• Nutrition Research and Practice
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• v.14 no.3
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• pp.175-187
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• 2020

BACKGROUND/OBJECTIVES: In this study, we investigated the beneficial effects of skate cartilage extracts containing chondroitin sulfate (SCS) on hyperlipidemia-induced inflammation and oxidative stress in high cholesterol diet (HCD)-fed mice in comparison with the effects of shark cartilage-derived chondroitin sulfate (CS). MATERIALS/METHODS: Low-density lipoprotein receptor knockout (LDLR-KO) mice were fed HCD with an oral administration of CS (50 and 100 mg/kg BW/day), SCS (100 and 200 mg/kg BW/day), or water, respectively, for ten weeks. RESULTS: The administration of CS or SCS reduced the levels of serum triglyceride (TG), total cholesterol (TC), and LDL cholesterol and elevated the levels of high-density lipoprotein cholesterol, compared with those of the control group (P < 0.05). Furthermore, CS or SCS significantly attenuated inflammation by reducing the serum levels of interleukin (IL)-1β and hepatic protein expression levels of nuclear factor kappa B, inducible nitric oxide synthase, cyclooxygenase-2, and IL-1beta (P < 0.05). In particular, the serum level of tumor necrosis factor-alpha was reduced only in the 100 mg/kg BW/day of SCS-fed group, whereas the IL-6 level was reduced in the 100 and 200 mg/kg BW/day of SCS-fed groups (P < 0.05). In addition, lipid peroxidation and nitric oxide production were attenuated in the livers of the CS and SCS groups mediated by the upregulation of hepatic proteins of antioxidant enzymes, such as superoxide dismutase, catalase, and glutathione peroxidase (P < 0.05). CONCLUSIONS: These results suggest that the biological effects of SCS, similar to those of CS, are attributed to improved lipid profiles as well as suppressed inflammation and oxidative stress induced by the intake of HCD.

• Journal of Periodontal and Implant Science
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• v.32 no.4
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• pp.733-744
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• 2002

The fibroblasts are the principal cells in the periodontal ligament of peridontium. As the periodontal ligament fibroblasts (PDLF) show similar phenotype with osteoblasts, the PDLF are thought to play an important role in alveolar bone remodeling. Cell-to-cell contacted signaling is crucial for osteoclast formation. Recently it has been reported that PDLJ enhance the bone resorbing activity of osteoclasts differentiated from hematopoietic preosteoclasts. The aims of this study were to $clarify\;^{1)}$ the mechanism of PDLF-induced osteoclastogenesis $and\;^{2)}$ whether we can use preosteoclast cell line instead of primary hematopoietic preosteoclast cells for studying the mechanism of PDLF-induced osteoclastogenesis. Osteoclastic differentiation of mouse macrophage cell line RAW264.7 was compared with that of mouse bone marrow-derived M-CSF dependent cell (MDBM), a well-known hematopoietic preosteoclast model, by examining, 1) osteoclast-specific gene expression such as calcitonin receptor, M-CSF receptor (c-fms), cathepsin K, receptoractivator nuclear factor kappa B (RANK) ,2) generation of TRAP(+) multinucleated cells (MNCs), and 3) generation of resorption pit on the $OAAS^{TM}$ plate. RAW264.7 cultured in the medium containing of soluble osteoclast differentiation Factor (sODF) showed similar phenotype with MDBM-derived osteoclasts, those are mRNA expression pattern of osteoclast-specific genes, TRAP(+) MNCs generation, and bone resorbing abivity. Formation of resorption pits by osteoclastic MNCs differentiated from sODF-treated RAW264.7, was completely blocked by the addition of osteoprotegerin (OPG), a soluble decoy receptor for ODF, to the sODF-containing culture me야um. The effects of PDLF on differentiation of RAW264.7 into　the TRAP(+) multinucleated osteoclast-like cells were examined using coculture system. PDLF were fxed with paraformaldehyde, followed by coculture with RAW264.7, which induced formation of TRAP(+) MNCs in the absence of additional treatment of sODF. When compared with untreated and fixed PDLF (fPDLF), IL-1 ${\beta}$-treated, or lipopolysaccha-ride-treated and then fixed PDLF showed two-folld increase in the supporting activity of osteoclastogenesis from RAW264.7 coculture system. There were no TRAP(+) MNCs formation in coculture system of RAW264.7 with PDLF of no fixation. These findigs suggested that we can replace the primary hematopoietic preosteoclasts for RAW264. 7 cell line for studying the mechanism of PDLF-induced osteoclastogenesis, and we hypothesize that PDLF control osteoclastogenesis through ODF expression which might be enhanced by inflammatory signals.

