110: SO-HW01, a medicinal plant extract, inhibits inflammasome activation and prevents endotoxin-induced septic shock in mice

Abstract

Inflammasome is known as a cytosolic protein complex of nucleotide-binding domain and leucine rich repeat containing protein (NLRs) or AIM2, ASC and caspase-1 and assembled in response to the detection of endogenous and pathogen-associated danger signals. Activated caspase-1 mediates the proteolytic maturation of interleukin-1β (IL-1β), which plays an important role in innate immune responses. However, dysregulated production of IL-1β is associated with a number of autoinflammatory disorders and its inhibition has been proved to be beneficial in the treatment of these diseases. The purpose of this study was to screen inflammasome inhibitors from medicinal herbal extracts. We identified that SO-HW01 possessed an inhibitory effect on inflammasome induction. SO-HW01 effectively suppressed IL-1β production triggered by ATP or nigericin or Listeria monocytogenes, which induce NLRP3 inflammasome, Salmonella thyphimurium, which involve NLRC4, and dsDNA, which active AIM2, in a dose dependent manner. The mechanism of action of SO-HW01 was related to the inhibition of the cleavage of pro-caspase-1 and pro-IL-1β which in turn suppressed the activation of inflammasome. SO-HW01 significantly reduced LPS-induced septic shock by inhibiting production of IL-1β and IL-18. Taken together, our results demonstrate that HSO inhibits NLRP3, NLRC4, and AIM2 inflammasome activation and it has a potential use in the treatment of inflammsome-mediated diseases.