• Molecules and Cells
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• v.46 no.10
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• pp.627-636
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• 2023

Periodontal disease is a chronic inflammatory disease that leads to the gradual destruction of the supporting structures of the teeth including gums, periodontal ligaments, alveolar bone, and root cementum. Recently, interests in alleviating symptoms of periodontitis (PD) using natural compounds is increasing. Avenanthramide-C (Avn-C) is a polyphenol found only in oats. It is known to exhibit various biological properties. To date, the effect of Avn-C on PD pathogenesis has not been confirmed. Therefore, this study aimed to verify the protective effects of Avn-C on periodontal inflammation and subsequent alveolar bone erosion in vitro and in vivo. Upregulated expression of catabolic factors, such as matrix metalloproteinase 1 (MMP1), MMP3, interleukin (IL)-6, IL-8, and COX2 induced by lipopolysaccharide and proinflammatory cytokines, IL-1β, and tumor necrosis factor α (TNF-α), was dramatically decreased by Avn-C treatment in human gingival fibroblasts and periodontal ligament cells. Moreover, alveolar bone erosion in the ligature-induced PD mouse model was ameliorated by intra-gingival injection of Avn-C. Molecular mechanism studies revealed that the inhibitory effects of Avn-C on the upregulation of catabolic factors were mediated via ERK (extracellular signal-regulated kinase) and NF-κB pathway that was activated by IL-1β or p38 MAPK and JNK signaling that was activated by TNF-α, respectively. Based on this study, we recommend that Avn-C may be a new natural compound that can be applied to PD treatment.

• Journal of The Korean Society of Integrative Medicine
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• v.7 no.4
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• pp.61-69
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• 2019

Purpose : Human gingival fibroblast cell is one of the the main cell types in periodontal tissue, which they can show anti-inflammatory activity through the production of numerous lines of inflammatory mediators such as inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and interleukins. Porphyromonas gingivalis, one of the oral pathogens, has reported to play a critical role in the development of periodontal diseases. This study aimed to investigate anti-inflammatory and antioxidative activities of Gracilaria textorii ethanol extract (GTEE) in P. gingivalis derived lipopolysaccharide (LPS-PG) stimulated human gingival fibroblast (HGF)-1 cell line. Methods : In order to analyze anti-inflammatory and antioxidative activities of GTEE in HGF-1 cell line, NOS enzyme activity, expression levels of iNOS, COX-2, NAD(P)H quinone dehydrogenase (NQO)1 and their transcription factors were estimated by Griess reaction and western hybridization. Results : LPS-PG induced overexpression of iNOS and COX-2, which was significantly attenuated by GTEE treatment in a dose-dependent manner without any cytotoxicity. In addition, intracellular NOS activity was in accordance with the result of iNOS expression. Due to important role in the regulation of inflammatory responses, phosphorylated status of p65 and c-jun, each subunit of nuclear factor (NF)-κB and activator protein (AP)-1, was also dose-dependently ameliorated by GTEE treatment. One of phase II enzymes, NQO1, and its transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2), were analyzed since elevated phase II enzyme expression inhibited inflammatory response, which was significantly elevated by GTEE treatment in HGF-1 cell line. Conclusion : In conclusion, GTEE mitigated LPS-PG-stimulated inflammatory responses by attenuating NF-κB and AP-1 activation as well as accelerating NQO1 and Nrf2 expression in HGF-1 cell line. These results indicate that GTEE might be utilized a promising strategy for potential anti-inflammatory agent in periodontal diseases.

• Natural Product Sciences
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• v.15 no.2
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• pp.83-89
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• 2009

Polygoni multiflori Ramulus (PM), the stem of Polygonum multiflorum Thunb. has been widely used as a traditional medicine for the treatment of lots of diseases. In macrophages, nitric oxide is released as an inflammatory mediator and has been proposed to be an important modulator of many pathophysiological conditions in inflammation. In the present study, it was investigated that the inhibitory effects on NO and proinflammatory cytokines such as tumor necrosis factor alpha (TNF-${\alpha}$), interleukin-6 (IL-6) and the mechanism of down-regulation of immune response by 85% methanol extracts of PM in mouse (C57BL/6) peritoneal macrophages. Extracts of PM (0.1, 1 mg/ml) suppressed NO production and showed inhibition of proinflammatory cytokines like TNF-${\alpha}$, IL-6 and it attenuated iNOS and COX-2 expression via down-regulation of NF-${\kappa}$B activation. The present results indicate that the 85% methanol extracts of PM has an inhibitory effect on the production of NO through down-regulation of iNOS expression in LPS stimulated mouse peritoneal macrophages and therefore may be beneficial in diseases which related to macrophage-mediated inflammatory disorders.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.5
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• pp.1202-1209
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• 2008

