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. 2024 Jul 26;15:1388753. doi: 10.3389/fphar.2024.1388753

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Copyright © 2024 Lin, Dai, Zhang and Xu.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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WWXDD reduced the expression of NLRP3-mediated inflammatory pathways. (A) The mRNA expression of NLRP3 in the model group (1.53 ± 0.097) was significantly higher than that in the control group (1 ± 0.11), and the expression of NLRP3 in the WWXDD medium-dose (1.07± 0.20), high-dose (0.95 ± 0.15), and colchicine groups (0.92 ± 0.11) showed a significant decrease (p < 0.01). (B) Caspase-1 mRNA expression in the model group (7.48 ± 0.53) was significantly higher than that in the control group (1.00 ± 0.37). However, there was a significant decrease in caspase-1 expression observed in the WWXDD low-dose (3.27 ± 0.24), medium-dose (3.21 ± 0.16), high-dose (4.66 ± 0.06) and colchicine group (2.41 ± 0.27) compared to the model group (p < 0.01). (C) Pro-IL-1β mRNA expression levels were significantly elevated in the model group (1.96 ± 0.14) compared to those of control group (1.0 ± 0.13). Conversely, treatment with WWXDD at low dose (0.82 ± 0.36), medium-dose (0.70 ± 0.19), high-dose (0.63 ± 0.19) or colchicine (0.50 ± 0.17) resulted in a significant reduction of pro-IL-lβ gene expression (p < 0.01). (D) The mRNA expression level of IL-lβ was markedly increased in the model group (1.70 ± 0.14) as compared to that of control group (1.0 ± 0.46). In contrast, administration of WWXDD at low dose low-dose (0.70 ± 0.28), medium-dose (0.42 ± 0.21), high-dose (0.76 ± 0.34), or colchicine (0.60 ± 0.26) led to a substantial decrease m IL-lβ gene expression (P < 0.01). (E) Western blot analysis revealed distinct bands for NLRP3, Caspase-I, and IL-l β proteins following treatment with WWXDD. (F–H) Quantitative analysis demonstrated reduced protein expressions for NLRP3, caspase-I, and IL-l β after administration of WWXDD (p < 0.01). NC, normal control group; Model, model group; Low, low dose WWXDD group; Medium, medium dose WWXDD group; High, high dose WWXDD group; Colchicine, positive control group. All data were shown as mean ± SEM. Results are derived from 3 separate experiments. **p < 0.01, ***p < 0.001, ****p <0.0001.