Inhibitory Effects of Berberine on the Activation and Cell Cycle Progression of Human Peripheral Lym

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The immunosuppressive property of berberine,an isoquinoline alkaloid,has been well documented,but themechanism of its action on lymphocytes has not been completely elucidated.The present study is to investigate theeffect of berberine on the activation and proliferation of lymphocytes,in particular T lymphocytes.Wholeperipheral blood from healthy donors was stimulated with phytohemagglutinin (PHA) alone or phorbol dibutyrate(PDB) plus ionomycin,and the expression of CD69 and CD25 on T lymphocytes was evaluated with flow cytometry.The distribution of cell cycles and cell viability were analyzed by staining with propidium iodide (PI) and7-aminoactinomycin D (7-AAD),respectively.The results showed that 100 μmol/L and 50 μmol/L of berberinesignificantly inhibited CD69 expression on T cells stimulated with PDB plus ionomycin or PHA,whereas the effectof 25 μmol/L berberine was not significant.As the incubation time increased,the extent of inhibition decreased.Similarly,the expression of CD25 was also reduced by berberine in a dose-dependent manner over theconcentration range of 25-100 μmol/L.Besides,this alkaloid could block lymphocyte cell cycle progression fromG_0/G_1 phase to S and G_2/M phase without phase specificity.Moreover,analysis following 7-AAD staining revealedthat berberine had no significant cytotoxicity on lymphocytes.Taken together,berberine significantly inhibits theexpression of activation antigens on T lymphocytes and also blocks the progression of cell cycles of lymphocytes,suggesting that berberine may exert immunosuppressive effect through inhibiting the activation and proliferationofT cells.Cellular & Molecular Immunology.2005;2(4):295-300. The immunosuppressive property of berberine, an isoquinoline alkaloid, has been well documented, but themechanism of its action on lymphocytes has not been completely elucidated. The present study is to investigate the effect of berberine on the activation and proliferation of lymphocytes, in particular T lymphocytes. Wholeperipheral blood from healthy donors was stimulated with phytohemagglutinin (PHA) alone or phorbol dibutyrate(PDB) plus ionomycin, and the expression of CD69 and CD25 on T lymphocytes was evaluated with flow cytometry. The distribution of cell cycles and cell viability were studied by staining. With propidium iodide (PI) and7-aminoactinomycin D (7-AAD),respectively.The results showed that 100 μmol/L and 50 μmol/L of berberinesignificantly inhibited CD69 expression on T cells stimulated with PDB plus ionomycin or PHA,whereas the effectof 25 μmol/L berberine was not significant.As the incubation time increased, the extent of damping declined.Similarly, the expression of CD 25 was reduced by berberine in a dose-dependent manner over the concentration range 25-100 μmol/L.Besides, this alkaloid could block lymphocyte cell cycle progression from G_0/G_1 phase to S and G_2/M phase without phase specificity.Moreover, Analysis following 7-AAD staining revealedthat berberine had no significant cytotoxicity on lymphocytes.Taken together,berberine significantly inhibits the expression of activation antigens on T lymphocytes and also blocks the progression of cell cycles of lymphocytes,suggesting that berberine may exert immunosuppressive effect through inhibiting the activation And proliferation of T cells. Cellular & Molecular Immunology. 2005;2(4):295-300.
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