Inhibition of prostaglandin and nitric oxide production in lipopolysaccharide-treated RAW 264.7 cells by tanshinones from the roots of Salvia miltiorrhiza bunge.
This study examined the effects of tanshinone derivatives (tanshinone I, cryptotanshinone, 15,16-dihydrotanshinone I) on prostaglandin (PG) and nitric oxide (NO) metabolism in an attempt to establish their anti-inflammatory mechanisms and to present a scientific rationale for the use of Salvia miltiorrhiza (danshen) in inflammatory conditions. From lipopolysaccharide-treated RAW 264.7 cells, cyclooxygenase-2 (COX-2)-mediated PGE2 production was inhibited by tanshinone I, cryptotanshinone and 15,16-dihydrotanshinone I, while only cryptotanshinone and 15,16-dihydrotanshinone I inhibited inducible NO synthase (iNOS)-mediated NO synthesis at 1-50 microM. Particularly, cryptotanshinone was found to be a down-regulator of proinflammatory molecule expression, including COX-2 and iNOS. The electrophoretic mobility shift assay showed that cryptotanshinone and 15,16-dihydrotanshinone I also inhibited the activation of the transcription factors, such as nuclear transcription factor-kappaB and activator protein-1. Moreover, cryptotanshinone exhibited in vivo anti-inflammatory activity against carrageenan-induced paw edema in rats. Overall, these results provide additional scientific rationale for the anti-inflammatory use of danshen in Chinese medicine. Especially, cryptotanshinone and 15,16-dihydrotanshinone I are important constituents.
Jeon
Su Jin
SJ
Dept. Food and Nutrition, Andong National University, Andong, 760-749, Korea.
Son
Kun Ho
KH
Kim
Yeong Shik
YS
Choi
Yong Hwan
YH
Kim
Hyun Pyo
HP
D045784:Abietanes; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000302:isolation & purification / Q000494:pharmacology*; D002351:Carrageenan; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004487:Edema / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D024202:Electrophoretic Mobility Shift Assay; D005663:Furans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D010616:Phenanthrenes / Q000302:isolation & purification / Q000494:pharmacology*; D018517:Plant Roots; D011809:Quinones; D051381:Rats; D017207:Rats, Sprague-Dawley; D027561:Salvia miltiorrhiza / Q000737:chemistry
D045784:Abietanes; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D005663:Furans; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010616:Phenanthrenes; D011809:Quinones; C021751:tanshinone; D009569:Nitric Oxide; C000713095:dihydrotanshinone I; C037886:cryptotanshinone; D002351:Carrageenan; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D015232:Dinoprostone