Abstract
Vigeo is a mixture of fermented extracts of Eleutherococcus senticosus Maxim (ESM), Achyranthes japonica (Miq.) Nakai (AJN), and Atractylodes japonica Koidzumi (AJK) manufactured using the traditional Korean nuruk fermentation method. Although the bioactive effects of ESM, AJN, and AJK have already been reported, the pharmacological effects of Vigeo have not been proven. Therefore, in this study, we investigated whether Vigeo had inhivitory effects on lipopolysaccharide (LPS)-induced inflammatory bone loss in vivo and receptor activator of nuclear factor-B ligand (RANKL)-induced osteoclastogenesis and the related mechanism in vitro. Vigeo administration conferred effective protection against bone loss induced by excessive inflammatory response and activity of osteoclasts in LPS-induced inflammatory osteoporosis mouse model. In addition, Vigeo significantly suppressed the formation of tartrate-resistant acid phosphatase-positive osteoclasts induced by RANKL and inhibited F-actin formation and bone resorbing activity without any cytotoxicity. Moreover, Vigeo significantly inhibited RANKL-induced phosphorylation of p38, ERK, JNK, IκB, and AKT and degradation of IkB. Additionally, Vigeo strongly inhibited the mRNA and protein expression of c-FOS and NFATc1 and subsequently attenuated the expression of osteoclast specific marker genes induced by RANKL. We demonstrated for the first time the anti-osteoporosis effect of Vigeo, suggesting that it could be a potential therapeutic candidate for the treatment of osteoclast-mediated inflammatory bone diseases.
Highlights
Osteoporosis is a common disease caused by problems with the bone remodeling process and is characterized by a reduction in bone mass and bone microstructural alterations [1]
Vigeo inhibited the RANKL-induced increase in the mRNA expression of DC-cstamp, OC-stamp, αv-integrin, β3 -integrin, Atp6v0d2, and Cathepsin K (Ctsk) at 48 h (Figure 6). These results demonstrate that Vigeo inhibited RANKL-induced osteoclastogenesis through de-phosphorylation of AKT, JNK, p38, ERK, and IκB, followed by downregulation of transcription factors
We demonstrated for the first time that Vigeo, a functional extract using the traditional nuruk fermentation method, can inhibit RANKL-induced osteoclastogenesis by blocking the AKT, NF-κB and MAPK signaling pathways in vitro and prevent bone loss in vivo in an LPS-triggered bone loss mouse model
Summary
Osteoporosis is a common disease caused by problems with the bone remodeling process and is characterized by a reduction in bone mass and bone microstructural alterations [1]. In order to counteract the side effects of osteoporosis drugs currently in use, many researchers have tried to develop new treatments for bone metabolic disorders based on natural plant-derived compounds. The use of plants for treatment of several diseases has a long history [2,3]. Fermentation with plant products may further enhance the functional properties of medicinal plants or attenuate their toxicity and side effects [6,7]. Complex substances are broken down into smaller molecules by microorganisms to generate stable products, which improves their pharmacological efficacy for disease prevention [8]
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