Peroxynitrite ($ONOO^-$), superoxide anion radical (${\cdot}\;{O_2}^-$) and nitric oxide (NO) are cytotoxic because they can oxidize several cellular components such as proteins, lipids and DNA. They have been implicated in the aging processes, and age-related diseases such as Alzheimer's disease, rheumatoid arthritis, cancer, diabetes, obesity and atherosclerosis. The aim of this study was to investigate the effects of Ojunghwan on the generation of peroxynitrite ($ONOO^-$), nitric oxide (NO) and superoxide anion radical (${\cdot}\;{O_2}^-$), and on the expression of $NF-{\kappa}B$-dependent inflammatory proteins in ob/ob mice. Mice were grouped and treated for 5 weeks as follows. Both the normal lean (C57/BL6J black mice) and control obese (ob/ob mice) groups have received the standard chow. The experimental groups were fed with a diet of chow supplemented with 30 and 90 mg Ojung-hwan per 1 kg of body weight for 14 days. For this study, the fluorescent probes, namely 2',7'-dichlorodihydrofluorescein diacetate (DCFDA), 4,5-diaminofluorescein (DAF-2) and dihydrorhodamine 123 (DHR 123) were used. Western blot was performed using anti-phospho $I{\kappa}B-{\alpha}$, $anti-IKK-{\alpha}$, $anti-NF-{\kappa}B$ (p50, p65), anti-COX-2, anti-iNOS, anti-VCAM-1 and anti-MMP-9 antibodies, respectively. Ojunghwan inhibited the generation of $ONOO^-$, NO and ${\cdot}\;{O_2}^-$ in the lipopolysaccharide (LPS)-treated mouse kidney postmitochondrial fraction in vitro. The generation of $ONOO^-$, NO, ${\cdot}\;{O_2}^-$ and $PGE_2$ were inhibited in the Ojunghwan-administered ob/ob mice groups. The GSH/GSSG ratio was decreased in the ob/ob mice, whereas that were improved in the Ojunghwan-administered groups. Ojunghwan inhibited the expression of $phospho-I{\kappa}B-{\alpha}$, $IKK-{\alpha}$, $NF-{\kappa}B$ (p50, p65), COX-2, iNOS, VCAM-1 and MMP-9 genes. These results suggest that Ojunghwan is an effective scavenger of $ONOO^-$, ${\cdot}\;{O_2}^-$, NO and $PGE_2$, and has an inhibitory effect on the expression of $NF-{\kappa}B$-dependent inflammatory genes in ob/ob mice. Therefore, Ojunghwan might be used as a potential therapeutic drug against the inflammation process and inflammation- related diseases.

• The Journal of Korean Medicine
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• v.30 no.1
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• pp.51-63
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• 2009

Objectives: Peroxynitrite ($ONOO^-$), superoxide anion radical (${\cdot}{O_2}^-$ and nitric oxide (NO) are cytotoxic because they can oxidize several cellular components such as proteins, lipids and DNA. They have been implicated in the aging processes, and age-related diseases such as Alzheimer's disease, rheumatoid arthritis, cancer, diabetes, obesity and atherosclerosis. The aim of this study was to investigate the $ONOO^-$, NO, ${\cdot}{O_2}^-$ scavenging and NF-${\kappa}B$ related anti-inflammatory activities of Sotosaja-hwan in ob/ob mice. Methods: Mice were grouped and treated for 5 weeks as follows. Both the normal lean (C57/BL6J black mice) and control obese (ob/ob mice) groups have received standard chow. The experimental groups were fed with a diet of chow supplemented with 30 and 90 mg Sotosaja-hwan per 1 kg of body weight for 14 days. For this study, the fluorescent probes, namely 2',7'-dichlorodihydrofluorescein diacetate (DCFDA), 4,5-diaminofluorescein (DAF-2) and dihydrorhodamine 123 (DHR 123) were used. Western blotting was performed using anti-phospho-$I{\kappa}B$-${\alpha}$, anti-IKK-${\alpha}$, anti-NF-${\kappa}B$ (p50, p65), anti-COX-2, anti-iNOS, anti-YCAM-1 and anti-MMP-9 antibodies, respectively. Results: Sotosaja-hwan inhibited the generation of $ONOO^-$, NO and ${\cdot}{O_2}^-$ in the lipopolysaccharide (LPS)-treated mouse kidney postmitochondrial fraction in vitro. The generation of $ONOO^-$, NO, ${\cdot}{O_2}^-$ and PGE2 were inhibited in the Sotosaja-hwan-administered ob/ob mice groups. The GSH/GSSG ratio was decreased in the ob/ob mice, whereas the ratio was improved in the Sotosaja-hwan-administered groups. Sotosaja-hwan inhibited the protein expression levels of phospho-$I{\kappa}B$-${\alpha}$, IKK-${\alpha}$, NF-${\kappa}B$ (p50, p65), COX-2, iNOS, YCAM-1 and MMP-9 genes. Conclusions: These results suggest that Sotosaja-hwan is an effective $ONOO^-$, ${\cdot}{O_2}^-$ and NO scavenger and has NF-kB related anti-inflammatory activity in ob/ob mice. Therefore, Sotosaja-hwan might be a potential therapeutic drug against the inflammation process and inflammation-related diseases.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.48 no.4
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• pp.303-312
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• 2022

