• Korean Journal of Plant Resources
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• v.27 no.6
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• pp.593-600
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• 2014

Osteoporosis is a progressive bone disease characterized by low bone mass which is caused by disturbance in the balance between the activities of osteoblasts and osteoclasts. Postmenopausal osteoporosis is one of the most common disorders in women after menopause, which is linked to an estrogen deficiency and characterized by an excessive loss of trabecular bone. Rubus coreanus has been used for their various pharmacological properties in Asia as a traditional medicine. To investigate the effect of unripe fruits of R. coreanus 30% ethanol extract (RCE) on osteoblast-like cells (MG63) differentiation, we examined the effects of RCE on in vitro osteoblastic differentiation markers, alkaline phosphatase (ALP) activity and receptor activator of nuclear factor ${\kappa}$-B ligand (RANKL) and osteoprotegerin (OPG) expression. The high concentration (50 and $100{\mu}g/mL$) of RCE markedly increased ALP activity, whereas decreased the RANKL/OPG. We also investigated the effect of RCE on M-CSF plus RANKL-induced differentiation of pre-osteoclast cells (RAW 264.7). RCE treatment remarkably inhibited M-CSF/RANKL-induced formation of osteoclast-like multinuclear cells from RAW 264.7 cells. Moreover, the inhibitory effect of RCE was reduced by selective estrogen receptor-${\alpha}$ antagonist. Our research suggests that suggested that unripe fruits of R. coreanus may act beneficial effects on bone mass by regulating both osteoblast and osteoclast.

• Molecules and Cells
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• v.40 no.5
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• pp.371-377
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• 2017

Despite the importance of the receptor activator of nuclear factor (NF)-kappaB ligand (RANKL)-RANK signaling mechanisms on osteoclast differentiation, little has been studied on how RANK expression is regulated or what regulates its expression during osteoclastogenesis. We show here that insulin signaling increases RANK expression, thus enhancing osteoclast differentiation by RANKL. Insulin stimulation induced RANK gene expression in time- and dose-dependent manners and insulin receptor shRNA completely abolished RANK expression induced by insulin in bone marrow-derived monocyte/macrophage cells (BMMs). Moreover, the addition of insulin in the presence of RANKL promoted RANK expression. The ability of insulin to regulate RANK expression depends on extracellular signal-regulated kinase 1/2 (ERK1/2) since only PD98059, an ERK1/2 inhibitor, specifically inhibited its expression by insulin. However, the RANK expression by RANKL was blocked by all three mitogen-activated protein (MAP) kinases inhibitors. The activation of RANK increased differentiation of BMMs into tartrate-resistant acid phosphatase-positive ($TRAP^+$) osteoclasts as well as the expression of dendritic cell-specific transmembrane protein (DC-STAMP) and d2 isoform of vacuolar ($H^+$) ATPase (v-ATPase) Vo domain (Atp6v0d2), genes critical for osteoclastic cell-cell fusion. Collectively, these results suggest that insulin induces RANK expression via ERK1/2, which contributes to the enhancement of osteoclast differentiation.

• Journal of Physiology & Pathology in Korean Medicine
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• v.33 no.3
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• pp.169-174
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• 2019

The purpose of this study was to evaluate the inhibitory effects of Juglans regia complex extract(JCE) consisted of Juglans regia, Eucommia ulmoides, Eleutherococcus senticosus and Zingiber officinale on osteoclast differentiation. Cell toxicity test by using CCK-8, TRAP activity and TRAP positive multi-nucleated cell counting were performed to evaluate inhibitory effect on differentiation of osteoclast from bone marrow derived macrophages(BMMs) induced by receptor activator of nuclear $factor-{\kappa}B$ ligand(RANKL). As a result, JCE inhibited RANKL-induced osteoclast differentiation in BMMs dose-dependently without cytotoxicity. These results suggest that JCE may have a potential role for treating bone lytic diseases such as osteoporosis.

