• BMB Reports
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• v.51 no.7
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• pp.356-361
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• 2018

Actin-binding LIM protein 1 (ABLIM1), a member of the LIM-domain protein family, mediates interactions between actin filaments and cytoplasmic targets. However, the role of ABLIM1 in osteoclast and bone metabolism has not been reported. In the present study, we investigated the role of ABLIM1 in the receptor activator of $NF-{\kappa}B$ ligand (RANKL)-mediated osteoclastogenesis. ABLIM1 expression was induced by RANKL treatment and knockdown of ABLIM1 by retrovirus infection containing Ablim1-specific short hairpin RNA (shAblim1) decreased mature osteoclast formation and bone resorption activity in a RANKL-dose dependent manner. Coincident with the downregulated expression of osteoclast differentiation marker genes, the expression levels of c-Fos and the nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), critical transcription factors of osteoclastogenesis, were also decreased in shAblim1-infected osteoclasts during RANKL-mediated osteoclast differentiation. In addition, the motility of preosteoclast was reduced by ABLIM1 knockdown via modulation of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt/Rac1 signaling pathway, suggesting another regulatory mechanism of ABLIM1 in osteoclast formation. These data demonstrated that ABLIM1 is a positive regulator of RANKL-mediated osteoclast formation via the modulation of the differentiation and PI3K/Akt/Rac1-dependent motility.

• The Korea Journal of Herbology
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• v.35 no.3
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• pp.17-24
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• 2020

Objectives : The objective of this study was to evaluate the gastric protective effect of Curcuma Longae Rhizoma (CLR) in 150 mM HCl/60% ethanol induced gastric ulcer (GU) in mice. Methods : Forty ICR mice were divided into five groups (n=8/Group): Nor group; Normal, Veh group; GU control, SC group; GU + sucralfate 10 mg/kg, CL; GU + CLR 30% ethanol extract 100 mg/kg, CH group; GU + CLR 30% ethanol extract 200 mg/kg. Then, mice were orally administered with 150 mM HCl/60% ethanol and caused GU. After 1 hr, mice were sacrificed, and blood and stomach tissue were collected. Results : CLR showed significance scavenging effects in 1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis-3-ethyl-benzothiazoline-6-sulfonic acid (ABTS) radical scavenging activities (DPPH IC₅₀; 78.18 ± 0.60 ㎍/㎖, ABTS IC₅₀; 55.91 ± 1.86 ㎍/㎖). CLR significance reduce inflammatory-related factors such as cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin-6 (IL-6) via nuclear factor kappa B (NF-κB) inactivation. In addition, the activation of nuclear factor erythroid2-related factor 2 (Nrf2) significantly led to up-regulation of anti-oxidant enzymes including factors heme oxygenase-1 (HO-1), super oxide dismutase (SOD), and glutathione peroxidase-1/2 (GPx-1/2). Conclusions : Our discovery provides that CLR possesses anti-oxidant and anti-inflammatory effects. Hence, CLR may ameliorate the development of gastric ulcer though the inhibition of NF-κB inflammatory pathway and the elevation of Nrf2 anti-oxidant pathway.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.6
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• pp.1008-1013
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• 2011

Osteoporosis is the leading underlying cause of fractures, particularly in postmenopausal women, due to the loss of estrogen-mediated suppression of bone resorption. More than 50% of adults 50 years of age or older are estimated to have osteoporosis. Osteoclast which is main target for treatment of osteoporosis is originated from hematopoietic cell line. Aloe has been widely used in worldwide country as a coadjuvant medicine. Extracts of the leaves of Aloe have been used in condition to improve dermatologic problem such as seborrheic dermatitis, aphthous stomatitis, xerosis, lichen planus and has been known to exert anti-inflammatory, anti-oxidant and anti-tumor effects. However, despite the popularity of aloe as a plant food supplements, the evaluation of its efficacy as a possible therapeutic option for osteoporosis remains scarce. Thus, we evaluated the effect of Aloe on receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL)-induced osteoclast differentiation. Here we found that Aloe significantly inhibited osteoclast differentiation induced by RANKL. Aloe suppressed the activation of p38 pathway and $NF{\kappa}B$ in bone marrow macrophages (BMMs) treated with RANKL. Also, Aloe significantly inhibited the mRNA expression of c-Fos, tartrate-resistant acid phosphatase (TRAP), osteoclast-associated receptor (OSCAR), nuclear factor of activated T cells (NFAT)c1 and cathepsin K in BMMs treated with RANKL. Particularly, Aloe greatly inhibited the protein expression of c-fos and NFATc1. Taken together, our results suggested that Aloe may be useful tool for treatment of osteoporosis by inhibition of osteoclast differentiation.

• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.2
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• pp.160-165
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• 2012

Osteoporotic fracture became a serious social problem, which related with mortality and morbidity in old age population. Osteoclast which is responsible for bone resorption is originated from hematopoietic cell line and plays a key role osteoporotic bone loss. Cynanchum wilfordii (Asclepiadaceae) roots have been used in Korean folk medicine for the treatment of diabetes mellitus and aging progression. Also, recent studies have shown that the extract and fractions of Cynanchi Wilfordii Radix have various pharmacological actions including scavenging free radicals, enhancing immunity, reducing high serum cholesterol, and anti-tumor activity. However, the effect of extract of Cynanchi Wilfordii Radix in osteoclast differentiation had not been reported. Thus, we evaluated the effect of Cynanchi Wilfordii Radix on receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL)-induced osteoclast differentiation. Through our study, we found that Cynanchi Wilfordii Radix significantly inhibited osteoclast differentiation induced by RANKL. Cynanchi Wilfordii Radix suppressed the activation of p38 pathway and $NF{\kappa}B$ in bone marrow macrophages (BMMs) treated with RANKL. Also, Cynanchi Wilfordii Radix significantly inhibited the mRNA expression of c-Fos, tartrate-resistant acid phosphatase (TRAP), osteoclast-associated receptor (OSCAR), nuclear factor of activated T cells (NFAT)c1 and cathepsin K in BMMs treated with RANKL. Particularly, Cynanchi Wilfordii Radix inhibited the protein expression of c-fos and NFATc1. Taken together, our results demonstrated that Cynanchi Wilfordii Radix may be useful treatment option of bone-related disease such as osteoporosis leads to fracture of bone and rheumatoid arthritis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.27 no.4
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• pp.431-436
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• 2013

Bone homeostasis is maintained by co-ordination of bone-resorbing osteoclasts and bone-forming osteoblasts. Imbalance between osteoclasts and osteoblasts leads to many bone diseases such as osteoporosis, rheumatoid arthritis. Taxillus chinensis is a herb that has been widely used to improve bone health. However, the effect and mechanism of Taxillus chinensis extract on osteoclast differentiation and bone resportion has been unknown. Thus, We investigated the effect of Taxillus chinensis on expression of receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL)-induced osteoclast differentiation and bone resorption. Also, the action of Taxillus chinensis on mechanisms relating to osteoclast differentiation was studied. In this results, we identified that Taxillus chinensis significantly inhibited RANKL-induced osteoclast differentiation and bone resportion. Moreover, Taxillus chinensis was suppressed the activation of NF-${\kappa}B$ in bone marrow macrophage treated RANKL and M-CSF. Taxillus chinensis was down-regulated the mRNA expression of c-Fos, nuclear factor of activated T-cells (NFAT)c1, osteoclast-associated receptor (OSCAR), tartrate-resistant acid phosphatase (TRAP). The cell adhesion-related molecules such as integrin ${\alpha}v$ and integrin ${\beta}3$, and the filamentous actin (F-actin) rings of mature osteoclasts-related molecules such as dendritic cell-specific transmembrane preotein (DC-STAMP) and cathepsin K are also suppressed. Taken together, these results indicated that Taxillus chinensis will be a good candidate to treat osteoclast-mediated bone diseases.

• Nutrition Research and Practice
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• v.17 no.5
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• pp.899-916
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• 2023

BACKGROUND/OBJECTIVES: Oxidative stress is a fundamental neurodegenerative disease trigger that damages and decimates nerve cells. Neurodegenerative diseases are chronic central nervous system disorders that progress and result from neuronal degradation and loss. Recent studies have extensively focused on neurodegenerative disease treatment and prevention using dietary compounds. Heseperetin is an aglycone hesperidin form with various physiological activities, such as anti-inflammation, antioxidant, and antitumor. However, few studies have considered hesperetin's neuroprotective effects and mechanisms; thus, our study investigated this in hydrogen peroxide (H₂O₂)-treated SH-SY5Y cells. MATERIALS/METHODS: SH-SY5Y cells were treated with H₂O₂ (400 µM) in hesperetin absence or presence (10-40 µM) for 24 h. Three-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assays detected cell viability, and 4',6-diamidino-2-phenylindole staining allowed us to observe nuclear morphology changes such as chromatin condensation and apoptotic nuclei. Reactive oxygen species (ROS) detection assays measured intracellular ROS production; Griess reaction assays assessed nitric oxide (NO) production. Western blotting and quantitative polymerase chain reactions quantified corresponding mRNA and proteins. RESULTS: Subsequent experiments utilized various non-toxic hesperetin concentrations, establishing that hesperetin notably decreased intracellular ROS and NO production in H₂O₂-treated SH-SY5Y cells (P < 0.05). Furthermore, hesperetin inhibited H₂O₂-induced inflammation-related gene expression, including interluekin-6, tumor necrosis factor-α, and nuclear factor kappa B (NF-κB) p65 activation. In addition, hesperetin inhibited NF-κB translocation into H₂O₂-treated SH-SY5Y cell nuclei and suppressed mitogen-activated protein kinase protein expression, an essential apoptotic cell death regulator. Various apoptosis hallmarks, including shrinkage and nuclear condensation in H₂O₂-treated cells, were suppressed dose-dependently. Additionally, hesperetin treatment down-regulated Bax/Bcl-2 expression ratios and activated AMP-activated protein kinase-mammalian target of rapamycin autophagy pathways. CONCLUSION: These results substantiate that hesperetin activates autophagy and inhibits apoptosis and inflammation. Hesperetin is a potentially potent dietary agent that reduces neurodegenerative disease onset, progression, and prevention.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.4
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• pp.613-618
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• 2016

