Huang Qin decoction (HQD) is a traditional Chinese medicine formula for treating colitis, but the effects and molecular mechanism of action of HQD in colitis-associated carcinogenesis (CAC) are still unclear. Therefore, we aimed to determine the beneficial effects of HQD on CAC in mice and to reveal the underlying mechanism involved. AOM/DSS was used to induce CAC in mice, and the effects of HQD on tumorigenesis in mice were examined (with mesalazine serving as a positive control). Mesalazine or HQD treatment alleviated body weight loss and decreased the disease activity index in mice induced by AOM/DSS. Mesalazine or HQD treatment also suppressed the shortening of colon tissue length, the number of tumors, and the infiltration of inflammatory cells. The genes targeted by HQD were predicted and verified, followed by knockout experiments. Elevated SLC6A4 and inhibited serotonin production and inflammation were observed in HQD-treated mice. HQD inhibited the NFκB and NLRP3/caspase1/GSDMD pathways. The therapeutic effect of HQD was diminished in SLC6A4-deficient AOM/DSS mice. Additionally, the downregulation of SLC6A4 mitigated the inhibitory effect of HQD-containing serum on MODE-K cell pyroptosis. Our findings suggest that SLC6A4 is a pivotal regulator of HQD-alleviated CAC via its modulation of the NLRP3/caspase1/GSDMD pathway.

黄芩汤（HQD）是治疗结肠炎的中药方剂，但HQD在结肠炎相关癌变（CAC）中的作用和分子机制尚不清楚。因此，我们的目的是确定 HQD 对小鼠 CAC 的有益作用并揭示其潜在机制。采用AOM/DSS诱导小鼠CAC，并考察HQD对小鼠肿瘤发生的影响（以美沙拉嗪作为阳性对照）。美沙拉嗪或 HQD 治疗减轻了 AOM/DSS 诱导的小鼠体重减轻并降低了疾病活动指数。美沙拉嗪或 HQD 治疗还抑制了结肠组织长度的缩短、肿瘤的数量和炎症细胞的浸润。对HQD靶向的基因进行了预测和验证，然后进行了敲除实验。在 HQD 治疗的小鼠中观察到 SLC6A4 升高并抑制血清素产生和炎症。HQD 抑制 NFκB 和 NLRP3/caspase1/GSDMD 通路。HQD 的治疗效果在 SLC6A4 缺陷的 AOM/DSS 小鼠中减弱。此外，SLC6A4的下调减轻了含HQD的血清对MODE-K细胞焦亡的抑制作用。我们的研究结果表明，SLC6A4 通过调节 NLRP3/caspase1/GSDMD 通路，成为 HQD 减轻的 CAC 的关键调节因子。