Effects of tanshinone I isolated from Salvia miltiorrhiza Bunge on arachidonic acid metabolism and in vivo inflammatory responses

Arachidonic acid (AA) mainly released from the cell membrane by phospholipase A 2 (PLA 2 ) is converted to eicosanoids by the action of cyclooxygenase (COX) and lipoxygenase (LO). In order to find the specific inhibitors of AA metabolism especially PLA 2 and COX‐2, 300 plant extracts were evaluated for their inhibitory activity on PGD 2 production from cytokine‐induced mouse bone marrow‐derived mast cells in vitro . From this screening procedure, the methanol extract of Salvia miltiorrhiza was found to inhibit PGD 2 production and the ethyl acetate subfraction gave the strongest inhibition of five subfractions tested. From this ethyl acetate subfraction, an activity‐guided isolation finally gave tanshinone I as an active principle. This investigation deals with the effects of tanshinone I on AA metabolism from lipopolysaccharide (LPS)‐induced RAW 264.7 cells and in vivo antiinflammatory activity. Tanshinone I inhibited PGE 2 formation from LPS‐induced RAW macrophages (IC 50  = 38 μ M ). However, this compound did not affect COX‐2 activity or COX‐2 expression. Tanshinone I was found to be an inhibitor of type IIA human recombinant sPLA 2 (IC 50  = 11 μ M ) and rabbit recombinant cPLA 2 (IC 50  = 82 μ M ). In addition, tanshinone I showed in vivo antiinflammatory activity in rat carrageenan‐induced paw oedema and adjuvant‐induced arthritis. Copyright © 2002 John Wiley & Sons, Ltd.