• Journal of Microbiology and Biotechnology
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• v.31 no.6
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• pp.765-774
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• 2021

Although research on the osteal signaling pathway has progressed, understanding of gut microbial-dependent signaling pathways for metabolic and immune bone homeostasis remains elusive. In recent years, the study of gut microbiota has shed light on our understanding of bone homeostasis. Here, we review microbiota-mediated gut-bone crosstalk via bone morphogenetic protein/SMADs, Wnt and OPG/receptor activator of nuclear factor-kappa B ligand signaling pathways in direct (translocation) and indirect (metabolite) manners. The mechanisms underlying gut microbiota involvement in these signaling pathways are relevant in immune responses, secretion of hormones, fate of osteoblasts and osteoclasts and absorption of calcium. Collectively, we propose a signaling network for maintaining a dynamic homeostasis between the skeletal system and the gut ecosystem. Additionally, the role of gut microbial improvement by dietary intervention in osteal signaling pathways has also been elucidated. This review provides unique resources from the gut microbial perspective for the discovery of new strategies for further improving treatment of bone diseases by increasing the abundance of targeted gut microbiota.

• Journal of Microbiology and Biotechnology
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• v.32 no.2
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• pp.205-211
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• 2022

Probiotics can effectively modulate host immune responses and prevent gastrointestinal diseases. The objective of this study was to investigate the probiotic characteristics of Lactobacillus brevis KU15152 isolated from kimchi and its protective potential against intestinal inflammation induced by Staphylococcus aureus lipoteichoic acid (aLTA). L. brevis KU15152 exhibited a high survival rate in artificial gastric and bile environments. Additionally, the adhesion capability of the strain to HT-29 cells was higher than that of L. rhamnosus GG. L. brevis KU15152 did not produce harmful enzymes, such as β-glucuronidase, indicating that it could be used as a potential probiotic. The anti-inflammatory potential of L. brevis KU15152 was determined in HT-29 cells. Treatment with L. brevis KU15152 suppressed the production of interleukin-8 without inducing significant cytotoxicity. The downregulatory effects of L. brevis KU15152 were involved in the suppression of nuclear factor-kappa B activation mediated by the extracellular signal-regulated kinase and Akt signaling pathways. Collectively, these data suggest that L. brevis KU15152 can be used in developing therapeutic and prophylactic products to manage and treat aLTA-induced intestinal damage.

• Proceedings of the Korean Environmental Sciences Society Conference
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• 2020.10a
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• pp.220-220
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• 2020

Astaxanthin, a natural carotenoid component of shrimp, has been used as a food additive for the treatment of various diseases, but a functional role of Astaxanthin Nanosphere (AN) in the regulation of intestinal mucin (Muc) 2 production during bacterial infection has not described yet. In this study, we have investigated the effect of AN prepared from astaxanthin during Muc2 repression elicited by the Gram-negative bacterium V. vulnificus in human gastrointestinal epithelial (HT-29) cells. AN significantly inhibited the level of ROS production and PKC activation in recombinant protein (r) VvpE-stimulated HT-29 cells. Moreover, AN inhibited the PKC-mediated phosphorylation of extracellular signal-regulated kinase and nuclear factor-kappa B responsible for region-specific hypermethylation in the Muc2 promoter in rVvpE-treated HT-29 cells. In the mouse models of V. vulnificus infection, treatment with AN maintained the level of Muc2 expression in the intestine. On the basis of these results, we suggest that AN blocks the hypermethylation of the Muc2 promoter to restore the level of Muc2 production in HT-29 cells infected with V. vulnificus.

• Proceedings of the Korean Environmental Sciences Society Conference
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• 2020.10a
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• pp.221-221
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• 2020

Curcumin, a hydrophobic polyphenol derived from turmeric, has been used a food additive and as a herbal medicine for the treatment of various diseases. In the present study, we found the functional role of a nanosphere loaded with curcumin (CN) in the promotion of the motility of human umbilical cord blood derived mesenchymal stem cells (hUCB-MSCs) during the wound closure. We found that the efficacy of hUCB-MSCs migration induced by CN was 1000-fold higher than that of curcumin powder. CN significantly increased the motility of hUCB-MSCs by activating c-Src, which is responsible for the phosphorylation of protein kinase C (PKC) and extracellular signal-regulated kinase (ERK). CN induced the expression levels of α-actinin-1, profilin-1 and filamentous-actin, as regulated by the phosphorylation of nuclear factor-kappa B during its promotion of cell migration. In a mouse skin excisional wound model, we found that transplantation of UCB-MSCs pre-treated with CN enhances wound closure, granulation, and re-epithelialization at mouse skin wound sites. These results indicate that CN is a functional agent that promotes the mobilization of UCB-MSCs for cutaneous wound repair.

