6,7,4′‐Trihydroxyflavone inhibits osteoclast formation and bone resorption in vitro and in vivo

Abstract

The balance between the osteoblasts and the osteoclasts is important for the maintenance of the skeleton of the human body. The osteoclasts absorb bone after differentiated into polymorphonuclear cells by the fusion of monocytes/macrophages. We have found that 6,7,4′‐Trihydroxyflavone (THF), a compound from the heartwood of Dalbergia Odorifera inhibits receptor activator of NF‐κB ligand (RANKL)‐induced osteoclast differentiation, actin ring formation, and bone resorption in RAW 264.7 cells and bone marrow macrophage. THF significantly inhibited the c‐Jun‐N‐terminal kinase signaling pathway without affecting extracellular signal‐regulated kinase, p38, and AKT signaling. Moreover, THF inhibited the expression of c‐Fos, nuclear factor‐activated T cells cytoplasm 1, cathepsin K, and c‐src by RANKL. We used a lipopolysaccharide (LPS)‐induced bone loss model in mice. Consequently, bone volume per tissue volume, trabecular number's reduction was recovered in THF‐treated mice, and trabecular separation's augmentation was also attenuated by THF administration. In summary, THF inhibits RANKL‐induced osteoclast differentiation by MAPK signaling pathway and inhibits bone resorption by destroying the actin ring in mature osteoclasts. THF also prevented LPS‐induced bone loss in a mice model. Thus, THF may be useful in the treatment of bone diseases associated with excessive osteoclast differentiation and bone resorption.

Protective Effects of 6,7,4′-Trihydroxyflavanone on Hypoxia-Induced Neurotoxicity by Enhancement of HO-1 through Nrf2 Signaling Pathway

“…Since it has been previously reported that THF is not cytotoxic to RAW 264.7 cells [15], we first confirmed whether THF shows cytotoxicity in SH-SY5y neuronal cells. Figure 2A shows that treatment with up to 40 µM of THF does not induce cell death.…”

“…2.2. Isolation of 6,7,4'-Tryhydroxyflavanone from Dalbergia Odorifera THF (C 15 H 12 O 5 , Figure 1) was isolated from D. odorifera as previously reported [15]. Briefly, D. odorifera was purchased from the Herbal Medicine Cooperative Association of Jeonbuk Province, Korea.…”

“…In East Asia, including Korea and China, D. odorifera extract has long been used as a therapeutic agent for rheumatic and epigastric pain, blood stagnation syndrome, ischemia, and swelling [14]. Accumulating evidences demonstrate that THF exhibits effective regulation of osteoclastogenesis by controlling bone resorption and protective role against methamphetamine-induced cytotoxicity on T cells [15,16]. In particular, it has been reported that THF effectively suppresses the NF-κB pathway in two studies to possess anti-osteoclastogenesis and cytoprotective effect against methamphetamine exposure.…”

6,7,4′-Trihydroxyflavanone Mitigates Methamphetamine-Induced Neurotoxicity in SH-SY5y Cells via Nrf2/heme Oxyganase-1 and PI3K/Akt/mTOR Signaling Pathways

“…6,7,4′-trihydroxyflavanone (THF, C 15 H 12 O 5 ), a bioactive molecule of the flavanone family, is isolated from Dalbergia odorifera (Leguminosae) [ 23 ] and has been traditionally used for its anti-epigastric pain, anti-rheumatic, anti-ischemic, and anti-swelling properties [ 24 ]. Recent reports have shown that THF possesses several bioactivities against osteoclastogenesis in bone formation, exerting anti-inflammatory effects against dextran sodium sulfate (DSS)-induced immune bowel disease (IBD) and protective effects against hypoxia-induced neurotoxicity via the enhancement of the Nrf2/HO-1 signaling pathway [ 23 , 25 ]. In particular, the ameliorative effect of THF on METH-induced cytotoxicity has been studied in T cells, where pretreatment with THF significantly restored the METH-induced deactivation of T cells under stimulated conditions [ 26 ].…”

Thermosensitive nanoparticle of mPEG-PTMC for oligopeptide delivery into osteoclast precursors

“…It plays an important role in the development, growth, repair, and reconstruction of bone. [1][2][3][4] Although their activity is normally integrated with the requirements of skeletal morphogenesis and remodeling, excessive bone resorption is a major pathological factor in chronic inflammatory diseases. 5,6 In recent years, there is evidence suggesting that inhibiting cellular ossification will be the most effective way to treat chronic diseases.…”