acid-phosphatase and scoparone

Scoparone, one of the bioactive components of Artemisia capillaris Thunb, has various biological properties including immunosuppressive, hepatoprotective, anti-allergic, anti-inflammatory, and antioxidant effects. This study aims at evaluating the anti-osteoporotic effect of scoparone and its underlying mechanism in vitro. Scoparone demonstrated potent cellular antioxidant capacity. It was also found that scoparone inhibited the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and suppressed cathepsin K and tartrate-resistant acid phosphatase (TRAP) expression via c-jun N-terminal kinase (JNK)/extracellular signal-regulated kinase (ERK)/p38-mediated c-Fos-nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) signaling pathway. During osteoclast differentiation, the production of general reactive oxygen species (ROS) and superoxide anions was dose-dependently attenuated by scoparone. In addition, scoparone diminished NADPH (nicotinamide adenine dinucleotide phosphate) oxidase 1 (Nox1) expression and activation via the tumor necrosis factor receptor-associated factor 6 (TRAF6)-cSrc-phosphatidylinositol 3-kinase (PI3k) signaling pathway and prevented the disruption of mitochondrial electron transport chain system. Furthermore, scoparone augmented the expression of superoxide dismutase 1 (SOD1) and catalase (CAT). The overall results indicate that the inhibitory effect of scoparone on RANKL-induced osteoclast differentiation is attributed to the suppressive effect on ROS and superoxide anion production by inhibiting Nox1 expression and activation and protecting the mitochondrial electron transport chain system and the scavenging effect of ROS resulting from elevated SOD1 and CAT expression.

Topics: Acid Phosphatase; Animals; Bone Remodeling; Catalase; Cathepsin K; Cell Differentiation; Cell Line, Tumor; Coumarins; Extracellular Signal-Regulated MAP Kinases; Free Radical Scavengers; Isoenzymes; JNK Mitogen-Activated Protein Kinases; Mice; NADH, NADPH Oxidoreductases; NADPH Oxidase 1; NFATC Transcription Factors; Osteoclasts; Oxidative Phosphorylation; p38 Mitogen-Activated Protein Kinases; Phosphatidylinositol 3-Kinase; Proto-Oncogene Proteins c-fos; RANK Ligand; Reactive Oxygen Species; Signal Transduction; Superoxide Dismutase; Superoxide Dismutase-1; Superoxides; Tartrate-Resistant Acid Phosphatase; TNF Receptor-Associated Factor 6; Up-Regulation