title: Regulation of osteoclastogenesis by Simon extracts composed of caffeic acid and related compounds: successful suppression of bone destruction accompanied with adjuvant-induced arthritis in rats.
abstract: Simon extracts are vitamin K(1)-rich food materials extracted from the leaves of the Simon sweet potato. Although vitamin K is known to stimulate bone formation, we postulated that Simon extracts also contain unknown biological compounds having the ability to regulate bone resorption. Here we prepared the vitamin K-free fraction from the Simon extracts and investigated the ability of this fraction on the differentiation of osteoclasts. A remarkable inhibitory effect of osteoclastogenesis was observed when osteoclast precursors were treated with this fraction in rat bone marrow culture systems as well as in a pure differentiation system using murine osteoclast precursor cell line. The vitamin K-free Simon extracts markedly suppressed severe bone destruction mediated by abundant osteoclasts associated with adjuvant-induced arthritis in rats. High performance liquid chromatography (HPLC) analysis revealed that the vitamin K-free Simon extracts contained three types of low molecular weight inhibitors for osteoclastogenesis; caffeic acid, chlorogenic acids and isochlorogenic acids. Among these substances, caffeic acid showed the most powerful inhibitory effects on osteoclastogenesis. Caffeic acid significantly suppressed expression of NFATc1, a key transcription factor for the induction of osteoclastogenesis. Our current study enlightened a high utility of the Simon extracts and their chemical components as effective regulators for bone resorption accompanied with inflammation and metabolic bone diseases.
authors.affiliation: Oral Cellular and Molecular Biology, Kyushu University, Maidashi 3-1-1, Fukuoka, 812-8582, Japan.
authors.forename: Quan Yong
authors.initials: QY
authors.lastname: Tang
authors.forename: Toshio
authors.initials: T
authors.lastname: Kukita
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ushijima
authors.forename: Akiko
authors.initials: A
authors.lastname: Kukita
authors.forename: Kengo
authors.initials: K
authors.lastname: Nagata
authors.forename: Ferry
authors.initials: F
authors.lastname: Sandra
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Watanabe
authors.forename: Kazuko
authors.initials: K
authors.lastname: Toh
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Okuma
authors.forename: Sadamichi
authors.initials: S
authors.lastname: Kawasaki
authors.forename: Linda
authors.initials: L
authors.lastname: Rasubala
authors.forename: Junpei
authors.initials: J
authors.lastname: Teramachi
authors.forename: Ichiko
authors.initials: I
authors.lastname: Miyamoto
authors.forename: Zhou
authors.initials: Z
authors.lastname: Wu
authors.forename: Tadahiko
authors.initials: T
authors.lastname: Iijima
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D001483:Base Sequence; D001862:Bone Resorption / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D002109:Caffeic Acids / Q000494:pharmacology*; D056657:Cathepsin K; D002403:Cathepsins / Q000235:genetics; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D066298:In Vitro Techniques; D027723:Ipomoea batatas / Q000737:chemistry; D008297:Male; D010010:Osteoclasts / Q000187:drug effects* / Q000473:pathology; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014812:Vitamin K / Q000302:isolation & purification
chemical_list: D002109:Caffeic Acids; D017931:DNA Primers; D010936:Plant Extracts; D053246:Receptor Activator of Nuclear Factor-kappa B; D014812:Vitamin K; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D002403:Cathepsins; D056657:Cathepsin K; C534133:Ctsk protein, rat; C040048:caffeic acid