Schisandrin B Attenuates PM_2.5-Induced Pyroptosis via Caspase-1 Inhibition and Membrane Repair

Schisandra chinensis (Turcz.) Baill. (Schisandraceae) is a medicinal plant widely distributed in East Asia and has long been used in traditional herbal medicine. Phytochemical studies have identified lignans as the major bioactive constituents of S. chinensis, among which Schisandrin B (Sch B) is one of the most abundant and pharmacologically active compounds. Previous studies have demonstrated that Sch B exhibits a variety of biological activities, including antioxidant, anti-inflammatory, hepatoprotective, and cytoprotective effects. As a natural lignan compound derived from S. chinensis, Sch B has attracted increasing attention for its potential protective effects against environmental and inflammatory insults. This study aimed to investigate the protective effects of Sch B against PM_2.5-induced inflammatory injury in THP-1 cells and to elucidate the underlying molecular mechanisms. An in vitro PM_2.5-induced THP-1 cell injury model was established by stimulating THP-1 cells with PM_2.5. Subsequently, Sch B was applied to the model, and inflammation-related indicators and pathways were detected using methods such as ELISA, PCR, and Western Blot (WB). The results showed that Sch B significantly inhibited interleukin-1β (IL-1β) secretion and attenuated PM_2.5-induced pyroptosis in THP-1 cells. Mechanistically, Sch B alleviated cell membrane damage and inflammatory factor release by suppressing Caspase-1 activation and inhibiting the cleavage of gasdermin D (GSDMD) into its active N-terminal fragment (N-GSDMD). Furthermore, Sch B treatment was associated with the up-regulation of ALG-2, ALIX, and TSG101, suggesting the potential involvement of ESCRT-III-associated membrane repair mechanisms. In conclusion, Sch B, a natural lignan compound derived from S. chinensis, exhibits protective effects against PM_2.5-induced THP-1 cell pyroptosis by reducing cell membrane damage and inflammatory cytokine release. These effects are associated with the inhibition of Caspase-1 activity and GSDMD cleavage, as well as the activation of ESCRT-III-associated membrane repair responses. Collectively, these findings highlight the potential of Sch B as a natural cytoprotective compound against particulate matter-induced inflammatory injury.