Salvia plebeia R.Br. inhibits signal transduction of IL-6 and prevents ovariectomy-induced bone loss by suppressing osteoclastogenesis

• Published in: Archives of pharmacal research 2016, 39(12), , pp.1671-1681
• Main Authors: Kim, Mi-Hwa, Jung, Kyungsook, Nam, Ki-Hoan, Jang, Hyun-Jae, Lee, Seung Woong, Kim, Yesol, Park, Chan Sun, Lee, Tae-Hoon, Park, Jee Hun, Choi, Jung Ho, Rho, Mun-Chual, Oh, Hyun-Mee
• Format: Article
• Language: English
• Subjects: Animals; Bone Resorption - etiology; Bone Resorption - metabolism; Bone Resorption - prevention & control; Cells, Cultured; Dose-Response Relationship, Drug; Female; Humans; Interleukin-6 - antagonists & inhibitors; Interleukin-6 - metabolism; Medicine; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Osteogenesis - drug effects; Osteogenesis - physiology; Ovariectomy - adverse effects; Pharmacology/Toxicology; Pharmacy; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Research Article; Salvia; Signal Transduction - drug effects; Signal Transduction - physiology; 약학
• ISSN: 0253-6269; 1976-3786
• DOI: 10.1007/s12272-016-0810-0

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.