• 한국자원식물학회지
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• 제27권6호
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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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• 제40권5호
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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.

• 동의생리병리학회지
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• 제33권3호
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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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• 제31권6호
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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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• 제32권2호
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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.

• 한국환경과학회:학술대회논문집
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• 한국환경과학회 2020년도 정기학술대회 발표논문집
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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.

• 한국환경과학회:학술대회논문집
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• 한국환경과학회 2020년도 정기학술대회 발표논문집
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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.

• 한국자원식물학회지
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• 제31권5호
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• pp.466-477
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• 2018

본 연구는 헛개나무 잎, 줄기, 뿌리로부터 얻어진 메탄올 추출물의 항염증 효과를 구명하기 위해서 수행되었다. LPS로 염증이 유도된 RAW264.7 세포 내 부위별 추출물을 동시에 처리하여 염증 매개성 물질인 NO 생성량 분석 결과 $40{\mu}g/m{\ell}$농도에서 뿌리(94.7%)와 줄기(42.6%)에서는 효과가 있는 반면 잎에서는 효과가 없는 것으로 확인되었다. 이 중 탁월한 효과를 보인 뿌리 추출물(RE)의 항염증 효과 및 관련 분자적 기전을 확인하였다. 그 결과, 염증 반응의 주요 경로인 NF-kB 및 MAPK 신호전달경로에서 RE가 LPS로 유도된 NF-kB의 핵 이동을 억제하고, ERK, JNK, p38의 인산화를 억제함으로써 iNOS, COX-2의 발현이 감소되고, NO와 pro-inflammatory cytokine (IL-6, $IL-1{\beta}$, $TNF-{\alpha}$)의 생성이 억제됨을 확인하였다. 또한 RE는 대식세포에서 Nrf2를 활성화시켜 항염증성 단백질인 HO-1 발현을 유도하여 항염증 효과를 나타내었다. 또한, RE로부터 주요 성분을 분리한 후 NMR과 MS 기기를 이용하여 구조 동정된 27-O-protocatechuoylbetulinic acid 화합물에서도 높은 항염증 효과를 확인하였다. 이러한 연구결과는 헛개나무뿌리와 그 주요성분은 의약품 소재 및 기능성 식품 등의 기능성 소재로 활용될 수 있는 기초적인 정보를 제공할 것으로 생각된다.

• 한국식품과학회지
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• 제50권4호
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• pp.437-443
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• 2018

본 연구는 꿀벌 꽃가루 열수 추출물(BPW)의 면역 활성에 관하여 알아보기 위하여, 선천면역과 적응면역에서 중심 역할을 수행하는 큰포식세포에 BPW를 처리하여 세포 생존율, NO 분비능, 사이토카인($TNF-{\alpha}$, IL-6, $IL-1{\beta}$) 분비능과 메커니즘 분석을 통한 신호전달에 관하여 관찰하였다. BPW를 큰포식세포에 처리하여 면역활성에 관하여 알아봤을 때, 큰포식세포 면역활성의 대표적인 바이오마커인 NO, 사이토카인의 분비능과 iNOS의 세포내 발현이 BPW 처리구에서 유의적으로 증가되는 것으로 관찰되었다. 또한 활성화된 탐식 세포의 세포 표면에서 발현되는 CD80과 CD86의 발현과 탐식세포의 항원제시에 밀접한 관련이 있는 주조직적합성 복합체(MHC class I과 II)의 발현이 BPW 처리구에서 유의적으로 증가되는 것으로 관찰되었다. 기전분석 결과, BPW의 처리는 MAPKs의 인산화와 $NF-{\kappa}B$의 핵 내 이동성을 증가시켜 면역활성을 증가시키는 것으로 관찰되었다. 따라서 BPW의 처리는 큰포식세포의 활성을 유도시켜 면역활성을 조절하는 것으로 관찰되었다.

• 대한의생명과학회지
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• 제14권3호
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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.