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 microM). 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 microM) and rabbit recombinant cPLA(2) (IC(50) = 82 microM). In addition, tanshinone I showed in vivo antiinflammatory activity in rat carrageenan-induced paw oedema and adjuvant-induced arthritis.
Kim
Sung Young
SY
College of Pharmacy, Kangwon National University, Chunchon 200-701, Korea.
Moon
Tae Cheol
TC
Chang
Hyeun Wook
HW
Son
Kun Ho
KH
Kang
Sam Sik
SS
Kim
Hyun Pyo
HP
D045784:Abietanes; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D016718:Arachidonic Acid / Q000493:pharmacokinetics*; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D015153:Blotting, Western; D002351:Carrageenan; D051546:Cyclooxygenase 2; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D006801:Humans; D020128:Inhibitory Concentration 50; D007527:Isoenzymes / Q000096:biosynthesis / Q000187:drug effects; D008297:Male; D008407:Mast Cells / Q000187:drug effects; D008565:Membrane Proteins; D051379:Mice; D010616:Phenanthrenes / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D015230:Prostaglandin D2 / Q000096:biosynthesis / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D027561:Salvia miltiorrhiza
D045784:Abietanes; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007527:Isoenzymes; D008565:Membrane Proteins; D010616:Phenanthrenes; D010936:Plant Extracts; C021751:tanshinone; D016718:Arachidonic Acid; D002351:Carrageenan; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015230:Prostaglandin D2