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-1 alpha (IL-1 alpha, 1 U/mL), and measured with a [H-3]-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 mu M) inhibited [H-3]-thymidine incorporation into both MRL/1 and C57BL/6J mouse synovial cells, whereas magnoshinin (23.4 mu M) inhibited [H-3]-thymidine incorporation only into normal C57BL/6J synovial cells. Corticosterone, bucillamine, and tetrandrine, positive controls, also inhibited [H-3]-thymidine incorporation into synovial cells. Reticuline (100 mu M) and coclaurine (100 mu M), structural moieties of tetrandrine, had no significant effects except for an inhibitory effect of coclaurine on normal C57BL/6J cells. Butylidenephthalide (100 mu M), a compound derived from Cnidium Rhizome, did not inhibit [H-3]-thymidine incorporation into synovial cells of MRL/1 or normal mice. IL-1 alpha, bFGF, and PDGF each stimulated [H-3]-thymidine incorporation into synovial cells of normal mice in a concentration-dependent manner in the presence of 1% FBS. Of these cytokines, IL-1 alpha was the most effective at the lowest concentration (0.57 pM; 1U/mL); it was as effective as 5% FBS. Both magnosalin (2.39 mu M) and tetrandrine (0.1 mu M) inhibited IL-1 alpha (1 U/mL)-induced [H-3]-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.