Volume 23 Issue 9
Sep.  2025
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ZHENG Yihao, CHEN Yue, ZHAO Kaidi, YANG Yu, MA Chongyang, ZHANG Qiuyun. The mechanistic study of tanshinone Ⅰ Regulating non-canonical pyroptosis pathway in macrophages[J]. Chinese Journal of General Practice, 2025, 23(9): 1480-1483. doi: 10.16766/j.cnki.issn.1674-4152.004159
Citation: ZHENG Yihao, CHEN Yue, ZHAO Kaidi, YANG Yu, MA Chongyang, ZHANG Qiuyun. The mechanistic study of tanshinone Ⅰ Regulating non-canonical pyroptosis pathway in macrophages[J]. Chinese Journal of General Practice, 2025, 23(9): 1480-1483. doi: 10.16766/j.cnki.issn.1674-4152.004159

The mechanistic study of tanshinone Ⅰ Regulating non-canonical pyroptosis pathway in macrophages

doi: 10.16766/j.cnki.issn.1674-4152.004159
Funds:

 82074237

  • Received Date: 2025-03-24
    Available Online: 2025-11-17
  •   Objective  To investigate the inhibitory effect and mechanism of Tanshinone Ⅰ on non-canonical pyroptosis in LPS-induced murine macrophage J774.1 cells.  Methods  A non-canonical pyroptosis model was induced in J774.1 cells by LPS transfection using Lipofecter. Cells were treated with various concentrations of Tanshinone Ⅰ, and 40 μmol/L was selected for subsequent experiments based on cytotoxicity screening. LDH release assay was used to assess cell toxicity. The expression levels of Caspase-11, GSDMD-N, NLRP3, cleaved-Caspase-1, and IL-1β were evaluated by qPCR and Western blot. Pyroptotic cells were observed by immunofluorescence. To explore the signaling pathway, the AMPK inhibitor dorsomorphin was co-administered with Tanshinone Ⅰ.  Results  Tanshinone Ⅰ at a concentration of 40 μmol/L showed no significant toxicity to J774.1 cells (P>0.05). After treatment, cell toxicity decreased from (29.540±2.123) % to (5.887±1.219) % (P=0.018). Compared with the model group, Tanshinone Ⅰ significantly inhibited the expression of Caspase-11, GSDMD-N, NLRP3, Caspase-1, cleaved-Caspase-1, and IL-1β (P < 0.05), and reduced the proportion of pyroptotic cells, indicating its ability to suppress non-canonical pyroptosis. Additionally, Tanshinone Ⅰ upregulated p-AMPK expression, whereas the AMPK inhibitor dorsomorphin reversed this effect, suggesting that its protective role may be mediated through activation of the AMPK pathway.  Conclusion  Tanshinone Ⅰ can inhibit LPS-induced non-canonical pyroptosis in J774.1 cells by activating the AMPK pathway, thereby alleviating inflammatory responses and exerting anti-inflammatory and cytoprotective effects.

     

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