RRC ID 51812
Author Chawalitpong S, Sornkaew N, Suksamrarn A, Palaga T.
Title Diarylheptanoid from Curcuma comosa Roxb. suppresses RANKL-induced osteoclast differentiation by decreasing NFATc1 and c-Fos expression via MAPK pathway.
Journal Eur. J. Pharmacol.
Abstract Osteoporosis is caused by a functional imbalance between osteoblasts and osteoclasts. The increased activation of osteoclasts that is a hallmark of osteoporosis results in the progressive loss of bone mass and therefore in an increased susceptibility to bone fractures. Diarylheptanoids are a group of phytoestrogens that have been isolated from a number of plant species, including the rhizomes of Curcuma comosa Roxb. In this study, the effect of one of diarylheptanoids, (3S)-1-(3,4-dihydroxyphenyl)-3-hydroxy-7-phenyl-(6E)-6-heptene (DHPH), was investigated for anti-inflammatory and anti-osteoclastogenic activity. DHPH significantly inhibited nitric oxide production in RAW264.7 cell line following their activation by lipopolysaccharide and interferon-γ, with no cytotoxicity. In primary mouse bone-marrow-derived macrophage precursors, DHPH suppressed osteoclastogenesis induced by receptor activator of nuclear factor-κB (RANK) ligand at an inhibitory concentration 50 of 325±1.37nM. DHPH treatment delayed and reduced the expression of master regulators of osteoclast differentiation, NFATc1 and c-Fos. Consistent with this result, the mRNA level of cathepsin K, associated with osteoclast differentiation, was decreased whereas the reduction in the mRNA of irf8, a negative regulator of osteoclast differentiation, was similar to that measured in the vehicle-treated control cells. DHPH reduced the phosphorylation of p38 MAPK, ERK (p44/42). Furthermore, DHPH suppressed the bone absorption activity of osteoclasts and enhanced osteoblast differentiation. Taken together, DHPH interrupts the immediate downstream signaling cascade of RANK and interferes with osteoclast differentiation and its function while enhances osteoblast differentiation. These results demonstrate the potential of this diarylheptanoid as a new therapeutic agent in osteoporosis.
Volume 788
Pages 351-359
Published 2016-10-5
DOI 10.1016/j.ejphar.2016.08.012
PII S0014-2999(16)30517-9
PMID 27523282
MeSH Animals Anti-Inflammatory Agents / pharmacology Anti-Inflammatory Agents / therapeutic use Anti-Inflammatory Agents / toxicity Bone Resorption / drug therapy Bone Resorption / metabolism Bone Resorption / pathology Cell Differentiation / drug effects* Curcuma / chemistry Diarylheptanoids / pharmacology* Diarylheptanoids / therapeutic use Diarylheptanoids / toxicity Down-Regulation / drug effects MAP Kinase Signaling System / drug effects* Mice NF-kappa B / metabolism NFATC Transcription Factors / genetics* Osteoclasts / cytology Osteoclasts / drug effects* Osteoclasts / metabolism Osteoclasts / pathology Proto-Oncogene Proteins c-fos / genetics* RANK Ligand / pharmacology* RAW 264.7 Cells
IF 3.04
Human and Animal Cells MC3T3-E1(RCB1126)