• 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.

• Proceedings of the SCSK Conference
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• 2003.09a
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• pp.780-803
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• 2003

Exposure of skin cells, particularly keratinocytes to various nuclear factor-kappaB ($\textrm{NF}_{-{\kappa}}\textrm{B}$) activators [e.g. tumor necrosis factor-$\alpha$, interleukin-1, lipopolysaccharides, and ultraviolet light] leads to phosphorylation and degradation of the inhibitory protein, $\textrm{I}_{{\kappa}}\textrm{B}$. Liberated $\textrm{NF}_{-{\kappa}}\textrm{B}$ is translocated into the nucleus where it can change or alter expression of target genes, resulting in the secretion of extracellular signaling molecules including melanotrophic factors affecting melanocyte. In order to demonstrate the possible role of $\textrm{NF}_{-{\kappa}}\textrm{B}$ activation on the synthesis of melanotrophic factors from the keratinocytes, the activities of $\textrm{NF}_{-{\kappa}}\textrm{B}$ induced by melanogenic inhibitors (MIs) were determined in human HaCaT keratinocytes transfected with $\textrm{pNF}_{-{\kappa}}\textrm{B}$-SEAP-NPT plasmid. Transfectant cells released the secretory alkaline phosphatase (SEAP) as a transcription reporter in response to the $\textrm{NF}_{-{\kappa}}\textrm{B}$ activity and contain the neomycin phosphotransferase (NPT) gene for the dominant selection marker for geneticin resistance. MIs such as niacinamide, kojic acid, hydroquinone, resorcinol, arbutin, and glycolic acid were preincubated with transfectant HaCaT cells for 3 h and then ultraviolet B (UVB) was irradiated. $\textrm{NF}_{-{\kappa}}\textrm{B}$ activation was measured with the SEAP reporter gene assay using a fluorescence detection method. Of the Mis tested, kojic acid ($IC_{50}$/ = 60 $\mu$M) was found to be the most potent inhibitor of UVB-upregulating $\textrm{NF}_{-{\kappa}}\textrm{B}$ activation in transfectant HaCaT cells, which is followed by niacinamide ($IC_{50}$/= 540 $\mu$M). Pretreatment of the transfectant HaCaT cells with the Mis, especially kojic acid and niacinamide, effectively lowered $\textrm{NF}_{-{\kappa}}\textrm{B}$ binding measured by electrophoretic mobility shift assay. Furthermore, these two inhibitors remarkably reduced the secretion level of IL-6, one of melanotrophic factors, triggered by UV-radiation of the HaCaT cells. These observations suggest that Mis working at the in vivo level might act partially through the modulation of the synthesis of melanotrophic factors in keratinocyte.

• The Korea Journal of Herbology
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• v.30 no.4
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• pp.81-88
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• 2015

Objectives : The aim of present study was to evaluate the beneficial effect of Scutellariae Radix (SR) and Scutellariae Radix EtOH-heated at 200℃ (SR200) using lipopolysaccharide (LPS) treated intestine of mice.Methods : Extract of SR and SR200 were orally administrated. Their effects were compared with vehicletreated LPS and normal groups. Subsequently, we measured reactive oxygen species (ROS) and nitric oxide in the serum and western blotting in the intestine.Results : The average weight in LPS treated (Vehicle) group was lowered significantly compare to that in non-treated normal group and this weight loss in the vehicle group was effectively prevented by the administration of SR and SR200 respectively. The increased oxidative stress biomarker levels such as reactive oxygen species (ROS) and nitric oxide (NO) in the serum was markedly decreased by treated with SR200. The decreased levels of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) induced by LPS injection were significantly restored by both SR and SR200 treatment. Moreover, increased inflammatory mediators and cytokines such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in the LPS treated vehicle mice were significantly decreased through down-regulation c-JUN through reduction of oxidative stress.Conclusions : SR and SR200 could have benefit effect through down-regulation of abnormal oxidative stress in LPS induced intestine injury mice. Moreover, The anti-inflammatory activity of SR200 extract was better than SR extract in the LPS induced intestine injury mice.

