ABSTRACT
Pyroptosis, an innate immune response, plays a crucial role in the pathological process of inflammatory diseases. Although pyroptosis blockade is considered a potential therapeutic strategy, no ideal candidate drug has been identified. The natural product Chojaponilactone B (CJB) has demonstrated anti-inflammatory effects, but its role in macrophage pyroptosis has not been studied. This study aimed to investigate the effect and mechanism of CJB in inhibiting macrophage pyroptosis. Using an LPS/ATP-induced THP-1 macrophage pyroptosis model, we found that CJB significantly inhibited pyroptosis and reduced the levels of NLRP3, caspase 1, N-GSDMD, and inflammatory cytokines IL-1ß and IL-18. RNA sequencing analysis revealed that CJB interfered with LPS/ATP-induced THP-1 macrophage gene expression, suggesting involvement in anti-inflammatory and anti-pyroptotic signaling pathways. Additionally, CJB suppressed LPS/ATP-induced elevations in TLRs, MyD88, pro-IL-1ß, and NF-κB and blocked NF-κB p65 nuclear translocation. In summary, CJB inhibits NLRP3 activation and macrophage pyroptosis through the TLR/MyD88/NF-κB pathway, providing important evidence for its development as a potential drug for treating pyroptosis-related inflammatory diseases.
ABSTRACT
(+)-Sarcanan A (1a) and (-)-Sarcanan A (1b), a pair of new dihydrobenzofuran neolignan enantiomers, together with six known compounds (2-7), were isolated from the aerial parts of Sarcandra glabra. Their structures were elucidated by spectroscopic analysis, and the absolute configurations of 1a and 1b were determined by analyses of the electronic circular dichroism (ECD) data. All compounds were evaluated for their inhibitory effects on the nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW264.7 cells, and compounds 2-4 exhibited moderate inhibition against NO production.
