INHIBITION OF IN-VITRO LYMPHOCYTE-TRANSFORMATION BY THE ISOQUINOLINE ALKALOID BERBERINE

Berberine is an isoquinoline alkaloid with multiple pharmacological ac tions, including an anti-inflammatory activity. The effects of berberi ne on in-vitro cellular proliferation of human peripheral lymphocytes stimulated with phytohaemagglutinin, concanavalin A and pokeweed mitog en were studied. Mononuclear cells were cultured in flat-bottomed 96-w ell microplates at 37 degrees C for 96-144h in the presence of one mit ogen at different concentrations and the alkaloid at doses of 2.5 to 2 0 mu gmL(-1). The mitogen-induced response of lymphocytes was evaluate d from the extent of the incorporation of [H-3]thymidine into cells in vitro. A consistent and progressive inhibitory influence of berberine with increasing concentrations in culture was identified with all mit ogens and was more pronounced with pokeweed mitogen. The effect of ber berine was observed in phytohaemagglutinin (PHA)- and concanavalin A-a ctivated lymphocytes when the drug was added during the first 24h of c ulture, whereas the same effect occurred throughout the incubation per iod in pokeweed mitogen-stimulated cells. The viability of lymphocytes following treatment with the drug, as assessed by the trypan blue exc lusion test, revealed no change when compared with the same untreated lymphocytes, indicating no lymphocytotoxic activity. We conclude that some effects of berberine, especially its anti-inflammatory action, ma y arise in part from the inhibition of DNA-synthesis in activated lymp hocytes.