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 Vol. 39; no. 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: Journal Article
• Language: English
• Published: Seoul Pharmaceutical Society of Korea 01.12.2016; 대한약학회
• Subjects: active ingredients; Animals; bone density; bone formation; bone resorption; Bone Resorption - etiology; Bone Resorption - metabolism; Bone Resorption - prevention & control; Cells, Cultured; Dose-Response Relationship, Drug; ethanol; Female; genetic markers; Humans; interleukin-6; Interleukin-6 - antagonists & inhibitors; Interleukin-6 - metabolism; luteolin; mechanism of action; Medicine; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; mitogen-activated protein kinase; osteoclasts; Osteogenesis - drug effects; Osteogenesis - physiology; osteoporosis; ovariectomy; Ovariectomy - adverse effects; pathogenesis; Pharmacology/Toxicology; Pharmacy; phosphorylation; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Plant Extracts - therapeutic use; Research Article; resorption; rheumatoid arthritis; Salvia; Salvia plebeia; signal transduction; Signal Transduction - drug effects; Signal Transduction - physiology; 약학; Osteoporosis; R.Br; Bone mineral density; Osteoclast; Interleukin-6; Salvia plebeia R.Br
• ISSN: 0253-6269; 1976-3786; 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.