Inflammatory suppression and immunity regulation benefits of honokiol in a rat model of acute peritonitis via the regulation of NLRP3 inflammasome and Sirt1/autophagy axis

• Ximing Pan ^[1] ; Zhou Hua ^[1] ; Guocai Fan ^[1] ; Qinglong Feng ^[2]
  1. [1] Suichang People’s Hospital, Lishui, PR China
  2. [2] Quzhou Kecheng People’s Hospital, Quzhou, PR China
• Localización: Histology and histopathology: cellular and molecular biology, ISSN-e 1699-5848, ISSN 0213-3911, Vol. 39, Nº. 7, 2024, págs. 921-934
• Idioma: inglés
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• Resumen

  • Background. NLRP3 inflammasome and Sirt1/autophagy axis are potential targets for advancing acute peritonitis (AP). Honokiol (HNK), a bioactive substance, has the potential to improve AP.

    Materials and methods. The AP model rats were established by cecal ligation and puncture (CLP). Rats were randomized into the Sham, Sham+HNK, CLP, and CLP+HNK groups. The therapeutic effects of HNK on organ infection, inflammation and immunity were observed in AP rats. The inflammation of RAW 264.7 cells was induced by lipopolysaccharide (LPS) and divided into the Control, HNK, LPS, and LPS+HNK groups. The effects of HNK on immunity and inflammation were observed. Moreover, the inflammatory cell model was further transfected with NLRP3 overexpressing plasmid, and the regulatory effect of HNK on NLRP3 in AP cells was detected.

    Results. HNK treatment improved survival, biochemical indexes, and lung and kidney injury and inhibited inflammatory cytokine release and bacterial infection in CLP rats. In CLP rats and RAW 264.7 cells, HNK treatment improved the release of the CD4+ and CD8+ T cells, decreased the associated proteins’ levels of the NLRP3 inflammasome, and activated the expression of proteins in the Sirt1/autophagy axis. It improved viability and reduced apoptosis and the degrees of TNF-α, IL-1β, and IL-6 mRNA in RAW 264.7 cells. In addition, HNK treatment antagonized the effect of NLRP3-overexpressed on inflammation and immunity.

    Conclusions. HNK improved AP by inhibiting NLRP3 inflammasome and activating the Sirt1 autophagy axis in vivo and in vitro.