• Journal of Periodontal and Implant Science
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• v.42 no.6
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• pp.185-195
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• 2012

Purpose: (-)-epigallocatechin-3-gallate (EGCG) has been reported to exert anti-inflammatory and antibacterial effects in periodontitis. However, its exact mechanism of action has yet to be determined. The present in vitro study evaluated the anti-in-flammatory effects of EGCG on human periodontal ligament fibroblasts (hPDLFs) and human periodontal ligament stem cells (hPDLSCs) affected by bacterial lipopolysaccharide (LPS) extracted from Porphyromonas gingivalis. Methods: hPDLFs and hPDLSCs were extracted from healthy young adults and were treated with EGCG and/or P. gingivalis LPS. After 1, 3, 5, and 7 days from treatment, cytotoxic and proliferative effects were evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and bromodeoxyuridine assay, respectively. And then, the gene expressions of hPDLFs and hPDLSCs were observed for interleukin (IL)-$1{\beta}$, IL-6, tumor necrosis factor (TNF)-${\alpha}$, osteoprotegerin (OPG), receptor activator of nuclear factor kappa-B ligand (RANKL), and RANKL/OPG using real-time polymerase chain reaction (PCR) at 0, 6, 24, and 48 hours after treatment. The experiments were performed with the following groups for hPDLFs and hPDLSCs; 1) No treat, 2) EGCG alone, 3) P. gingivalis LPS alone, 4) EGCG+P. gingivalis LPS. Results: The 20 ${\mu}M$ of EGCG and 20 ${\mu}g/mL$ of P. gingivalis LPS had the lowest cytotoxic effects, so those concentrations were used for further experiments. The proliferations of hPDLFs and hPDLSCs increased in all groups, though the 'EGCG alone' showed less increase. In real-time PCR, the hPDLFs and hPDLSCs of 'EGCG alone' showed similar gene expressions to those cells of 'no treat'. The gene expressions of 'P. gingivalis LPS alone' in both hPDLFs and hPDLSCs were highly increased at 6 hours for IL-$1{\beta}$, IL-6, TNF-${\alpha}$, RANKL, and RANKL/OPG, except the RANKL/OPG in hPDLSCs. However, those increased gene expressions were down-regulated in 'EGCG+P. gingivalis LPS' by the additional treatment of EGCG. Conclusions: Our results demonstrate that EGCG could exert an anti-inflammatory effect in hPDLFs and hPDLSCs against a major pathogen of periodontitis, P. gingivalis LPS.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.34 no.4
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• pp.419-427
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• 2008

