Water extract of Magnolia officinalis cortex inhibits osteoclastogenesis and bone resorption by downregulation of nuclear factor of activated T cells cytoplasmic 1

Abstract

BackgroundMagnolia officinalis cortex has been traditionally used to treat stomach and intestine diseases in traditional Korean medicine. In this study, we investigated the effect of water extract of M. officinalis cortex (WEMC) on osteoclast differentiation and function.MethodsPhytochemical characterization of WEMC was performed by high-performance liquid chromatography analysis. Osteoclast differentiation of bone marrow-derived macrophages was determined by tartrate-resistant acid phosphatase activity assay. Receptor activator of nuclear factor-κB ligand (RANKL) signaling factors and transcription factors regulating osteoclast differentiation were analyzed by Western blot and real-time polymerase chain reaction. Bone resorption function of mature osteoclasts was examined by using culture plate coated with inorganic crystalline calcium phosphate. Furthermore, the in vivo effect of WEMC on osteoporosis was examined using RANKL-induced bone loss model, characterized by micro-computed tomography and bone metabolism marker analysis.ResultsWEMC inhibited RANKL-induced osteoclast differentiation and the bone resorbing activity of mature osteoclasts. WEMC contains gallic acid and honokiol as active constituents contributing to the inhibitory effect of WEMC on osteoclast differentiation. Further, WEMC suppressed RANKL-induced activation of p38 and nuclear factor-κB pathways and expression of osteoclastogenic transcription factors such as c-Fos for AP-1 and nuclear factor of activated T cells cytoplasmic 1. Ectopic overexpression of a constitutive active form of nuclear factor of activated T cells cytoplasmic 1 rescued the antiosteoclastogenic effect of WEMC. Consistent with the in vitro results, WEMC suppressed RANKL-induced trabecular bone loss in mice.ConclusionWEMC might have a therapeutic potential to treat pathological bone diseases due to increased osteoclast differentiation and function.

Polyphenolic Compounds Inhibit Osteoclast Differentiation While Reducing Autophagy through Limiting ROS and the Mitochondrial Membrane Potential

“…As bioactive polyphenolic compounds provide enormous health benefits with their antioxidant and anti-inflammatory properties [ 37 ], a new field of interest has emerged involving osteo-immune-oncology, bone metabolism, and tumorigenesis [ 5 , 6 , 9 , 12 , 38 ]. The data we have collected is in agreement with much of the previous literature on the interactions between polyphenolic compounds and osteoclastogenesis [ 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ]. Antioxidant properties are well-studied for EA, GA, and TA [ 37 , 47 , 48 ], which is why we have chosen those molecules for the immune modulation of monocytes in our current study.…”

A Double-Blind Placebo-Controlled Randomized Trial Evaluating the Effect of Polyphenol-Rich Herbal Congee on Bone Turnover Markers of the Perimenopausal and Menopausal Women

“…Recent finding has demonstrated that polyphenolic compounds inhibit receptor activator of nuclear factor- κ B ligand- (RANKL-) induced osteoclast formation [17]. Since the herbal congee containing the combination extract of P. odoratum and M. alba contained high concentration of polyphenol, this substance may possibly be active constituent which contributes a role on an antiosteoclastogenic effect of the herbal congee containing the combination extract of P. odoratum and M. alba .…”

Compounds isolated from Euonymus spraguei Hayata induce ossification through multiple pathways

“…However, a soluble decoy OPG produced by osteoblast binds to RANK, limiting excessive formation of mature osteoclasts ( Martin and Sims, 2015 ). A study showed that 2 inhibited osteoclast formation ( Li et al, 1998 ), and also prevented RANKL-induced osteoclast formation of bone marrow macrophages ( Shim et al, 2015 ). This is in agreement with our study, as our results showed that both 2 and 3 increased the mRNA expression level of OPG and subsequently decreased the level of RANKL, thus elevating the OPG/RANKL ratio ( Fig.…”