Green tea EGCG inhibits naïve CD4+ T cell division and progression in mice: An integration of network pharmacology, molecular docking and experimental validation

Xinli Niu; Zejin Liu; Junpeng Wang; Dayong Wu

doi:10.1016/j.crfs.2023.100537

Green tea EGCG inhibits naïve CD4⁺ T cell division and progression in mice: An integration of network pharmacology, molecular docking and experimental validation

Curr Res Food Sci. 2023 Jun 18:7:100537. doi: 10.1016/j.crfs.2023.100537. eCollection 2023.

Authors

Xinli Niu^{1

2

3}, Zejin Liu¹, Junpeng Wang^{1

3}, Dayong Wu³

Affiliations

¹ Translational Medical Center, Huaihe Hospital of Henan University, Kaifeng, 475000, China.
² College of Life Science, Henan University, Kaifeng, 475000, China.
³ Nutritional Immunology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, 02111, USA.

Abstract

Dietary green tea epigallocatechin-3-gallate (EGCG) could attenuate experimental autoimmune encephalomyelitis via the modification of the balance of CD4⁺ T helper (Th) cells. Moreover, EGCG administration in vitro has a direct impact on the regulatory cytokines and differentiation of CD4⁺ T cells. Here, we aim to determine whether EGCG directly affects the cell division and progression in naive CD4⁺ T cells. We first investigate the effect of EGCG on naïve CD4⁺ T cell division and progression in vitro. An integrated analysis of network pharmacology and molecular docking was utilized to further identify the targets of EGCG for T cell-mediated autoimmune diseases and multiple sclerosis (MS). EGCG treatment prevented naïve CD4⁺ T cells from progressing through the cell cycle when stimulated with anti-CD3/CD28 antibodies. This was achieved by increasing the proportion of cells arrested in the G0/G1 phase by 8.6% and reducing DNA synthesis activity by 51% in the S phase. Furthermore, EGCG treatment inhibited the expression of cyclins (cyclin D1, cyclin D3, cyclin A, and cyclin B1) and CDKs (CDK2 and CDK6) during naïve CD4⁺ T cell activation in response to anti-CD3/CD28 stimulation. However, EGCG inhibited the decrease of P27^Kip1 (CDKN1B) during naïve CD4⁺ T cell activation, whereas it inhibited the increase of P21^Cip1 (CDKN1A) expression 48 h after mitogenic stimulation. The molecular docking analysis confirmed that these proteins (CD4, CCND1, and CDKN1A) are the primary targets for EGCG, T cell-mediated autoimmune diseases, and MS. Finally, target enrichment analysis indicated that EGCG may affect the cell cycle, T cell receptor signaling pathway, Th cell differentiation, and NF-κB signaling pathway. These findings reveal a crucial role of EGCG in the division and progression of CD4⁺ T cells, and underscore other potential targets of EGCG in T cell-mediated autoimmune diseases such as MS.

Keywords: Cell cycle; EGCG; Molecular docking; Network pharmacology; T cell-mediated autoimmune diseases; multiple sclerosis.