Green Tea Extract Improves Cyclophosphamide-Induced Immunosuppression in Mice and Enhances the Immune Activity of Raw 264.7 Cells

Abstract

Cyclophosphamide (CP) is mainly used for the treatment of autoimmune diseases and cancer; however, it damages normal immune cells. Therefore, the effects of clinical chemotherapy of CP are limited. Green tea has been reported to effectively modulate immune functions. In the present study, in view of the pharmacological properties of green tea, we evaluated the properties of green tea extract (GTE) to enhance CP-induced immunosuppression in vivo and to activate macrophages in vitro. GTE significantly improved the suppressed immune function, including the spleen index and proliferation of spleen T lymphocytes, as revealed by histopathological examination and flow cytometry analysis. In addition, GTE effectively activated RAW 264.7 cells, as represented by the induction of nitric oxide, reactive oxygen species, and cytokine levels. GTE also elevated phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B in RAW 264.7 cell. In conclusion, GTE ameliorated CP-induced immunosuppression in mice and stimulated immune activity in RAW 264.7 cells, possibly by activating the MAPKs signaling pathway. These findings suggest that GTE has the potential to be used as a supplementary agent in CP chemotherapy.

Note:

Funding Information: This work was supported by the research fund of Chungnam National University and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2021R1A6A1A03045495). This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (2021R1A4A1033078).

Declaration of Interests: The authors declare no conflict of interest

Ethical Approval Statement: The animal experimental protocol was approved by the Institutional Animal Care and Use Committee of the Chungnam National University (202112A-CNU-191).

Keywords: Green tea extract, Cyclophosphamide, Immunosuppression, macrophage, Mitogen-activated protein kinases, Nuclear factor kappa B