结直肠癌（CRC）转移是一个复杂的过程，不仅涉及肿瘤细胞，而且肿瘤微环境（TME）的关键组成部分M2型肿瘤相关巨噬细胞的作用在癌症转移中发挥着至关重要的作用。肉豆蔻木脂素是从肉豆蔻中分离出来的一种口服活性木脂素，具有多种有益的生物活性，包括抗癌作用，但其对 TME 中巨噬细胞极化的影响仍不清楚。 评估肉豆蔻木脂素对巨噬细胞 M2 极化的抑制效力和前瞻性机制采用蛋白质印迹、流式细胞术、免疫荧光和网络药理学等方法测定肉豆蔻木脂素调节M1和M2型巨噬细胞的极化及具体机制。通过体外和体内功能测定来研究肉豆蔻衣木脂素在 CRC 转移中的作用。肉豆蔻衣木脂素通过抑制活性氧 (ROS) 依赖性的 PI3K/AKT 通路，有效抑制 IL-4/13 诱导的 M2 巨噬细胞极化。方式。 CRC肝转移患者的CD206 M2巨噬细胞比例升高。此外，肉豆蔻木脂素在体外和体内抑制 M2 巨噬细胞介导的 CRC 细胞转移。从机制上讲，Macelignan减少了M2巨噬细胞分泌IL-1β，进而阻断NF-κB p65核转位并抑制转移。Macelignan通过ROS介导的PI3K/AKT信号通路抑制巨噬细胞M2极化，从而阻止IL-1β/NF- κB依赖性CRC转移。在本研究中，我们揭示了肉豆蔻木脂素在预防 CRC 转移方面先前未被认识的机制，并证明了其在 CRC 治疗中有效且安全的治疗潜力。版权所有 © 2023 Elsevier GmbH。版权所有。

Colorectal cancer (CRC) metastasis is a complicated process that not only involves tumor cells but also the effects of M2 type tumor-associated macrophages, a key component of the tumor microenvironment (TME), act a crucial role in cancer metastasis. Macelignan, an orally active lignan isolated from Myristica fragrans, possesses various beneficial biological activities, including anti-cancer effects, but its effect on macrophage polarization in the TME remains unknown.To evaluate the inhibitory potency and prospective mechanism of macelignan on M2 polarization of macrophages and CRC metastasis.The polarization and specific mechanism of M1 and M2 macrophage regulated by macelignan were determined by western blot, flow cytometry, immunofluorescence and network pharmacology. In vitro and in vivo function assays were performed to investigate the roles of macelignan in CRC metastasis.Macelignan efficiently inhibited IL-4/13-induced polarization of M2 macrophages by suppressing the PI3K/AKT pathway in a reactive oxygen species (ROS)-dependent manner. The proportion of CD206+ M2 macrophages was elevated in patients with CRC liver metastasis. Furthermore, macelignan inhibited M2 macrophage-mediated metastasis of CRC cells in vitro and in vivo. Mechanistically, macelignan reduced secretion of IL-1β from M2 macrophages, which in turn blocked NF-κB p65 nuclear translocation and inhibited metastasis.Macelignan suppressed macrophage M2 polarization via ROS-mediated PI3K/AKT signaling pathway, thus preventing IL-1β/NF-κB-dependent CRC metastasis. In the present study, we reveal a previously unrecognized mechanism of macelignan in the prevention of CRC metastasis and demonstrate its effectively and safely therapeutic potential in CRC treatment.Copyright © 2023 Elsevier GmbH. All rights reserved.