ANTIPROLIFERATIVE EFFECTS OF MAGNOSALIN DERIVED FROM SHINI (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 evaluate d. DNA synthesis in synovial cells was induced with 5% fetal bovine se rum (FBS) or interleukin-1 alpha (IL-1 alpha, 1 U/mL), and measured wi th a [H-3]-thymidine incorporation assay. Basic fibroblast growth fact or (bFGF) and platelet-derived growth factor (PDGF) were used in some experiments. FBS (5%)-stimulated proliferation (cell number) was signi ficantly greater in MRL/1 mouse synovial cells than in C57BL/6J synovi al cells. Magnosalin (23.9 mu M) inhibited [H-3]-thymidine incorporati on into both MRL/1 and C57BL/6J mouse synovial cells, whereas magnoshi nin (23.4 mu M) inhibited [H-3]-thymidine incorporation only into norm al C57BL/6J synovial cells. Corticosterone, bucillamine, and tetrandri ne, positive controls, also inhibited [H-3]-thymidine incorporation in to synovial cells. Reticuline (100 mu M) and coclaurine (100 mu M), st ructural moieties of tetrandrine, had no significant effects except fo r an inhibitory effect of coclaurine on normal C57BL/6J cells. Butylid enephthalide (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]-thym idine incorporation into synovial cells of normal mice in a concentrat ion-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]-th ymidine 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.