Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, Dali University, Dali 671000, China.
CAS Key Laboratory of Tropical Marine Bio-Resources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China.
Molecules. 2022 Jul 10;27(14):4416. doi: 10.3390/molecules27144416.
CII-3 is the effective part of for application in oncotherapy. This study investigated its main chemical components for macrophage polarization regulation activity. Compounds were separated and purified, and their structures were elucidated based on NMR and HR-ESI-MS analyses. After inducing the M1 and M2 phenotype macrophages, CII-3 and testing components were added and co-incubated to evaluate their effects on the relevant markers of macrophages. Then, gradient concentrations of CII-3 and active monomers were further investigated for their effects on M2 macrophages. The effects were detected by RT-PCR, ELISA, flow cytometry, and immunofluorescence. Twelve compounds were identified from CII-3. CII-3 and pericanaside () had no obvious effect on M1 macrophages, while they significantly reduced the expression levels of M2 macrophage markers. Specifically, they significantly reduced the levels of TGF-β and IL-10 and the mRNA expression levels of ARG-1 and CD206 in the M2 phenotypes of RAW264.7 and Ana-1 macrophages. The conditioned medium of CII-3 and pericanaside () could inhibit the migration capacity of CT26.WT tumor cells. Macrophage M1/M2 polarization is a dynamic equilibrium, and the M2 phenotype, which can promote the growth of tumor cells, is relatively highly expressed in the tumor microenvironment. CII-3 and pericanaside could significantly reduce the phenotype of M2-type macrophages, indicating that the anti-tumor activity of CII-3 could be related to the inhibitory effect on M2 polarization, and pericanaside was one of the active components.
CII-3 是用于肿瘤治疗的有效成分。本研究调查了其对巨噬细胞极化调节活性的主要化学成分。基于 NMR 和 HR-ESI-MS 分析对化合物进行分离和纯化，并解析其结构。在诱导 M1 和 M2 表型巨噬细胞后，加入 CII-3 和测试成分并共同孵育，以评估它们对巨噬细胞相关标志物的影响。然后，进一步研究 CII-3 和活性单体的梯度浓度对 M2 巨噬细胞的影响。通过 RT-PCR、ELISA、流式细胞术和免疫荧光检测效果。从 CII-3 中鉴定出 12 种化合物。CII-3 和 peri-canaside () 对 M1 巨噬细胞没有明显作用，而它们显著降低了 M2 巨噬细胞标志物的表达水平。具体而言，它们显著降低了 RAW264.7 和 Ana-1 巨噬细胞 M2 表型中 TGF-β和 IL-10 的水平以及 ARG-1 和 CD206 的 mRNA 表达水平。CII-3 和 peri-canaside () 的条件培养基可抑制 CT26.WT 肿瘤细胞的迁移能力。巨噬细胞 M1/M2 极化是一种动态平衡，而在肿瘤微环境中，促进肿瘤细胞生长的 M2 表型相对高度表达。CII-3 和 peri-canaside 可显著降低 M2 型巨噬细胞的表型，表明 CII-3 的抗肿瘤活性可能与抑制 M2 极化有关，peri-canaside 是其活性成分之一。
