Institute of Colorectal Disease Center of Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Traditional Chinese Medicine, Nanjing 210000, China.
Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Phytomedicine. 2022 Dec;107:154455. doi: 10.1016/j.phymed.2022.154455. Epub 2022 Sep 13.
Macrophages infiltration and activation play multiple roles in maintaining intestinal homeostasis and participate in the occurrence and development of UC. Thus, the restoration of immune balance can be achieved by targeting macrophage polarization. Previous studies have reported that TXYF could effectively ameliorate DSS-induced colitis. However, the underlying mechanisms of TXYF for DSS-induced colitis are still ill-defined.
This study was designed to explore the therapeutic effect of TXYF and its regulation in macrophages polarization during DSS-induced mice. In C75BL/6 mice, dextran sulfate sodium (DSS) was used to induce colitis and concomitantly TXYF was taken orally to evaluate its curative effect. In vitro experiment was implemented on BMDMs by lipopolysaccharide, IFN- and ATP.
Here, we found that TXYF ameliorated clinical features in DSS-induced mice, decreased macrophages M1 polarization but remarkably increased M2 polarization. Mechanically, TXYF treatment effectively inhibited the activities of nuclear transcription factor NF-κB, which further contributed to the decrease of the inflammasome genes of NLRP3, limiting the activation of NLRP3 inflammasome in vivo and in vitro.
Our findings demonstrated administration of TXYF can interfere with macrophage infiltration and polarization to improve the symptoms of acute colitis, by repressing NF-κB/NLRP3 signaling pathway activation. This enriches the mechanism and provides new prospect for TXYF in the treatment of colitis.
巨噬细胞浸润和激活在维持肠道内稳态中发挥多种作用，并参与 UC 的发生和发展。因此，通过靶向巨噬细胞极化可以实现免疫平衡的恢复。先前的研究已经表明，TXYF 可以有效改善 DSS 诱导的结肠炎。然而，TXYF 治疗 DSS 诱导的结肠炎的潜在机制仍不清楚。
本研究旨在探讨 TXYF 在 DSS 诱导的小鼠中对巨噬细胞极化的调节作用及其对巨噬细胞极化的治疗效果。在 C75BL/6 小鼠中，使用葡聚糖硫酸钠（DSS）诱导结肠炎，并同时口服 TXYF 以评估其疗效。在体外实验中，使用脂多糖、IFN-和 ATP 处理 BMDMs。
我们发现，TXYF 改善了 DSS 诱导的小鼠的临床特征，减少了巨噬细胞 M1 极化，但显著增加了 M2 极化。机制上，TXYF 治疗有效地抑制了核转录因子 NF-κB 的活性，进一步导致 NLRP3 炎症小体基因的减少，限制了体内和体外 NLRP3 炎症小体的激活。
我们的研究结果表明，TXYF 的给药可以通过抑制 NF-κB/NLRP3 信号通路的激活来干扰巨噬细胞的浸润和极化，从而改善急性结肠炎的症状。这丰富了机制，并为 TXYF 在结肠炎治疗中的应用提供了新的前景。
