Anti-inflammatory and immunosuppressive effect of phloretin.
This study investigated the effect of phloretin (Ph) on the proliferation, activation, and cell-cycle distribution of mouse T lymphocytes and NO production and phagocytosis of macrophages. Carboxyfluorescein diacetatesuccinimidyl ester (CFDA-SE) staining plus flow cytometry assay was employed to obtain the proliferation-related index (PI) of lymphocytes. The expression levels of CD69 and CD25 on T lymphocytes stimulated with Con A were evaluated with flow cytometry after staining with fluorescent monoclonal antibody. Cell-cycle distribution of T lymphocytes was analyzed by propidium iodide staining. Griess kit was used to evaluate the NO production and fluorescent microbeads were used to analyze the phagocytosis ability of macrophages. Our results showed that phloretin (40, 60, and 80 micromol x L(-7)) significantly inhibited the proliferation of T lymphocytes and the PI reduced from 1.41 +/- 0.13 to 1.34 +/- 0.16, 1.19 +/- 0.12 and 1.07 +/- 0.06, respectively. Phloretin significantly inhibited the expression of CD69 and CD25 (P < 0.01). The cell cycle distribution analysis showed that phloretin could induce a cell cycle arrest at G0/G1 phase. NO production of LPS +IFN-gamma group of macrophages was (26.72 +/- 3.57) micromol x L(-1), and was significantly reduced by phloretin (P < 0.01). And phagocytosis rate of macrophages was significantly reduced by phloretin (P < 0.01). The results demonstrate that phloretin might be developed into a new immuosuppressive drug.
Lu
Xiao-yu
XY
Institute of Tissue Transplantation and Immunology, Jinan University, Guangzhou 510632, China.
Zeng
Yao-ying
YY
Ye
Yan-xia
YX
Zhou
Yu-ying
YY
Mu
Jing-jing
JJ
Zhao
Xiao-hui
XH
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D010693:Phloretin / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D000099192:CD69 Antigens
D000893:Anti-Inflammatory Agents; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit; D037181:Lectins, C-Type; D009569:Nitric Oxide; D010693:Phloretin; D000099192:CD69 Antigens