Arctigenin, the major active constituent of Fructus Arctii, has been reported to inhibit the growth of various tumors and alleviate colitis. This study aimed to prove the protective effect of arctigenin on colitis-associated cancer (CAC) and explore its mechanisms. Orally administered arctigenin prevented the progression of colitis and protected against colon carcinogenesis in azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CAC mice. Arctigenin downregulated NLRP3 inflammasome activation and fatty acid oxidation (FAO) metabolism in macrophages, as determined by untargeted metabolomics. Arctigenin also inhibited the expression of carnitine palmitoyltransferase 1 (CPT1), reduced the acetylation of α-tubulin, and disrupted NLRP3 complex formation, which in turn inactivated the NLRP3 inflammasome. Downregulation of the CPT1-FAO-acetyl-coenzyme A (acetyl-CoA)-acetylated α-tubulin pathway was observed to inhibit the effect of arctigenin on NLRP3 inflammasome assembly, as confirmed by CPT1 overexpression. Lastly, arctigenin was shown to inhibit NLRP3 inflammasome activation and improve CAC in mice, and the effect was significantly diminished by the overexpression of adeno-associated virus (AAV)9-CPT1. Taken together, these results show that the inhibition of NLRP3 inflammasome assembly in macrophages due to FAO downregulation contributes to the preventative effect of arctigenin against CAC. Our findings highlight the potential value of arctigenin to reduce the risk of CAC in patients with colitis.

据报道，Arctigenin是Arc果的主要活性成分，可抑制各种肿瘤的生长并减轻结肠炎。这项研究旨在证明Arctigenin对结肠炎相关癌症（CAC）的保护作用，并探讨其机制。口服给予的arctigenin可预防由乙氧基甲烷（AOM）/右旋糖酐硫酸钠（DSS）诱导的CAC小鼠结肠炎的发展并防止结肠癌的发生。根据未定目标的代谢组学研究，Arctigenin下调了巨噬细胞中的NLRP3炎性小体激活和脂肪酸氧化（FAO）代谢。Arctigenin还抑制肉碱棕榈酰转移酶1（CPT1）的表达，减少α-微管蛋白的乙酰化，并破坏NLRP3复合物的形成，进而使NLRP3炎性体失活。如CPT1过表达所证实，观察到CPT1-FAO-乙酰辅酶A（乙酰-CoA）-乙酰化的α-微管蛋白途径的下调抑制了Arctigenin对NLRP3炎症小体组装的作用。最后，显示arctigenin可抑制小鼠中的NLRP3炎性体活化并改善CAC，并且腺相关病毒（AAV）9-CPT1的过表达显着降低了这种作用。综上所述，这些结果表明，由于粮农组织的下调，巨噬细胞对NLRP3炎性小体组装的抑制作用有助于Arctigenin对CAC的预防作用。我们的发现凸显了Arctigenin降低结肠炎患者CAC风险的潜在价值。如CPT1过表达所确认。最后，显示arctigenin可抑制小鼠中的NLRP3炎性体活化并改善CAC，并且腺相关病毒（AAV）9-CPT1的过表达显着降低了这种作用。综上所述，这些结果表明，由于粮农组织的下调，巨噬细胞对NLRP3炎性小体组装的抑制作用有助于Arctigenin对CAC的预防作用。我们的发现凸显了Arctigenin降低结肠炎患者CAC风险的潜在价值。如CPT1过表达所确认。最后，显示arctigenin可抑制小鼠中的NLRP3炎性体活化并改善CAC，并且腺相关病毒（AAV）9-CPT1的过表达显着降低了这种作用。综上所述，这些结果表明，由于粮农组织的下调，巨噬细胞对NLRP3炎性小体组装的抑制作用有助于Arctigenin对CAC的预防作用。我们的发现凸显了Arctigenin降低结肠炎患者CAC风险的潜在价值。这些结果表明，由于FAO的下调，巨噬细胞对NLRP3炎性体装配的抑制作用有助于arctigenin对CAC的预防作用。我们的发现凸显了Arctigenin降低结肠炎患者CAC风险的潜在价值。这些结果表明，由于FAO的下调，巨噬细胞对NLRP3炎性体装配的抑制作用有助于arctigenin对CAC的预防作用。我们的发现凸显了Arctigenin降低结肠炎患者CAC风险的潜在价值。