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 A2 (PLA2) is converted to eicosanoids by the action of cyclooxygenase (COX) and lipoxygenase (LO). In order to find the specific inhibitors of AA metabolism especially PLA2 and COX‐2, 300 plant extracts were evaluated for their inhibitory activity on PGD2 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 PGD2 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 PGE2 formation from LPS‐induced RAW macrophages (IC50 = 38 μM). 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 sPLA2(IC50 = 11 μM) and rabbit recombinant cPLA2 (IC50 = 82 μM). 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.