Cepharanthine protects against lipopolysaccharide-induced acute lung injury in mice by blocking NLRP3 inflammasome activation.

Abstract

Acute lung injury (ALI) is a common life-threatening lung disease with high mortality and is mostly related to acute inflammatory responses in the lungs. Cepharanthine (CEP), a natural compound extracted from Stefania's genus, has anti-inflammatory and antioxidant properties. However, whether CEP has a protective effect on ALI and its potential mechanism of action are unclear. This study investigated the therapeutic effects and mechanisms of CEP on LPS-induced ALI in mice and related cellular models. CEP alleviated pulmonary inflammation in ALI mice, significantly reducing TNF-α and IL-1β levels in the serum and bronchoalveolar lavage fluid (BALF). CEP inhibited LPS-induced inflammatory responses in MH-S macrophages, as evidenced by reduced proinflammatory cytokine secretion and downregulated NF-κB/NLRP3 signaling. Mechanistically, CEP suppressed the activation of the NF-κB/NLRP3 inflammasome pathway both in vivo and in vitro. Furthermore, CEP attenuated LPS-induced MLE-12 apoptosis, decreasing the expression of apoptosis-related proteins. The protective effects on MLE-12 cells were associated with the inhibition of the NF-κB/NLRP3 pathway. Molecular docking and SPR studies indicated that CEP potentially binds to NLRP3, suggesting a direct interaction. Collectively, these findings demonstrate that CEP mitigates ALI by modulating NF-κB/NLRP3 signaling, suppressing inflammation, and reducing apoptosis, highlighting its potential as a therapeutic candidate for ALI.