Diphlorethohydroxycamalol isolated from Ishige okamurae prevents H2O2-induced oxidative damage via BMP2/Runx2 signaling in osteoblastic MC3T3-E1 cells

Fitoterapia. 2021 Jul:152:104921. doi: 10.1016/j.fitote.2021.104921. Epub 2021 May 11.

Abstract

Accumulating evidence has shown an association between osteoporosis and oxidative damage. In the present study, the protective effects of diphlorethohydroxycarmalol (DPHC) isolated from the brown algae Ishige okamurae against H2O2-induced oxidative damage via bone morphogenetic protein 2 (BMP2)/ runt-related transcription factor 2 (Runx2) signaling were investigated using MC3T3-E1 osteoblastic cells. DPHC counteracted the reduction in cell viability caused by H2O2 exposure and protected against H2O2-induced dysfunction, demonstrated by improved cellular alkaline phosphatase (ALP) activity and calcium deposition. In addition, treatment with 0.05-0.2 mM DPHC elevated the protein expression of osteoblast differentiation factors type 1 collagen, ALP, p-Smad1/5, Osterix, BMP2, and Runx2, in response to H2O2-induced oxidative damage. Importantly, DPHC decreased the expression levels of receptor activator of nuclear factor kappa-B ligand, which promotes bone resorption, and inhibited the H2O2-induced generation of reactive oxygen species. Taken together, the results suggest that DPHC counteracts the effects of oxidative stress in osteoblastic cells and has the potential to be effective in preventing and alleviating osteoporosis.

Keywords: Diphlorethohydroxycarmalol; Osteoblast differentiation; Osteoprotection; Oxidative stress.

MeSH terms

  • 3T3 Cells
  • Animals
  • Bone Morphogenetic Protein 2
  • Cell Differentiation / drug effects
  • Cell Survival / drug effects
  • Core Binding Factor Alpha 1 Subunit
  • Heterocyclic Compounds, 3-Ring / isolation & purification
  • Heterocyclic Compounds, 3-Ring / pharmacology*
  • Hydrogen Peroxide
  • Mice
  • Molecular Structure
  • Osteoblasts / drug effects*
  • Oxidative Stress / drug effects*
  • Phaeophyceae / chemistry*
  • Reactive Oxygen Species / metabolism
  • Republic of Korea
  • Signal Transduction*

Substances

  • Bmp2 protein, mouse
  • Bone Morphogenetic Protein 2
  • Core Binding Factor Alpha 1 Subunit
  • Heterocyclic Compounds, 3-Ring
  • Reactive Oxygen Species
  • Runx2 protein, mouse
  • diphlorethohydroxycarmalol
  • Hydrogen Peroxide