers in the serum and peritoneal cavity, increasing the survival rate. Taken together, our results suggest that HSO is an inhibits inflammasome activation through nucleotide‐binding domain and leucine‐rich repeat pyrin domain 3, nucleotide‐binding domain and leucine‐rich repeat caspase recruitment domain 4 and absent in melanoma 2 pathways, and may be useful for treatment of inflammasome‐mediated diseases.