The Regulating Effect of CII-3 and Its Active Components from Periplaneta americana on M1/M2 Macrophage Polarization

Jinglei Xu; Yihao Che; Xinyue Liu; Chaohe Liu; Di Meng; Xiuqin Pang; Miao He; Guangming Liu; Chenggui Zhang; Dasong Yang; Huai Xiao

doi:10.3390/molecules27144416

The Regulating Effect of CII-3 and Its Active Components from Periplaneta americana on M1/M2 Macrophage Polarization

Molecules. 2022 Jul 10;27(14):4416. doi: 10.3390/molecules27144416.

Authors

Jinglei Xu¹, Yihao Che^{1

2

3}, Xinyue Liu^{1

4}, Chaohe Liu¹, Di Meng¹, Xiuqin Pang¹, Miao He¹, Guangming Liu¹, Chenggui Zhang¹, Dasong Yang¹, Huai Xiao¹

Affiliations

¹ Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, Dali University, Dali 671000, China.
² CAS Key Laboratory of Tropical Marine Bio-Resources and Ecology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China.
³ University of Chinese Academy of Sciences, Beijing 101408, China.
⁴ School of Pharmacy, Shanxi Medical University, Taiyuan 030001, China.

Abstract

CII-3 is the effective part of Periplaneta americana 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 (5) 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 (5) 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.

Keywords: M2 macrophages; Periplaneta americana; chemical components; pericanaside (5).

MeSH terms

Animals
Biomarkers / metabolism
Macrophage Activation
Macrophages
Periplaneta*
Phenotype

Substances

Biomarkers

Grants and funding

This work was financially supported by a grant from the National Natural Science Foundation of China (No. 82160822, 81960755, 81860742, 81860765, 81903926), the Special Program of Science and Technology of Yunnan Province (202002AA100007), and the Special Fund Project for the Development of TCM Decoction Pieces Industry of Yunnan Province (2019-YG-067).