1,2,3,4,6-Penta-O-galloyl-${\beta}$-D-glucose (PGG) is a gallotannin isolated from various plants such as Galla Rhois. In a previous study, it was reported that PGG has anti-allergic effects by inhibiting interleukin (IL)-4 signaling in B cells. However, the effect of PGG on basophilic cells remains unclear. Therefore, the aim of this study was to investigate the inhibitory effect of PGG on mitogen and calcium ionophore-induced allergic responses. PGG had no effect on proliferation and cytotoxicity of RBL-2H3 cells. PGG significantly suppressed cell degranulation (histamine and ${\beta}-hexosaminidase$) as well as inflammatory cytokine production such as IL-4 and tumor necrosis factor-${\alpha}$. The underlying mechanism of PGG on these anti-allergic actions was correlated with inhibition on translocation of nuclear factor-${\kappa}B$ from the cytosol to nucleus. These data suggest that PGG is a potentially effective functional compound for prevention of allergic diseases.

• Molecules and Cells
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• v.37 no.9
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• pp.685-690
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• 2014

Osteoclasts are large polykaryons that have the unique capacity to degrade bone and are generated by the differentiation of myeloid lineage progenitors. To identify the genes involved in osteoclast development, we performed microarray analysis, and we found that carboxypeptidase E (CPE), a prohormone processing enzyme, was highly upregulated in osteoclasts compared with their precursors, bone marrow-derived macrophages (BMMs). Here, we demonstrate a novel role for CPE in receptor activator of NF-${\kappa}B$ ligand (RANKL)-induced osteoclast differentiation. The overexpression of CPE in BMMs increases the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinuclear osteoclasts and the expression of c-Fos and nuclear factor of activated T cells c1 (NFATc1), which are key regulators in osteoclastogenesis. Furthermore, employing CPE knockout mice, we show that CPE deficiency attenuates osteoclast formation. Together, our data suggest that CPE might be an important modulator of RANKL-induced osteoclast differentiation.

• 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.

• Korean Journal of Plant Resources
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• v.36 no.1
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• pp.15-25
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• 2023

Myriophyllum spicatum L. has been used as an ornamental in ponds and aquariums, and as a folk remedy for inflammation and pus. Nevertheless, the biological activity and underlying mechanisms of anti-inflammatory effects are unclear. This study is aimed at investigating the antioxidative and anti-inflammatory activities of ethanol extract of Myriophyllum spicatum L. (EMS) in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Antioxidant activity of EMS was assessed by radical-scavenging effects on ferric reducing antioxidant power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals. As inflammatory response parameters produced by LPS-stimulated RAW 264.7 cells were quantified to assess the anti-inflammatory activity of EMS. Our results showed that EMS increased FRAP and DPPH radical-scavenging activity. In EMS-treated RAW 264.7 cells, the production of NO, PGE₂, TNF-α and IL-1β was significantly inhibited at the non-cytotoxic concentration. In addition, EMS significantly attenuated LPS-stimulated the toll-like receptor (TLR) 4/myeloid differentiation protein (MyD) 88 signaling pathway, and inhibited nuclear translocation of nuclear factor-kappa B(NF-κB). Positive correlations were noted between anti-inflammatory activity and antioxidant activity. In conclusion, it was indicated that EMS suppresses the transcription of inflammatory factors by inhibiting the TLR4/MyD88/NF-κB signaling pathway, thereby suppressing LPS-stimulated inflammation in RAW 264.7 cells. This study highlights the potential role of EMS against inflammation and associated diseases.