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

Phytotherapy Research
2002.0

Abstract

<jats:title>Abstract</jats:title><jats:p>Arachidonic acid (AA) mainly released from the cell membrane by phospholipase A<jats:sub>2</jats:sub> (PLA<jats:sub>2</jats:sub>) 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<jats:sub>2</jats:sub> and COX‐2, 300 plant extracts were evaluated for their inhibitory activity on PGD<jats:sub>2</jats:sub> production from cytokine‐induced mouse bone marrow‐derived mast cells <jats:italic>in vitro</jats:italic>. From this screening procedure, the methanol extract of <jats:italic>Salvia miltiorrhiza</jats:italic> was found to inhibit PGD<jats:sub>2</jats:sub> 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 <jats:italic>in vivo</jats:italic> antiinflammatory activity. Tanshinone I inhibited PGE<jats:sub>2</jats:sub> formation from LPS‐induced RAW macrophages (IC<jats:sub>50</jats:sub> = 38 μ<jats:sc>M</jats:sc>). 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<jats:sub>2</jats:sub>(IC<jats:sub>50</jats:sub> = 11 μ<jats:sc>M</jats:sc>) and rabbit recombinant cPLA<jats:sub>2</jats:sub> (IC<jats:sub>50</jats:sub> = 82 μ<jats:sc>M</jats:sc>). In addition, tanshinone I showed <jats:italic>in vivo</jats:italic> antiinflammatory activity in rat carrageenan‐induced paw oedema and adjuvant‐induced arthritis. Copyright © 2002 John Wiley &amp; Sons, Ltd.

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