Pinosylvin Inhibits Inflammatory and Osteoclastogenesis via NLRP3 Inflammasome.

ABSTRACT: Pro-inflammatory cytokines such as TNF, IL-1, and IL-6 trigger aberrant osteoclastogenesis and result in massive bone loss. During RANKL-induced osteoclastogenesis, pyroptosis of macrophages/preosteoclasts acts as a pivotal mechanism for IL-1β release, thereby promoting osteoclast maturation and bone resorption. In the current study, it is observed that Pinosylvin (PIN), a compound extracted from European red pine, selectively inhibits LPS- and RANKL-induced release of IL-1β effectively reducing osteoclastogenesis. Notably, PIN inhibits the assembly of NLRP3 and the cleavage of GSDMD, pro-IL-1β, and pro-caspase-1, suggesting its therapeutic effects are NLRP3-targeted. Mechanistically, PIN blockes the NEK7/NLRP3 interaction, but not the NLRP3/ASC interaction, through its 3,5-dihydroxy group

SUBMITTER: Zhang W 

PROVIDER: S-EPMC12376636 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature