title: Inhibitory effect of Carthamus tinctorius L. seed extracts on bone resorption mediated by tyrosine kinase, COX-2 (cyclooxygenase) and PG (prostaglandin) E2.
abstract: Anti-bone resorption properties of the Korean herbal formulation, Honghwain (HHI; Carthamus tinctorius L. seed) was biochemically investigated. On processing bone metabolism, PGE2 accelerated production of IL-1beta in fetal mouse osteoblast and stimulated physiological activation substance, IL-1beta. The novel class of Src tyrosine kinase inhibitors, Herbimycin A (HERB) and HHI reduced COX-2 mRNA levels as well as PGE2 production induced by IL-1beta, TNF-alpha and IL-6. HHI inhibited in vitro and in vivo bone resorption by inhibition of phosphorylation of peptide substrates. HHI dose-dependently reduced the hypercalcemia induced in mice by IL-1beta and partly prevented bone loss and microarchitectural changes in young ovariectomized rats, showing that the protective effect on bone was exerted via the inhibition of bone resorption. These results indicate that the synergy between IL-beta, TNF-alpha, IL-6 on PGE2 production is due to an enhanced gene expression of COX-2 and that tyrosine kinase (s) are involved in the signal transduction of COX-2 in mouse calvarial osteoblasts. Thus, HHI as a possible Src family kinase inhibitor may be useful for the treatment of diseases associated with elevated bone loss.
authors.affiliation: Department of Acupuncture and Moxibustion, College of Oriental Medicine, Woosuk University, Chonbuk, Korea.
authors.forename: Tae Han
authors.initials: TH
authors.lastname: Yuk
authors.forename: Joon Hyeog
authors.initials: JH
authors.lastname: Kang
authors.forename: Sang Ryoung
authors.initials: SR
authors.lastname: Lee
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Yuk
authors.forename: Kwang Gyu
authors.initials: KG
authors.lastname: Lee
authors.forename: Beum Yong
authors.initials: BY
authors.lastname: Song
authors.forename: Cheorl Ho
authors.initials: CH
authors.lastname: Kim
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Kim
authors.forename: Il Kim
authors.initials: IK
authors.lastname: Dong
authors.forename: Tae Kyun
authors.initials: TK
authors.lastname: Lee
authors.forename: Chang Hyun
authors.initials: CH
authors.lastname: Lee
mesh_terms: D000818:Animals; D016227:Benzoquinones; D001862:Bone Resorption / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D001842:Bone and Bones / Q000473:pathology; D031178:Carthamus / Q000737:chemistry*; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D016207:Cytokines / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology*; D005260:Female; D006934:Hypercalcemia / Q000097:blood / Q000188:drug therapy; D007527:Isoenzymes / Q000096:biosynthesis / Q000378:metabolism*; D047029:Lactams, Macrocyclic; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects; D010024:Osteoporosis / Q000139:chemically induced / Q000517:prevention & control; D010052:Ovariectomy; D010281:Parathyroid Hormone / Q000037:antagonists & inhibitors / Q000633:toxicity; D010936:Plant Extracts / Q000494:pharmacology*; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011809:Quinones / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D017828:Rifabutin / Q000031:analogs & derivatives; D012639:Seeds / Q000737:chemistry
chemical_list: D016227:Benzoquinones; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D007527:Isoenzymes; D047029:Lactams, Macrocyclic; D008565:Membrane Proteins; D010281:Parathyroid Hormone; D010936:Plant Extracts; D011448:Prostaglandin Antagonists; D011809:Quinones; D012333:RNA, Messenger; D017828:Rifabutin; C020754:herbimycin; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D011505:Protein-Tyrosine Kinases; D015232:Dinoprostone