The anti-inflammatory activities of Tanshinone IIA, an active component of TCM, are mediated by estrogen receptor activation and inhibition of iNOS.
Tanshinone IIA (Tan IIA) is a major compound extracted from a traditional herbal medicine Salvia miltiorrhiza BUNGE, which is used to treat cardiovascular diseases, cerebrovascular diseases and postmenopausal syndrome. It has also been shown to possess anti-inflammatory activity. Since Tan IIA has a similar structure to that of 17beta-estradiol (E(2)), the present study was undertaken to characterize the estrogenic activity of Tan IIA and to demonstrate a functional role of this activity in RAW 264.7 cells. In transient transfection assay, Tan IIA (10 microM) increases ERE-luciferase activity in an estrogen receptor (ER) subtype-dependent manner when either ERalpha or ERbeta were co-expressed in Hela cells. In LPS-induced RAW 264.7 cells, Tan IIA exerts anti-inflammatory effects by inhibition of iNOS gene expression and NO production, as well as inhibition of inflammatory cytokine (IL-1beta, IL-6, and TNF-alpha) expression via ER-dependent pathway. Therefore, it could serve as a potential selective estrogen receptor modulator (SERM) to treat inflammation-associated neurodegenerative and cardiovascular diseases without increasing the risk of breast cancer.
Fan
Guan-Wei
GW
Institute of Traditional Chinese Medicine Research, Tianjin University of Traditional Chinese Medicine, 312 Anshanxi Road, Tianjin, China.
Gao
Xiu-Mei
XM
Wang
Hong
H
Zhu
Yan
Y
Zhang
Ju
J
Hu
Li-Min
LM
Su
Yan-Fang
YF
Kang
Li-Yuan
LY
Zhang
Bo-Li
BL
D045784:Abietanes; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004365:Drugs, Chinese Herbal; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects*; D008516:Medicine, Chinese Traditional; D051379:Mice; D015394:Molecular Structure; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D010616:Phenanthrenes / Q000737:chemistry / Q000494:pharmacology*; D027561:Salvia miltiorrhiza / Q000737:chemistry*
D045784:Abietanes; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D008070:Lipopolysaccharides; D010616:Phenanthrenes; C021751:tanshinone; D009569:Nitric Oxide; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II