Green tea EGCG inhibits naïve CD4+ T cell division and progression in mice: An integration of network pharmacology, molecular docking and experimental validation
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. H...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-01-01
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| Series: | Current Research in Food Science |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2665927123001053 |
| _version_ | 1797394795464753152 |
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| author | Xinli Niu Zejin Liu Junpeng Wang Dayong Wu |
| author_facet | Xinli Niu Zejin Liu Junpeng Wang Dayong Wu |
| author_sort | Xinli Niu |
| collection | DOAJ |
| description | 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 P27Kip1 (CDKN1B) during naïve CD4+ T cell activation, whereas it inhibited the increase of P21Cip1 (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. |
| first_indexed | 2024-03-09T00:24:54Z |
| format | Article |
| id | doaj.art-0dc64a83a8524a0ba90f335394eb0430 |
| institution | Directory Open Access Journal |
| issn | 2665-9271 |
| language | English |
| last_indexed | 2024-03-09T00:24:54Z |
| publishDate | 2023-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Current Research in Food Science |
| spelling | doaj.art-0dc64a83a8524a0ba90f335394eb04302023-12-12T04:35:53ZengElsevierCurrent Research in Food Science2665-92712023-01-017100537Green tea EGCG inhibits naïve CD4+ T cell division and progression in mice: An integration of network pharmacology, molecular docking and experimental validationXinli Niu0Zejin Liu1Junpeng Wang2Dayong Wu3Translational Medical Center, Huaihe Hospital of Henan University, Kaifeng, 475000, China; College of Life Science, Henan University, Kaifeng, 475000, China; Nutritional Immunology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, 02111, USATranslational Medical Center, Huaihe Hospital of Henan University, Kaifeng, 475000, ChinaTranslational Medical Center, Huaihe Hospital of Henan University, Kaifeng, 475000, China; Nutritional Immunology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, 02111, USA; Corresponding author. Institute of Infection and Immunity Huaihe Hospital Henan University 115 Ximen Street Kaifeng, 475000, China.Nutritional Immunology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, 02111, USA; Corresponding author. Nutritional Immunology Team Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University Boston, 02111, MA, USA.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 P27Kip1 (CDKN1B) during naïve CD4+ T cell activation, whereas it inhibited the increase of P21Cip1 (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.http://www.sciencedirect.com/science/article/pii/S2665927123001053EGCGNetwork pharmacologyMolecular dockingCell cycleT cell-mediated autoimmune diseasesmultiple sclerosis |
| spellingShingle | Xinli Niu Zejin Liu Junpeng Wang Dayong Wu Green tea EGCG inhibits naïve CD4+ T cell division and progression in mice: An integration of network pharmacology, molecular docking and experimental validation Current Research in Food Science EGCG Network pharmacology Molecular docking Cell cycle T cell-mediated autoimmune diseases multiple sclerosis |
| title | Green tea EGCG inhibits naïve CD4+ T cell division and progression in mice: An integration of network pharmacology, molecular docking and experimental validation |
| title_full | Green tea EGCG inhibits naïve CD4+ T cell division and progression in mice: An integration of network pharmacology, molecular docking and experimental validation |
| title_fullStr | Green tea EGCG inhibits naïve CD4+ T cell division and progression in mice: An integration of network pharmacology, molecular docking and experimental validation |
| title_full_unstemmed | Green tea EGCG inhibits naïve CD4+ T cell division and progression in mice: An integration of network pharmacology, molecular docking and experimental validation |
| title_short | Green tea EGCG inhibits naïve CD4+ T cell division and progression in mice: An integration of network pharmacology, molecular docking and experimental validation |
| title_sort | green tea egcg inhibits naive cd4 t cell division and progression in mice an integration of network pharmacology molecular docking and experimental validation |
| topic | EGCG Network pharmacology Molecular docking Cell cycle T cell-mediated autoimmune diseases multiple sclerosis |
| url | http://www.sciencedirect.com/science/article/pii/S2665927123001053 |
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