Suppression of Inflammation, Osteoclastogenesis and Bone Loss by PZRAS Extract

Panax ginseng acts on a wide range of mechanisms, such as neuroprotective effect, a skin protective effect and enhanced DNA repair, anti-diabetic activity and against vascular inflammatory. However, the effect of the mixture of extract containing Panax ginseng and its molecular mechanism on bone inflammation has not been clarified. In this study, we sought to discover inhibitory effects of mixture of natural extracts containing Panax ginseng, Ziziphus jujube, Rubi fructus, Artemisiae asiaticae and Scutellaria baicalensis (PZRAS) on osteoclastogenesis and bone remodeling. The PZRAS extract suppressed the level of catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GSH-R) and glutathione peroxidase (GSH-Px) and reduced malondialdehyde (MDA) in lipopolysaccharide (LPS)-treated RAW 264.7 cells. In addition, treatment with PZRAS extract reduced the release of pro-inflammatory cytokines, such as interleukin-1β (IL-1 β) and tumor necrosis factor-α (TNF-α). PZRAS extract was also reduced osteoclast differentiation through inhibiting osteoclast specific genes like matrix metalloproteinase 2 (MMP-2), matrix metalloproteinase 9 (MMP-9), tartrate resistant acid phosphatase (TRAP), and cathepsin K in receptor activator of NF-κB ligand (RANKL)- induced RAW264.7 cells. PZRAS extract also has inhibitory effects on the RANKL-stimulated activation of ERK and JNK which lead to decreased level of NFATc1 and c-Fos. In in vivo study, bone loss induced by LPS were recovered by treatment with PZRAS extract in parameter of bone volume per tissue volume compared to control. Furthermore, the percentage of ES/BS (eroded bone surface near the growth plate) of the femurs significantly increased in the LPS-treated mice compared to vehicle group, but this effect was significantly reversed in PZRAS extract-treated mice. In conclusion, the results mentioned above suggest that PZRAS extract could prevent or treat disorders with abnormal bone loss.

Keywords: PZRAS; anti-inflammatory; antioxidant; bone loss; osteoclastogenesis.