• Korean Journal of Clinical Laboratory Science
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• v.52 no.3
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• pp.253-260
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• 2020

Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disease that can be described by the occurrence of dementia due to a decline in cognitive function. The disease is characterized by the formation of extracellular and intracellular amyloid plaques. Amyloid beta (Aβ) is a hallmark of AD, and microglia can be activated in the presence of Aβ. Activated microglia secrete pro-inflammatory cytokines. Furthermore, S100A9 is an important innate immunity pro-inflammatory contributor in inflammation and a potential contributor to AD. This study examined the effects of metformin and α-LA on the inflammatory response and NLRP3 inflammasome activation in Aβ- and S100A9-induced BV-2 microglial cells. Metformin and α-LA attenuated inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). In addition, metformin and α-LA inhibited the phosphorylation of JNK, ERK, and p38. They activated the nuclear factor kappa B (NF-κB) pathway and the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome. Moreover, metformin and α-LA reduced the marker levels of the M1 phenotype, ICAM1, whereas the M2 phenotype, ARG1, was increased. These findings suggest that metformin and α-LA are therapeutic agents against the Aβ- and S100A9-induced neuroinflammatory responses.

• Asian-Australasian Journal of Animal Sciences
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• v.33 no.9
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• pp.1507-1519
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• 2020

Objective: The current research was aimed to profile the transcriptomic picture of the peripheral blood lymphocytes (PBLs) associated with immunity in Chinese Holsteins supplemented orally with coated folic acid during the periparturient period. Methods: The total of 123 perinatal cows were selected for this study and divided into three groups; group A (n = 41, 240 mg/500 kg cow/d), group B (n = 40, 120 mg/500 kg cow/d) and group C (n = 42, 0 mg/cow/d) based on the quantity of folic acid fed. Three samples of PBLs were selected from each folic acid treated group (high, low, and control) and RNA sequencing method was carried out for transcriptomic analysis. Results: The analysis revealed that a higher number of genes and pathways were regulated in response to high and low folic acid supplementation compared to the controls. We reported the novel pathways tumor necrosis factor (TNF) signaling, antigen processing and presentation, Staphylococcus aureus infection and nuclear factor (NF)-kappa B signaling pathways) and the key genes (e.g. C-X-C motif chemokine ligand 10, TNF receptor superfamily member 1A, cluster difference 4, major histocompatibility complex, class II, DQ beta, NF-kappa-B inhibitor alpha, and TNF superfamily 13) having great importance in immunity and anti-inflammation in the periparturient cows in response to coated folic acid treatment. Conclusion: Collectively, our study profiled first-time transcriptomic analysis of bovine lymphocytes and compared the involved cytokines, genes, and pathways between high vs control and low vs control. Our data suggest that the low folic acid supplementation (120 mg/500 kg) could be a good choice to boost appropriate immunity and anti-inflammation as well as might being applied to the health improvement of perinatal dairy cows.

• Journal of Acupuncture Research
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• v.32 no.3
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• pp.1-13
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• 2015

Purpose : This research was conducted to investigate the effect of sweet bee venom pharmacopuncture and low level laser acupuncture on paw edema, pain index, anti-inflammatory factor, AST, ALT and complete blood cell count of a rat model with Complete Freund's Adjuvant-induced arthritis. Methods : Five experimental groups were formed with each consisting of six rats: normal group, control group, sweet bee venom pharmacopuncture group, lower level laser acupuncture group, and sweet bee venom pharmacopuncture, lower level laser acupuncture group. The experimental model of arthritis was induced by two injections of Freund's adjuvant into the left knee joint of Sprague Dawley(SD) rats. The second injection of Freund's adjuvant was given ten days after the first one. Ten days later, sweet bee venom pharmacopuncture and low level laser acupuncture were administered separately or together by assigned groups at $GB_{34}$ and $GB_{39}$ of rats twice a week for a total of six times. Thereafter, edema rate, pain index, tumor necrosis factor-${\alpha}$, interleukin-6, aspartate aminortansferase, alanine aminotransferase and complete blood cell count were measured. Results : We noticed synergic effects of sweet bee venom pharmacopuncture and low level laser acupuncture according to the results of the paw edema and Von Frey pain index. The sweet bee venom pharmacopuncture(BVA) and sweet bee venom pharmacopuncture+ low level laser acupuncture(BVA+LLA) groups experienced a more significant effect when compared with the control group. Conclusions : These results suggest that Sweet Bee Venom Pharmacopuncture and low level laser acupuncture at GB34 and GB39 have a significant anti-inflammatory effect on Freund's adjuvant arthritis in rats.