The present study aimed to investigate the osteogenic potentials of differentiated osteoblast-like cells (DOCs) induced from bone marrow-derived mesenchymal stem cells (MSCs) on ${\beta}-tricalcium$ phosphate (${\beta}-TCP$) with recombinant human bone morphogenetic protein (rhBMP-2) in vitro. Osteoblast differentiation was induced in confluent cultures by adding 100 nM dexamethasone, 10 mM ${\beta}$-glycerophosphate, 50 mM L-ascorbic acid. The Alizarin red S staining and reverse transcriptase-polymerase chain reaction (RT-PCR) were perfomed to examine the mRNA expression of alkaline phosphatase (ALP), bone sialoprotein (BSP), osteocalcin (OCN), receptor activator for nuclear factor ${\kappa}B$ ligand (RANKL), runt-related transcription factor 2 (RUNX2), collagen-Ⅰ (COL-Ⅰ). There were no significant differences in the osteogenic potentials of DOCs induced from MSCs on ${\beta}-TCP(+/-)$. According to the incubation period, there were significant increasing of Alizadin red S staining in the induction 3 weeks. The mRNA expression of ALP, RUNX2, and RANKL were higher in DOCs/${\beta}-TCP(-)$ than DOCs/${\beta}-TCP(+)$. According to rhBMP-2 concentrations, the mRNA expression of BSP was significantly increased in DOCs/${\beta}-TCP(+)$ compared to that of DOCs/${\beta}-TCP(-)$ on rhBMP 10 ng/ml. Our study presented the ${\beta}-TCP$ will have the possibility that calcium phosphate directly affect the osteoblastic differentiation of the bone marrowderived MSCs.

• Animal Bioscience
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• v.34 no.7
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• pp.1169-1180
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• 2021

Objective: This research aimed to study the effects of Artemisia argyi flavonoids (AAF) supplemented in diets on the growth performance and immune function of broiler chickens challenged with lipopolysaccharide (LPS). Methods: A total of one hundred and ninety-two 1-d-old broiler chicks were assigned into 4 treatment groups, which were, respectively, fed a basal diet (control), fed a diet with 750 mg/kg AAF, fed a basal diet, and challenged with LPS, fed a diet with 750 mg/kg AAF, and challenged with LPS. Each treatment had six pens with 8 chicks per pen. On days 14, 16, 18, 20 (stress phase I) and 28, 30, 32, 34 (stress phase II), broilers were injected with LPS (500 ㎍/kg body weight) or an equivalent amount of saline. Results: The results demonstrated that dietary AAF significantly improved the body weight (d 21) and alleviated the decrease of average daily gain in broilers challenged with LPS on d 21 and d 35 (p<0.05). Dietary AAF increased bursa fabricius index, and dramatically attenuated the elevation of spleen index caused by LPS on d 35 (p<0.05). Furthermore, serum interleukin-6 (IL-6) concentration decreased with AAF supplementation on d 21 (p<0.05). Diet treatment and LPS challenge exhibited a significant interaction for the concentration of IL-1β (d 21) and IL-6 (d 35) in serum (p<0.05). Additionally, AAF supplementation mitigated the increase of IL-1β, IL-6 in liver and spleen induced by LPS on d 21 and 35 (p<0.05). This study also showed that AAF supplementation significantly reduced the expression of IL-1β (d 21) and nuclear transcription factor kappa-B p65 (d 21 and 35) in liver (p<0.05), and dietary AAF and LPS treatment exhibited significant interaction for the gene expression of IL-6 (d 21), toll like receptor 4 (d 35) and myeloid differentiation factor 88 (d 35) in spleen (p<0.05). Conclusion: In conclusion, AAF could be used as a potential natural immunomodulator to improve growth performance and alleviate immune stress in broilers challenged with LPS.

• Journal of Korean Medicine Rehabilitation
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• v.32 no.4
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• pp.9-18
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• 2022

