Anti-osteoclastogenic effect and action mechanism of the sargachromanol G isolated from Sargassum siliquastrum

Abstract

Inflammatory bone diseases are characterized by the presence of pro-inflammatory cytokines that regulate bone turnover. The receptor activator of NF-κB ligand (RANKL) is a soluble osteoblast-derived protein that induces bone resorption through osteoclast differentiation and activation. Sargachromanol G is isolated from Sargassum siliquastrum and has cytotoxicity, antioxidant, and antiviral activities. The active components and underlying mechanisms of its anti-osteoclastogenic activity remain largely unknown. In the present study, we investigated the anti-osteoclastogenic effects of sargachromanol G isolated from S. siliquastrum on the expression of IL-1β-induced osteoclastogenic factors (RANKL, IL-6, PGE2 and COX-2) in human osteoblast MG-63 cells, as well as LPS or RANKL-induced pro-inflammatory factors and osteoclastogenic factors (nitric oxide (NO), cytokines (TNF-α, IL-1β and IL-6), TRAP, CTR, TRAF6, Cath-K, and MMP-9) in murine macrophage RAW 264.7 cells. We also examined the role of nuclear factor-κB (NF-κB) and mitogen activated protein kinase (MAPK) signaling induced by IL-1β in MG-63 and LPS or RANKL in RAW 264.7 cells. Sargachromanol G dose-dependently inhibited the production of osteoclastogenic factors in MG-63 and RAW 264.7 cells. Sargachromanol G also inhibited phosphorylation of NF-κB (IκB-α, p65 and p50) and MAPK (ERK1/2, JNK and p38). These results suggest that the anti-osteoclastogenic activity of sargachromanol G isolated from S. siliquastrum may result from modulation of osteoclastogenic factors and cytokines via suppression of phospholrylated MAPK and NF-κB activation.