In this study, Cyperus rotundus (C. rotundus) was fractionated into ethyl acetate to identify α-cyperone, a representative indicator, and its ethyl acetate fraction were evaluated to confirm the possibilityas a functional cosmetic ingredient. As a result of HPLC analysis, it was confirmed that the content of α-cyperone was 5.243%. In order to verify the inflammatory relief effect of the ethyl acetate fraction from C. rotundus (EAFC) and α-cyperone, it was confirmed that nitric oxide (NO) production inhibitory ability in RAW 264.7 macrophages induced an inflammatory reaction with lipopolysaccharide (LPS). Real-time qPCR analysis confirmed inhibition of mRNA expression level of inflammatory factors, IL-1β, IL-6, TNF-α, COX-2 and iNOS. As a results of conducting a clinical study using a simple cosmetic formulation containing EAFC, it was confirmed that the skin irritation stimulated by sodium lauryl sulfate (SLS) was calming and relieving itching. Through these results, it is believed that the C. rotundus can be used as a natural cosmetic ingredient that has the effect of inhibiting inflammation and relieving itching.

• The Journal of Korean Obstetrics and Gynecology
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• v.35 no.3
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• pp.1-23
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• 2022

Objectives: The purpose of this study is to evaluate anti-breast cancer and anti-inflammatory effects of Chungganhaewool-tang and Shipyeukmiyeugi-eum. Methods: MDA-MB-231 cells were used to measure cytotoxicity, Reactive oxygen species (ROS) production, protein expression amounts of Bcl-2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xl), Cytochrome C Caspase-3, Caspase-7, Caspase-9, Poly ADP-ribose polymerase (PARP), Nuclear factor erythroid-2-related factor 2 (Nrf2), Heme oxygenase-1 (HO-1) and NAD (P) H Quinone Oxidoreductase 1 (NQO1) to evaluate the anti-breast cancer effects of Chungganhaewool-tang (CHT) and Shipyeukmiyeugi-eum (SYE), and THP-1 cells, differentiated into macrophage and induced inflammation with Lipopolysaccharide (LPS), were used to measure production amounts of ROS, Nitric oxide (NO), and protein expression amounts of Inducible nitric oxide synthase (iNOS), Cyclooxygenase (COX-2), Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6) and Tumor necrosis factor-alpha (TNF-α) to evaluate the anti-inflammatory effects of CHT and SYE. Results: CHT and SYE reduced MDA-MB-231 cell counts, increased protein expression of Bax and Cytochrome C, and decreased protein expression of Bcl-2, Bcl-xl. The protein expression amounts of Caspase-3, 7, and 9 decreased, but amounts of the active form, cleaved Caspase-3, 7, and 9, increased. In addition, PARP protein expression decreased, the amount of PARP protein in the cleaved form increased, and the amount of protein expressions of Nrf2 and HO-1 decreased, but NQO1 showed no significant difference. In THP-1 cells CHT and SYE reduced ROS and NO, and reduced protein expressions of iNOS, COX-2, IL-1, and TNF-α, but only SYE groups reduced IL-6. Conclusions: This study suggests that CHT and SYE have potential to be used as treatments for breast cancer.

