Rosthornin B alleviates inflammatory diseases via directly targeting NLRP3.

ABSTRACT: Aberrant activation of the NLRP3 inflammasome contributes to the evolution of diverse inflammatory diseases. Inhibition of the NLRP3 inflammasome has been proven to be an effective treatment strategy for NLRP3-driven diseases. This study revealed that multiple natural diterpenes from Isodon plants can inhibit the NLRP3 inflammasome, among which Rosthornin B (Ros B) exhibited the best inhibitory effect, with an IC₅₀ of 0.39 μM. Further study revealed that Ros B directly interacts with NLRP3, thereby restraining NEK7-NLRP3 interaction and inhibiting NLRP3 inflammasome assembly and activation. Remarkably, Ros B had a significant therapeutic benefit in mouse models of NLRP3-driven septic shock, peritonitis, and colitis. Our study has identified a series of natural diterpenes that ta

SUBMITTER: Yang Y 

PROVIDER: S-EPMC11646051 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature