A new naphthalene glycoside from Chimaphila umbellata inhibits the RANKL-stimulated osteoclast differentiation

Arch Pharm Res. 2015 Nov;38(11):2059-65. doi: 10.1007/s12272-015-0598-3. Epub 2015 Apr 11.

Abstract

A new naphthalene glycoside was isolated from the leaves and stems of Chimaphila umbellata Barton. Its chemical structure was elucidated to be 2,7-dimethyl-1,4-dihydroxynaphthalene-1-O-β-D-glucopyranoside (DMDHNG), based on spectroscopic evidence. DMDHNG significantly inhibited the receptor activator of nuclear factor-κB ligand (RANKL)-induced tartrate-resistant acid phosphatase (TRAP) activity and the formation of multinucleated osteoclasts in a dose-dependent manner. In addition, the new glycoside inhibited the RANKL-induced mRNA expression of osteoclast-associated genes that encode TRAP, cathepsin K, and another transcription factor-nuclear factor of activated T-cells c1. We believe that the inhibitory effects of DMDHNG on the osteoclast differentiation may be exploited for a therapeutic benefit.

Keywords: 2,7-Dimethyl-1,4-dihydroxynaphthalene-1-O-β-D-glucopyranoside; Chimaphila umbellata; Osteoclast; Receptor activator of nuclear factor-κB ligand; Tartrate-resistant acid phosphatase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Phosphatase / genetics
  • Acid Phosphatase / metabolism
  • Cathepsin K / genetics
  • Cell Differentiation / drug effects*
  • Dose-Response Relationship, Drug
  • Glucosides / administration & dosage
  • Glucosides / isolation & purification
  • Glucosides / pharmacology*
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • NFATC Transcription Factors / genetics
  • Naphthols / administration & dosage
  • Naphthols / isolation & purification
  • Naphthols / pharmacology*
  • Osteoclasts / cytology
  • Osteoclasts / drug effects*
  • Plant Leaves
  • Plant Stems
  • Pyrolaceae / chemistry*
  • RANK Ligand / administration & dosage
  • RNA, Messenger / metabolism
  • Tartrate-Resistant Acid Phosphatase

Substances

  • 2,7-dimethyl-1,4-dihydroxynaphthalene-1-O-glucopyranoside
  • Glucosides
  • Isoenzymes
  • NFATC Transcription Factors
  • Naphthols
  • RANK Ligand
  • RNA, Messenger
  • Acid Phosphatase
  • Tartrate-Resistant Acid Phosphatase
  • Cathepsin K