Diterpenoids from the aerial parts of Flueggea acicularis and their activity against RANKL-induced osteoclastogenesis

Bioorg Chem. 2020 Jan:94:103453. doi: 10.1016/j.bioorg.2019.103453. Epub 2019 Nov 23.

Abstract

Compounds 1-11 were isolated from the aerial parts of Flueggea acicularis Croizz Webster, including three new rearranged clesistanthane diterpenoids fluacinoids A-C (1-3) and five new norditerpenoid fluacinoids D-H (4-8). The new compounds were identified from spectroscopic data combined with single crystal X-ray diffraction analysis, modified Mosher's methods, and ECD data analyses. All the isolated compounds were evaluated for their activities on RANKL-induced osteoclastogenesis in bone marrow monocytes (BMMs). Compound 6 showed the most potent inhibition against osteoclast differentiation (IC50, 0.7 μM) and decreased the expression level of osteoclast-related genes. Moreover, compound 6 prompted the apoptosis of osteoclasts. Compound 6 also suppressed RANKL-induced NF-κB activation. This study reveals that norditerpenoids may be resource for anti-osteoporosis agents.

Keywords: Clesistanthane diterpenoids; Flueggea acicularis; Osteoclast; Osteoclastogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Diterpenes / chemistry
  • Diterpenes / isolation & purification
  • Diterpenes / pharmacology*
  • Dose-Response Relationship, Drug
  • Euphorbiaceae / chemistry*
  • Mice
  • Mice, Inbred C57BL
  • Molecular Structure
  • Osteoclasts / drug effects
  • Osteoclasts / metabolism
  • Osteogenesis / drug effects*
  • Plant Components, Aerial / chemistry*
  • RANK Ligand / antagonists & inhibitors*
  • RANK Ligand / metabolism
  • RAW 264.7 Cells
  • Structure-Activity Relationship

Substances

  • Diterpenes
  • RANK Ligand
  • Tnfsf11 protein, mouse