• The Journal of Internal Korean Medicine
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• v.23 no.1
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• pp.15-23
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• 2002

Objective : We aimed to identify the dose-dependent inhibitory effects of Sabaek-san(瀉白散) and Sabaeksan plus Sasam(Adenophorae Radix) 瀉白散加沙蔘) on the mRNA expressions of Interleukin(IL)-6, IL-8 and granulocyte macrophage colony stimulating factor(GM-CSF) involved in the asthma model. Materials and Methods : Through this study, BEAS-2B cell lines, human epithelial cells were used. These cells were stimulated by tumor necrosis factor(TNF)-${\alpha}$, IL-1${\beta}$ and histamine for artificial inflammatory expression. ${\beta}$-action messenger RNA(mRNA) was used for standards. After each 24hours of Sabaeksan and Sabaeksan plus Sasam treatment, total cellular RNAs were collected by treating RNA zol directly on living cells, Then the transcriptional activities of IL-6, 8 and GM-CSF were measured by RT-PCR with electrophoresis, Results : The mRNA expressions of IL-6 are significantly inhibited compared to those of controlled group at 40 and 100ug/ml of Sabaeksan extract and $100{\mu}g/ml$ of Sabaeksan plus Sasam extract (p<0.05). The mRNA expressions of IL-8 are significantly inhibited compared to that of controlled group at 2.40 and 100 ug/ml of Sabaeksan extract and $40.100{\mu}g/ml$ of Sabaeksan plus Sasam extract(p<0.05) THe mRNA expressions of GM-CSF are significantly inhibited compared to those of the controlled group at $100{\mu}g/ml$ of Sabaeksan extract adn $40.100{\mu}g/ml$ of Sabaeksan plus Sasam extract.(p<0.05) Conclusions : This study shows that Sabaeksan and Sabaeksan plus Sasam have dose-dependent inhibitory effects on the mRNA expressions of IL-6, IL-8 and GM-CSF in human epithelial cells. Therefore, these types of herb medicine may inhibit the inflammatory process of asthma. Advanced studies are required to investigate the mechanisms of inhibition by herb medicine in the asthma model.

• Journal of Applied Biological Chemistry
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• v.60 no.3
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• pp.191-198
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• 2017

Hyaluronidase inhibitory activity as inflammatory factor of Koreinsis chinensis leaf ethanol extract was showed higher inhibitory activity than water extract. 29.5% inhibitory activity was shown at concentration of $200{\mu}g/mL$ phenolics. Lipopolysaccharide (LPS)-stimulated Raw 264.7 cells were treated with different concentrations ($5-25{\mu}g/mL$) of Koreinsis chinensis leaf extract and the amount of nitric oxide (NO) was determined; LPS-treated cells produced 3 times more NO than non-LPS treated cells. Moreover, the NO production in cells treated with Koreinsis chinensis leaf extract showed inhibitory effect in a concentration-dependent manner. Due to the stimulant-induced NO production is regulated by the inducible nitric oxide synthase (iNOS), we determined the iNOS protein level to elucidate the mechanism by which the NO production was inhibited. It was reduced by 40% with a Koreinsis chinensis leaf extract concentration of $25{\mu}g/mL$ and identified iNOS inhibition in dose-dependent manner. The prostaglandin $E_2$ production in cells treated with Koreinsis chinensis leaf extract was reduced by 26.2% at concentration of $25{\mu}g/mL$. The protein expression of cyclooxygenase-2 in LPS-treated Raw 264.7 cells was inhibited by 64% at $25{\mu}g/mL$ of Koreinsis chinensis leaf extract. Koreinsis chinensis leaf extract had a concentration-dependent inhibitory effect on the production of tumor necrosis factor-${\alpha}$ and interleukin-6 as pro-inflammatory cytokine in LPS-treated Raw 264.7 cells at $25{\mu}g/mL$ of Koreinsis chinensis leaf extract. Their levels were decreased by 61.7 and 62% respectively.

