A novel flavonoid isolated from the steam-bark of Ulmus Wallichiana Planchon stimulates osteoblast function and inhibits osteoclast and adipocyte differentiation

Gaurav Swarnkar, Kunal Sharan, Jawed A. Siddiqui, Bandana Chakravarti, Preeti Rawat, Manmeet Kumar, Kamal R. Arya, Rakesh Maurya, Naibedya Chattopadhyay

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

(2S,3S)-Aromadendrin-6-C-β-d-glucopyranoside (AG) is a novel flavonol isolated from the extract of Ulmus wallichiana (Himalayan Elm). Extract of U. wallichiana is used as a traditional medicine for rapid fracture repair in India. We characterized the mechanism of action of AG in mouse bone cells by investigating its effect on the precursors of osteoblasts, osteoclasts and adipocytes. At nanomolar concentrations, AG increased differentiation of preosteoblasts obtained from neonatal mouse calvaria. The gene expression of osteogenic markers, including runt-related transcription factor 2 (Runx-2), bone morphogenetic protein-2 (BMP-2), type I collagen and osteocalcin were elevated in the preosteoblasts. The extracellular matrix mineralization was higher in preosteoblast and bone marrow cells when AG was present in the medium. Furthermore, AG protected the differentiated osteoblasts from serum deprivation-induced apoptosis, and increased the expression of the anti-osteoclastogenic cytokine, osteoprotegerin. It inhibited osteoclast differentiation of bone marrow precursor cells to osteoclasts in the presence of receptor activator of nuclear factor kappa-B ligand (RANKL) and monocyte/macrophage-colony stimulating factor (M-CSF). Additionally, in 3T3-L1 preadipocytes, AG decreased the expression of genes involved in adipogenesis, including peroxisome proliferator-activated receptor gamma (PPARγ), sterol regulatory element binding protein (SREBP) and CCAAT/enhancer-binding protein alpha (CEBP/α), and induced apoptosis of differentiated adipocytes. Induction of adipogenic differentiation was also inhibited in the presence of AG. AG exhibited no estrogenic/antiestrogenic effect. Together, our data show that AG has potent osteogenic, anti-osteoclastogenic and anti-adipogenic effects, which may translate to a better skeletal outcome in postmenopausal osteoporosis.

Original languageEnglish
Pages (from-to)65-73
Number of pages9
JournalEuropean Journal of Pharmacology
Volume658
Issue number2-3
DOIs
StatePublished - May 11 2011

Keywords

  • Adipogenesis
  • Bone marrow
  • Flavonoid C-glucoside
  • Osteoclastogenesis
  • Osteogenic

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