Objectives This study was conducted to confirm the anti-inflammatory effect of Naetakbaekryeom-san (NTB), and whether it could be another treatment for inflammatory diseases. Methods The NTB water extract was extracted with hot water at 100℃ for 2 hours, concentrated at 80℃ under reduced pressure, and used. After 2 hours of pretreatment with NTB and positive control Bay11-7082, nitric oxide (NO), inducible NO synthase (iNOS), interleukin (IL)-6, IL-1𝛽, tumor necrosis factor alpha (TNF-𝛼) were measured in RAW264.7 cells activated with lipopolysaccharides (LPS) 500 ng/mL. After 2 hours of pretreatment with NTB, the anti-inflammatory effect of NTB was evaluated by measuring nuclear factor kappa-light-chain-enhancer of activated B cells (NF-𝜅B) in RAW264.7 cells and 293T cells activated with phorbol 12-myristate 13-acetic acid (PMA) 30 ng/mL. Results In RAW264.7 cells activated with LPS, NTB at concentrations of 0.1, 0.3, and 1.0 mg/mL showed no cytotoxicity, significantly inhibited NO production and inhibition of iNOS expression. TNF-𝛼 cytokine levels was not regulated, but NTB at each concentration inhibited the production of IL-1𝛽 and IL-6, and the effect was higher than that of the positive control Bay11-7082 (20 𝜇M). In PMA-activated RAW264.7 cells and 293T cells, each concentration of NBT decreased the NF-𝜅B transcriptional activity, with the greatest decrease at 1 mg/mL. Conclusions These results demonstrated the anti-inflammatory effect of NTB water extracts, but further studies such as comparison of anti-inflammatory effects and antioxidant effects by NTB component, comparison of effects according to extraction solvents, and clinical studies are needed.

• Nutrition Research and Practice
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• v.18 no.5
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• pp.633-646
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• 2024

BACKGROUND/OBJECTIVES: Cladophora glomerata extract (CGE), rich in polyphenols, was reported to exhibit antidiabetic and renoprotective effects by modulating the functions of protein kinases-mediated organic anion transporter 1 (Oat1) and 3 (Oat3) in rats with type 2 diabetes mellitus (T2DM). Nevertheless, the antioxidant effects of CGE on such renoprotection have not been investigated. This study examined the mechanisms involved in the antioxidant effects of CGE on renal organic anion transport function in an in vivo study. MATERIALS/METHODS: Diabetes was induced in the rats through a high-fat diet combined with a single dose of 40 mg/kg body weight (BW) streptozotocin. Subsequently, normal-diet rats were supplemented with a vehicle or 1,000 mg/kg BW of CGE, while T2DM rats were supplemented with a vehicle, CGE, or 200 mg/kg BW of vitamin C for 12 weeks. The study evaluated the general characteristics of T2DM and renal oxidative stress markers. The renal organic transport function was assessed by measuring the para-aminohippurate (PAH) uptake using renal cortical slices and renal inflammatory cytokine expression in the normal diet (ND) and ND + CGE treated groups. RESULTS: CGE supplementation significantly reduced hyperglycemia, hypertriglyceridemia, insulin resistance, and renal lipid peroxidation in T2DM rats. This was accompanied by the normalization of high expressions of renal glutathione peroxidase and nuclear factor kappa B by CGE and vitamin C. The renal anti-inflammation of CGE was evidenced by the reduction of tumor necrosis factor-1α and interleukin-1β. CGE directly blunted sodium nitroprusside-induced renal oxidative/nitrosative stresses and mediated the PAH uptake in the normally treated CGE in rats was particularly noteworthy. These data also correlated with reduced nitric oxide production, highlighting the potential of CGE as a therapeutic agent for managing T2DM-related renal complications. CONCLUSION: These findings suggest that CGE has antidiabetic effects and directly prevents diabetic nephropathy through oxidative/nitrosative stress pathways.

• Journal of Ginseng Research
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• v.46 no.5
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• pp.628-635
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• 2022