• Journal of Korean Medicine Rehabilitation
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• v.19 no.2
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• pp.27-49
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• 2009

Objectives : The purpose of this study was to investigate the effects of Yanghyuljanggeungunbo-tang(Yangxuezhuangjinjianbu-tang) and Cervi Cornu Parvum pharmaco-acupuncture in Spinal Cord Injury(SCI)-induced rats. Methods : The subjects were divided into 5 groups ; Normal, Control no treatment after SCI, Experimental I taken with Yanghyuljanggeungunbo-tang (Yangxuezhuangjinjianbu-tang) 500 mg/kg $0.5m{\ell}$ daily after inducing SCI. Experimental II taken with Cervi Cornu Parvum pharmaco-acupuncture at Taegye(KI3) and $Yangnungch{\acute{o}}n$(GB34) after inducing SCI and Experimental III taken with Yanghyuljanggeungunbo-tang(Yangxuezhuangjinjianbu-tang) 500 mg/kg $0.5m{\ell}$ and Cervi Cornu Parvum pharmaco-acupuncture at KI3 and GB34 to SCI-induced rats. After each operation, the present author observed the motor behavior recovery and nerve regeneration by analysis of the motor behavior tests, EMG, hematological(AST, ALT, WBC), histological and immunological changes. Rats were tested at modified Tarlov test at the 1st, 2nd, 3rd, 4th day, and Motor behavior test at 1st, 3rd, 7th, 14th, 21st day. Results : Results are as follows. 1. All the experimental groups were improved compared with control group in the motor behavior tests including Tarlov test, Basso-Beattle-Bresnahan locomotor rating scale, modified inclined plane test, open field test, grid walk test and narrow beam test. Especially Experimental III was improved significantly among other groups. 2. In EMG test, H wave appeared weak only in Experimental III. And M wave was increased significantly in Experimental III. 3. All the experimental groups were significantly decreased compared with control group in serum AST, serum ALT and serum WBC tests. 4. significantly decreased in Tumor Necrosis Factor-${\alpha}$ test compared with the first day of SCI. 5. Muscle contraction and denaturation of all the experimental groups were inhibited in histological observations of gastrocnemius muscle. Especially, those of experimental III was more effective. 6. NGF and BDNF of spinal cord gray matter in all the experimental groups were increased compared with control group. Especially, those of experimental III was more effective. Conclusions : As above, it can be suggested that Yanghyuljanggeungunbo-tang(Yangxuezhuangjinjianbu-tang) and Cervi Cornu Parvum pharmaco-acupuncture may improve motor behavior, EMG, hematological, histological and immunological findings in Spinal Cord Injury(SCI)-induced rats. Especially, effects will be somewhat better in combination of these two treatments.

• Korean Journal of Veterinary Research
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• v.60 no.1
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• pp.25-32
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• 2020

Natural killer (NK) cells play have a crucial role in the early phase of immune responses against various pathogens. We compared characteristics of canine NK cells against two canine mammary carcinoma cell lines, REM134 and CF41.Mg. REM134 showed higher expression of progesterone receptor, proliferative cell nuclear antigen, Ki67, multiple drug resistance, Bmi-1, c-myc, E-cadherin, and human epidermal growth factor receptor type-2 than that of CF41.Mg. For specific expansion and activation of NK cells, we isolated CD5 negative cells from canine peripheral blood mononuclear cells and co-cultured K562 cells in the presence of interleukin (IL)-2, IL-15, and IL-21 for 21 days. As a result, we found that expression markers of activated NK cells such as NKp30, NKp44, NKp46, NKG2D, CD244, perforin, granzyme B, and tumor necrosis factor alpha were highly upregulated. In addition, we found there was upregulated production of interferon gamma of activated NK cells against target cells such as REM134 and CF41.Mg. Specifically, we observed that cytotoxicity of NK cells against target cells was more sensitively reacted to CF41.Mg than REM134. Based on the results of this study, we recommend the development of an experimental application of CF41Mg, which has not been reported in canine mammary carcinoma research.