Abeliophyllum distichum Nakai alleviates postmenopausal osteoporosis in ovariectomized rats and prevents RANKL-induced osteoclastogenesis in vitro

J Ethnopharmacol. 2020 Jul 15:257:112828. doi: 10.1016/j.jep.2020.112828. Epub 2020 Apr 5.

Abstract

Ethnopharmacological relevance: Abeliophyllum distichum Nakai (AD), called Miseon, is one of Korea's monotypic endemic species. As a folk remedy, the AD has been used to treat inflammatory disease, stomachaches, diarrhea, and gynecologic disease in Korea. Some researchers have reported that the AD has anti-cancer, anti-inflammatory, and anti-oxidant effects. But the protective effect of AD leaf for osteoporosis has not been reported yet.

Aim of the study: This study aimed to analyze the effects and mechanism of AD-ethyl acetate fraction (EA) extract on the osteoporosis, one of the gynecologic disease.

Materials and methods: The RAW 264.7 cells were used as a model for RANKL-induced osteoclastogenesis. We measured the TRAcP activity, expressions of NFATc1, c-fos, and MAPK to investigate the effect of AD-EA. OVX-induced osteoporosis rat model was used as menopausal osteoporosis. After both ovaries were removed through a surgical procedure, and AD-EA or 17b-estradiol was orally administered for 8 weeks. BMD of femurs was measured as well as the bone morphometric parameter, such as BV/TV, trabecular thickness, number and surface using a micro CT.

Results: AD-EA significantly inhibited TRAcP activity, actin ring formation, pit formation and the expressions of osteoclast-related genes in a dose-dependent manner through the inhibition of the MAPK and c-fos/NFATc1 pathway. In addition, low dose administration of AD-EA improved the deterioration of trabecular bone microarchitecture caused by OVX through the inhibition of bone resorption by TRAcP and CTK.

Conclusions: These results suggest that AD-EA may contribute to the therapy of osteoporosis caused by menopause in women.

Keywords: Abeliophyllum distichum Nakai; NFATc-1; Ovariectomized rat; RANKL; c-fos.

MeSH terms

  • Animals
  • Bone Resorption / drug therapy
  • Bone and Bones / pathology
  • Carbonic Anhydrase II / metabolism
  • Cathepsin K / metabolism
  • Femur
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • NFATC Transcription Factors / metabolism
  • Osteoclasts / drug effects
  • Osteogenesis / drug effects*
  • Osteoporosis, Postmenopausal / drug therapy*
  • Ovariectomy*
  • Plant Extracts / pharmacology*
  • RANK Ligand / metabolism*
  • RANK Ligand / pharmacology*
  • RAW 264.7 Cells
  • Rats
  • Rats, Sprague-Dawley
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptors, Cell Surface
  • Republic of Korea
  • Signal Transduction / drug effects
  • TNF Receptor-Associated Factor 6 / metabolism
  • Tartrate-Resistant Acid Phosphatase / blood
  • Tartrate-Resistant Acid Phosphatase / metabolism
  • Vacuolar Proton-Translocating ATPases / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • NFATC Transcription Factors
  • Oscar protein, mouse
  • Plant Extracts
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptors, Cell Surface
  • TNF Receptor-Associated Factor 6
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase Kinases
  • Tartrate-Resistant Acid Phosphatase
  • Cathepsin K
  • Matrix Metalloproteinase 9
  • Vacuolar Proton-Translocating ATPases
  • Carbonic Anhydrase II