Inhibition of lymphocyte proliferation by the anti-arthritic drug sinomenine

The effect on lymphocyte proliferation of sinomenine, a pure alkaloid extracted from the Chinese medical plant Sinomenium acutum was investigated in vitro using mouse spleen cells and human peripheral blood mononuclear cells. It could be demonstrated that sinomenine markedly inhibited [3H]thymidine incorporation in mouse spleen cells activated with concanavalin A (IC50 = 400 microM) or by two-way mixed lymphocyte culture (IC50 = 60 microM) and also in human peripheral blood mononuclear cells activated with phytohemagglutinin, 12-O-tetradecanoylphorbol-13-acetate plus ionomycin, or mixed lymphocyte culture (IC50 ranging from 34 to 129 microM). Time kinetic experiments revealed that sinomenine was effective only when added within the first 48 h after the onset of mixed lymphocyte culture, which lasted for 5 days. Inhibition of lymphocyte proliferation by sinomenine was reversible. Accordingly, the drug showed no direct cytotoxicity in our cellular systems and had no inhibitory effect on the proliferation of the cytokine-independent growth of the human leukaemic T-cell lymphoblast cell line Jurkat. It can be considered that these anti-proliferative effects are part of the anti-inflammatory and anti-arthritic mechanisms of sinomenine obvious in clinical trials.