Antiproliferative effects of magnosalin derived from ‘Shin'i’ (Flos Magnoliae), a Japanese Sino-medicine,on cultured synovial cells of MRL/1 and C57BL/6J mice

The in vitro inhibitory effect of magnosalin, a compound derived from ‘Shin'i’ (Flos Magnoliae), on the proliferation of synovial cells from rheumatoid MRL/1 mice and normal C57BL/6J mice (control) was evaluated. DNA synthesis in synovial cells was induced with 5% fetal bovine serum (FBS) or interleukin-1α (IL-1α, 1 U/mL), and measured with a ³H]-thymidine incorporation assay. Basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) were used in some experiments. FBS (5%)-stimulated proliferation (cell number) was significantly greater in MRL/1 mouse synovial cells than in C57BL/6J synovial cells. Magnosalin (23.9 μM ) inhibited ³H]-thymidine incorporation into both MRL/1 and C57BL/6J mouse synovial cells, whereas magnoshinin (23.4 μM ) inhibited ³H]-thymidine incorporation only into normal C57BL/6J synovial cells. Corticosterone, bucillamine, and tetrandrine, positive controls, also inhibited ³H]-thymidine incorporation into synovial cells. Reticuline (100 μM ) and coclaurine (100 μM ), structural moieties of tetrandrine, had no significant effects except for an inhibitory effect of coclaurine on normal C57BL/6J cells. Butylidenephthalide (100 μM ), a compound derived from Cnidium Rhizome, did not inhibit ³H]-thymidine incorporation into synovial cells of MRL/1 or normal mice. IL-1α, bFGF, and PDGF each stimulated ³H]-thymidine incorporation into synovial cells of normal mice in a concentration-dependent manner in the presence of 1% FBS. Of these cytokines, IL-1α was the most effective at the lowest concentration (0.57 pM ; 1 U/mL); it was as effective as 5% FBS. Both magnosalin (2.39 μM ) and tetrandrine (0.1 μM ) inhibited IL-1α (1 U/mL)-induced ³H]-thymidine incorporation into normal C57BL/6J synovial cells. Magnosalin appears to be an important lead compound for the development of a new class of antirheumatic agents.