Suppression of Inflammation, Osteoclastogenesis and Bone Loss by PZRAS Extract

J Microbiol Biotechnol. 2020 Oct 28;30(10):1543-1551. doi: 10.4014/jmb.2004.04016.

Abstract

Panax ginseng has a wide range of activities including a neuroprotective effect, skin protective effects, enhanced DNA repairing, anti-diabetic activity, and protective effects against vascular inflammation. In the present study, we sought to discover the inhibitory effects of a mixture of natural products containing Panax ginseng, Ziziphus jujube, Rubi fructus, Artemisiae asiaticae and Scutellaria baicalensis (PZRAS) on osteoclastogenesis and bone remodeling, as neither the effects of a mixture containing Panax ginseng extract, nor its molecular mechanism on bone inflammation, have been clarified yet. PZRAS upregulated the levels of catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GSH-R) and glutathione peroxidase (GSH-Px) and reduced malondialdehyde (MDA) in LPS-treated RAW264.7 cells. Moreover, treatment with PZRAS decreased the production of IL-1β and TNF-α. PZRAS also inhibited osteoclast differentiation through inhibiting osteoclastspecific genes like MMP-2, 9, cathepsin K, and TRAP in RANKL-treated RAW264.7 cells. Additionally, PZRAS has inhibitory functions on the RANKL-stimulated activation of ERK and JNK, which lead to a decrease in the expression of NFATc1 and c-Fos. In an in vivo study, bone resorption induced by LPS was recovered by treatment with PZRAS in bone volume per tissue volume (BV/TV) compared to control. Furthermore, the ratio of eroded bone surface of femurs was significantly increased in LPStreated mice compared to vehicle group, but this ratio was significantly reversed in PZRAS-treated mice. These results suggest that PZRAS could prevent or treat disorders with abnormal bone loss.

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

MeSH terms

  • Animals
  • Bone Resorption / prevention & control*
  • Cathepsin K / genetics
  • Cathepsin K / metabolism
  • Cell Differentiation / drug effects
  • Inflammation / prevention & control*
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Lipopolysaccharides / toxicity
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Mice, Inbred ICR
  • NFATC Transcription Factors / genetics
  • NFATC Transcription Factors / metabolism
  • Osteogenesis / drug effects*
  • Plant Extracts / pharmacology*
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / metabolism
  • RANK Ligand / genetics
  • RANK Ligand / metabolism
  • RAW 264.7 Cells
  • Tartrate-Resistant Acid Phosphatase / genetics
  • Tartrate-Resistant Acid Phosphatase / metabolism
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Interleukin-1beta
  • Lipopolysaccharides
  • NFATC Transcription Factors
  • Nfatc1 protein, mouse
  • Plant Extracts
  • Proto-Oncogene Proteins c-fos
  • RANK Ligand
  • Tnfsf11 protein, mouse
  • Tumor Necrosis Factor-alpha
  • Acp5 protein, mouse
  • Tartrate-Resistant Acid Phosphatase
  • Cathepsin K
  • Ctsk protein, mouse
  • Matrix Metalloproteinase 2
  • Mmp2 protein, mouse
  • Matrix Metalloproteinase 9
  • Mmp9 protein, mouse