Background: Ulcerative colitis (UC) is the large intestine disease that results in chronic inflammation and ulcers in the colon. Rg3-enriched Korean Red Ginseng extract (Rg3-RGE) is known for its pharmacological activities. Persicaria tinctoria (PT) is also used in the treatment of various inflammatory diseases. The aim of this study is to investigate the attenuating effects of Rg3-RGE with PT on oxazolone (OXA)-induced UC in mice. Methods: A total of six groups of mice including control group, OXA (as model group, 1.5%) group, sulfasalazine (75 mg/kg) group, Rg3-RGE (20 mg/kg) group, PT (300 mg/kg) group, and Rg3-RGE (10 mg/kg) with PT (150 mg/kg) group. Data on the colon length, body weight, disease activity index (DAI), histological changes, nitric oxide (NO) assay, Real-time PCR of inflammatory factors, ELISA of inflammatory factors, Western blot, and flow cytometry analysis were obtained. Results: Overall, the combination treatment of Rg3-RGE and PT significantly improved the colon length and body weight and decreased the DAI in mice compared with the treatment with OXA. Additionally, the histological injury was also reduced by the combination treatment. Moreover, the NO production level and inflammatory mediators and cytokines were significantly downregulated in the Rg3-RGE with the PT group compared with the model group. Also, NLR family pyrin domain containing 3 (NLRP3) inflammasome and nuclear factor kappa B (NF-𝛋B) were suppressed in the combination treatment group compared with the OXA group. Furthermore, the number of immune cell subtypes of CD4⁺ T-helper cells, CD19⁺ B-cells, and CD4⁺ and CD25⁺ regulatory T-cells (Tregs) was improved in the Rg3-RGE with the PT group compared with the OXA group. Conclusion: Overall, the mixture of Rg3-RGE and PT is an effective therapeutic treatment for UC.

• The Korea Journal of Herbology
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• v.32 no.5
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• pp.1-6
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• 2017

Objectives : Corni Fructus (CF) is traditional herbal medicine used on polyuria, low back pain, and tinnitus. This study aimed to evaluate inhibits skin wrinkle formation effect of CF. Methods : To evaluate the produce inhibition effect of CF, SD-rats were distributed into four groups; normal rats (Nor), AGEs (advenced glycation end product)-induced rats (Con), AGEs-induced rats treated with 100mg/kg CF (CF). To induce AGEs, streptozotocin (50mg/kg) was administered intraperitoneally and after 3 days oral administrated 100mM methyl glyoxal for 3 weeks. Results : The oral administration of CF suppressed the reactive oxygen specis (ROS) in serum. The AGEs in skin tissues was significantly reduced through treatment of CF. Furthermore, the expressions of AGEs related proteins such as polyclonal anti-$N^e$-(carboxymethyl)lysine (CML), anti-$N^e$-(carboxyethyl)lysine (CEL), AGE receptors (RAGE) were decreased in CF treated group compared with the control group in skin tissues. Inflammation-related proteins such as Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6) reduced in CF treatment group than control group. AGE-induced rats exhibited that the significant decreased collagen however, CF treatment (100mg/kg of body weight) up regulated collagen by improved the expression levels of skin fibril-related genes such as Matrix metalloproteinase (MMP-1). Conclusion : Taken together, our study suggests that CF regulates ROS to prevent accumulation of AGEs and inhibits skin wrinkles. Our finding indicate that CF may be an effective agent for inhibits AGEs formation, and improved skin wrinkle.

• Journal of Life Science
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• v.25 no.9
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• pp.993-999
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• 2015

The beetle Popillia flavosellata has been no reported its functional effects. In this study, we investigated the anti-inflammatory effect of P. flavosellata ethanol extract (PFE) on RAW 264.7 mouse macrophage cells treated with lipopolysaccharide (LPS) for the induction of inflammation. First, we examined the cytotoxicity of PFE in the RAW 264.7 cells at a concentration of 2,000 μg/ml or less. To evaluate the anti-inflammatory effects of PFE, we investigated the expression levels of proinflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-6, and proinflammatory enzymes, such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-induced RAW 264.7 cells. In addition, we examined whether PFE inhibited the translocation of nuclear factor kappa B (NF-κB) p65 into the nucleus in the LPS-induced RAW 264.7 cells. We found that the protein levels of TNF-α and IL-6 were decreased in the LPS-induced RAW 264.7 cells after the treatment with PFE in a dose-dependent manner. In addition, we confirmed that PFE inhibited the translocation of NF-κB p65 into the nucleus, as well as the protein expression levels of iNOS and COX-2. Accordingly, we propose that PFE exerts an anti-inflammatory effect through the down-regulation of NF-κB p65, TNF-α, IL-6, iNOS, and COX-2 via the toll like receptor (TLR)-4 inflammatory signaling pathway.