• The Korea Journal of Herbology
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• v.28 no.3
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• pp.53-60
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• 2013

Objectives : DojukSan is known to be effective for treating a urinary diseases and stomatitis. However, there has been a lack of studies regarding the effects of Dojuksan on the inflammatory activities and effector inflammatory disease mechanism about macrophage before is not known. To elucidate the molecular mechanisms of Dojuksan water extract (DJS) on pharmacological and biochemical actions in inflammation, we examined the effect of DJS on pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated macrophages. Methods : In the present study, pro-inflammatory cytokine production was determined by performing enzyme-linked immunosorbent assay, reverse transcription polymerase chain reaction, and western blot analysis to measure the activation of MAPKs. Cells were treated with 200 ng/mL of LPS 1 h prior to the addition of DJS. Cell viability was measured by MTS assay. The investigation focused on whether DJS inhibited nitric oxide (NO) and prostaglandin E2 ($PGE_2$) productions, as well as the expressions of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6) and mitogen-activated protein kinases (MAPKs) in LPS-stimulated RAW 264.7 cells. Results : We found that DJS inhibited LPS-induced NO, $PGE_2$ and IL-6 productions as well as the expressions of iNOS and COX-2. Furthermore, DJS suppressed the LPS-induced phosphorylation of p38 MAPK and c-Jun NH2-protein kinase (JNK). Conclusions : These results suggest that DJS has inhibitory effects on LPS-induced $PGE_2$, NO, and IL-6 production, as well as the expressions of iNOS and COX-2 in the murine macrophage. These inhibitory effects occur through blockades on the MAPKs phosphorylation.

• Journal of Life Science
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• v.19 no.4
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• pp.502-507
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• 2009

In modern oriental medicine, bee venom therapy is being used for aqua-acupuncture to relieve pain and to cure inflammatory diseases such as rheumatoid arthritis, osteoarthritis, and gout. Bee venom therapy has been processed and reported in many experimental studies, with regard to its effects on pain alleviation, anti-inflammation, removal of fever, anti-convulsion, suppression of tumor and immunity strengthening, etc., however, its mechanism of action, molecular targeting on prostaglandin $E_2$ ($PGE_2$) production and telomere length regulation in human cancer remains unclear. In this study, we investigated the effect of bee venom on the levels of cyclooxygenases (COXs) and telomere regulatory components of A549 human lung cancer cells. Bee venom-induced anti-proliferative effects of A549 cells were associated with the inhibition of human telomerase reverse transcriptase (hTERT) as well as human telomerase RNA (hTR), transcription factor c-myc and the activity of telomerase. In addition, bee venom treatment markedly decreased the levels of COX-2 mRNA and protein expression without significant changes in the expression of COX-1, which was correlated with a decrease in $PGE_2$ synthesis. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of bee venom.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.44 no.4
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• pp.427-436
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• 2018

In this study, we investigated anti-inflammatory and anti-bacterial constituents from Daucus carota var. sativa (carrot) areal parts. For the extract and solvent fractions, the anti-inflammatory activities were examined by measuring the nitric oxide (NO) production using LPS-stimulated RAW 264.7 cells. Among them, the ethyl acetate (EtOAc) fraction decreased the NO level in a dose-dependent manner. To elucidate further anti-inflammatory mechanisms, EtOAc fraction was evaluated by estimating their effects on the production of prostaglandin $E_2$ and pro-inflammatory cytokines as well as on the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). As a result, the EtOAc fraction was determined to inhibit the production of $PGE_2$, IL-$1{\beta}$, IL-6 and reduce the iNOS, COX-2 protein expression. Upon the anti-bacterial tests using Staphylococcus epidermidis and Propionibacterium acnes, n-hexane (Hex) and EtOAc fractions showed the most potent activities. Three phytochemicals were isolated form the EtOAc fraction; diosmetin (1), diosmin (2), cynaroside (3). The chemical structures of the isolated compounds were elucidated based on the spectroscopic data including $^1H$ and $^{13}C$ NMR spectra, as well as comparison of the data to the literatures. Anti-inflammatory and anti-bacterial effects were studied for the isolates. All of the compounds (1 - 3) decreased the NO production, effectively. Also, compound 3 showed anti-bacterial activity on P. acnes. Based on these results, D. carota var. sativa extract could be potentially applicable as anti-inflammatory and anti-bacterial ingredients in cosmetic formulations.