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Peer-reviewed veterinary case report

Cepharanthine mitigates NIBV-induced pyroptosis via the MDA5/NF-κB/NLRP3 signaling pathway.

Journal:
Veterinary microbiology
Year:
2025
Authors:
Liu, Zhenni et al.
Affiliation:
College of Animal Science and Technology · China

Abstract

This study elucidates the mechanism through which cepharanthine (CEP) mitigates NIBV-induced pyrodeath in renal tubular epithelial cells by modulating the MDA5/NF-&#x3ba;B/NLRP3 signaling pathway. Primary renal tubular epithelial cells (RTECs) were isolated from one-day-old Hy-Line Brown chicks and subsequently assigned to four groups. The C+CEP and N&#x202f;+&#x202f;CEP groups received 0.5&#x202f;&#x3bc;M CEP, while the NIBV and N&#x202f;+&#x202f;CEP groups were exposed to 1 MOI of the SX9 strain of NIBV. The study shows that CEP significantly reduces NIBV load (P&#x202f;<&#x202f;0.05) and decreases the mRNA and protein levels of MDA5/NF-&#x3ba;B/NLRP3 signaling components, such as MDA5, ISP-1, TRAF6, TAK1, NF-&#x3ba;B, IKK&#x3b1;, IKK&#x3b2;, NLRP3, caspase-1, IL-1&#x3b2;, and IL-18, upon NIBV infection (P&#x202f;<&#x202f;0.05 or P&#x202f;<&#x202f;0.01). Moreover, CEP markedly reduced cellular pyroptosis (P&#x202f;<&#x202f;0.001) and lactate dehydrogenase (LDH) activity (P&#x202f;<&#x202f;0.01). Flow cytometry and fluorescence-based assays corroborated these findings, revealing a substantial diminution in pyroptosis post-NIBV infection in CEP-treated cells (P&#x202f;<&#x202f;0.01). Laser confocal microscopy revealed a clear decrease in NLRP3-associated red fluorescence foci after CEP treatment. These results highlight that CEP could mitigate NIBV-induced pyroptosis in RTECs by modulating the MDA5/NF-&#x3ba;B/NLRP3 signaling pathway.

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Original publication: https://pubmed.ncbi.nlm.nih.gov/40273551/