Schisandrin B prevents PM2.5-induced pyroptosis by protecting cell membrane integrity

Abstract

Abstract The main active substances of Schisandra chinensis are lignans. Lignans are largely composed of schisandrin B (Sch B), which has a very high biphenyl cyclooctene content. This study was designed to evaluate the ability of Sch B to repair the particulate matter 2.5 (PM2.5)-induced THP-1 cell injury and determine the underlying mechanism of Sch B action. The results showed that Sch B significantly inhibited interleukin-1ꞵ (IL-1ꞵ) secretion and reduced PM2.5-caused cell pyroptosis. Mechanistically, Sch B reduced both cell membrane damage and the release of inflammatory factors via active reduction of caspase-1 enzyme activity and subsequent inhibition of gasdermin D (GSDMD) cleavage to N-GSDMD. In addition, Sch B treatment promoted the transcription of ALG2, ALIX, TSG101, and CHMP4B and membrane repair via ESCRT-III. Thus, we demonstrated that Sch B, the main active component of S. chinensis extracts, has anti-PM2.5 effect and elucidated the underlying mechanism of Sch B effects against THP-1 cell pyroptosis.