title: Salvia plebeia R.Br. inhibits signal transduction of IL-6 and prevents ovariectomy-induced bone loss by suppressing osteoclastogenesis.
abstract: The interleukin-6 (IL-6) family of cytokines plays a key role in the pathogenesis of rheumatoid arthritis and osteoporosis through the regulation of bone formation and resorption. In this study, it was observed that ethanol extract of Salvia plebeia R.Br. (S.P-EE) inhibited IL-6-induced signaling cascade including phosphorylation of JAK2/STAT3 and ERK. Subsequently, it was examined whether S.P-EE treatment could recover bone loss in ovariectomized (OVX) mice. Indeed, S.P-EE exhibited both preventive and therapeutic effect on OVX-induced bone loss in trabecular microarchitecture along with significant increase in bone mineral density and content. To understand the mechanism of action of S.P-EE in bone metabolism, the effect of S.P-EE on osteoclast differentiation and activity was investigated. S.P-EE significantly inhibited RANKL-induced osteoclast differentiation by suppressing phosphorylation of MAPK and Akt, and expression of NFATc1 and osteoclast marker genes. S.P-EE also inhibited bone-resorbing activity of osteoclasts. Furthermore, isolation and identification of the active compounds which are responsible for the inhibitory effect of S.P-EE on osteoclast differentiation was carried out. Six major flavonoids and plebeiolide A-C were isolated and examined their effects on osteoclast differentiation. Luteolin and hispidulin, and plebeiolide A and C, not B exhibited potent inhibitory activity on RANKL-induced osteoclast formation.
authors.affiliation: Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 1404 Sinjeong-dong, Jeongeup-si, Jeonbuk, 580-185, Republic of Korea.|Interdisciplinary Graduate Program in Molecular Medicine, Chonnam National University, Gwangju, 501-746, Republic of Korea.
authors.forename: Mi-Hwa
authors.initials: MH
authors.lastname: Kim
authors.affiliation: Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 1404 Sinjeong-dong, Jeongeup-si, Jeonbuk, 580-185, Republic of Korea.
authors.forename: Kyungsook
authors.initials: K
authors.lastname: Jung
authors.affiliation: Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Ochang-eup, Cheongwon-gun, Chungbuk, 36-883, Republic of Korea.
authors.forename: Ki-Hoan
authors.initials: KH
authors.lastname: Nam
authors.affiliation: Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 1404 Sinjeong-dong, Jeongeup-si, Jeonbuk, 580-185, Republic of Korea.
authors.forename: Hyun-Jae
authors.initials: HJ
authors.lastname: Jang
authors.affiliation: Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 1404 Sinjeong-dong, Jeongeup-si, Jeonbuk, 580-185, Republic of Korea.
authors.forename: Seung Woong
authors.initials: SW
authors.lastname: Lee
authors.affiliation: Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 1404 Sinjeong-dong, Jeongeup-si, Jeonbuk, 580-185, Republic of Korea.
authors.forename: Yesol
authors.initials: Y
authors.lastname: Kim
authors.affiliation: Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 1404 Sinjeong-dong, Jeongeup-si, Jeonbuk, 580-185, Republic of Korea.
authors.forename: Chan Sun
authors.initials: CS
authors.lastname: Park
authors.affiliation: Interdisciplinary Graduate Program in Molecular Medicine, Chonnam National University, Gwangju, 501-746, Republic of Korea.|Department of Oral Biochemistry, Dental Science Research Institute, Medical Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, 500-757, Republic of Korea.
authors.forename: Tae-Hoon
authors.initials: TH
authors.lastname: Lee
authors.affiliation: R&D Center, Korean Drug Co., Ltd., Seoul, 135-270, Republic of Korea.
authors.forename: Jee Hun
authors.initials: JH
authors.lastname: Park
authors.affiliation: R&D Center, Korean Drug Co., Ltd., Seoul, 135-270, Republic of Korea.
authors.forename: Jung Ho
authors.initials: JH
authors.lastname: Choi
authors.affiliation: Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 1404 Sinjeong-dong, Jeongeup-si, Jeonbuk, 580-185, Republic of Korea. rho-m@kribb.re.kr.
authors.forename: Mun-Chual
authors.initials: MC
authors.lastname: Rho
authors.affiliation: Natural Product Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 1404 Sinjeong-dong, Jeongeup-si, Jeonbuk, 580-185, Republic of Korea. ohhm@kribb.re.kr.
authors.forename: Hyun-Mee
authors.initials: HM
authors.lastname: Oh
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D010052:Ovariectomy / Q000009:adverse effects*; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D027544:Salvia; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D000093242:Interleukin-6 Inhibitors
chemical_list: D015850:Interleukin-6; D010936:Plant Extracts; D000093242:Interleukin-6 Inhibitors
keywords: Bone mineral density; Interleukin-6; Osteoclast; Osteoporosis; Salvia plebeia R.Br.