• Korean Journal of Plant Resources
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• v.31 no.5
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• pp.466-477
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• 2018

In this study, the anti-inflammatory activities of the extracts of different parts of Hovenia dulcis such as leaves, stems, and roots were investigated. Among them, the roots extract (RE) showed the most potent suppressive effect against pro-inflammatory mediators in LPS-stimulated mouse macrophage cells. RE induced dose-dependent reduction of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and concomitantly reduced the production of NO and $PGE_2$. Additionally, pre-treatment with RE significantly suppressed the production of inflammatory cytokines, such as tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), interleukin $(IL)-1{\beta}$, and IL-6, as well as mRNA levels. Moreover, phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear translocation of nuclear factor-kappa B (NF-kB) were also strongly attenuated by RE in RAW264.7 cell. Furthermore, RE induced HO-1 expression through nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and increase HO-1 activity in RAW264.7 macrophages. Therefore, these results indicate that RE strongly inhibits LPS-induced inflammatory responses by blocking NF-kB activation, inhibiting MAPKs phosphorylation, and enhancing HO-1 expression in macrophages, suggesting that RE of H. dulicis and a major component, 27-O-protocatechuoylbetulinic acid could be applied as a valuable natural anti-inflammatory material.

• Korean Journal of Food Science and Technology
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• v.50 no.4
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• pp.437-443
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• 2018

Activation of macrophages plays an important role in the host-immune system. In this study, we investigated the functional roles and related signaling mechanism of hot-water extracts of bee pollen (BPW) in RAW 264.7 macrophages. Since BPW did not exert cytotoxicity at concentrations ranging from 62.5 to $250{\mu}g/mL$ in macrophage cells, a concentration of $250{\mu}g/mL$ was used as the maximum dose of BPW throughout subsequent experiments. BPW increased inducible nitric oxide synthase-mediated nitric oxide production in a concentration-dependent manner. Additionally, BPW was found to induce macrophage activation by augmenting the expression of cell surface molecules (cluster of differentiation; CD80/86, and major histocompatibility complex; MHC class I/II) and production of pro-inflammatory cytokines (tumor necrosis $factor-{\alpha}$, interleukin-6, and $IL-1{\beta}$) through mitogen-activated protein kinase and nuclear $factor-{\kappa}B$ signaling pathways in RAW 264.7 macrophages. Taken together, our results indicate that BPW could potentially be used as an immunomodulatory agent.

• Biomedical Science Letters
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• v.14 no.3
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• pp.147-155
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• 2008

In previous works, we found that solvent extract of Opuntia humifusa Raf., a member of the lactaceae family, displayed potent anti-oxidative and anti-inflammatory activities. Thus, all solvent fractions, except for the water layer, showed potent scavenging effects. According to activity-guided fractionation, one of active radical scavenging principles in the ethyl acetate fraction was found to be taxifolin. In this study, we investigated whether taxifolin showed anti-oxidative activity. In addition, taxifolin modulated nitric oxide (NO) release and the expression of pro-inflammatory cytokine mRNA such as interleukin-$1{\beta}$ (IL-$1{\beta}$), IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), and TNF-${\alpha}$. Taxifolin showed potent anti-oxidant activity with the $IC_{50}\;of\;8.5{\pm}1.4\;and\;9.3{\pm}1.0{\mu}M$ using xanthine/xanthine oxidase (XO) assay and 2,2-Diphenyl-lpicrylhydrazyl radical (DPPH) assay, respectively. We next determined the role of taxifolin on the immunomodulating activity using murine macrophage cell line RAW264.7 cells. Taxifolin dose-dependently inhibited NO production in lipopolysaccharide (LPS)-activated RAW264.7. It also significantly blocked the expression of inducible NO synthase (iNOS) mRNA in the LPS-stimulated RAW264.7 cells. In addition, taxifolin potently suppressed the expression of IL-$1{\beta}$, IL-6 and GM-CSF mRNA in LPS-activated RAW264.7 cells, but not that of TNF-${\alpha}$ Moreover, taxifolin significantly inhibited the transcriptional activity of nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and activator protein -1 (AP-1). These results suggest that taxifolin may downregulate inflammatory iNOS, IL-$1{\beta}$, IL-6 and GM-CSF gene expressions through inhibition of NF-K and AP-1 activation in LPS-stimulated RAW264.7 cells.