• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2002.05a
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• pp.109-109
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• 2002

• The Journal of Korean Medicine
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• v.40 no.3
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• pp.35-58
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• 2019

Objectives: The aim of this study was to investigate the anti-inflammatory effects of Curcuma longa rhizoma extract in an experimental rat model of osteoarthritis. Methods: Osteoarthritis was induced in rats by injecting monosodium iodoacetate (MIA) into the knee joint cavity of rats. The rats were divided into 5 groups (Normal, Control, positive comparison, low (CL) and high (CH) concentration groups). Rats in the low concentration (CL) group had MIA-induced osteoarthritis; they were treated with Curcuma longa rhizoma extract at a dose of 50mg/kg body weight. Rats in the high concentration (CH) group had MIA-induced osteoarthritis; they were treated with Curcuma longa rhizoma extract at a dose of 100mg/kg body weight. Hind paw weight distribution and ROS levels were measured. At the end of all treatments, changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and creatinine levels were analyzed. In addition, inflammatory protein levels were evaluated by western blot analysis. Results: In this study, hind paw weight distribution significantly improved in the CL and CH groups, while. Reactive oxygen species (ROS) production significantly decreased in both. The levels of ALT, AST, BUN, and creatinine did not significantly change in either group. The production of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4), $p47^{phox}$, and Ras-related C3 botulinum toxin substrate 1 (RAC1) decreased in both. Catalase, heme oxygenase-1 (HO-1) and superoxide dismutase (SOD) significantly increased in the CL and CH groups, respectively. Nuclear factor erythroid 2 (Nrf2) increased, but there were no significant differences between the experimental and control groups. Inflammatory cytokines, including nuclear factor-kappa Bp65 (NF-${\kappa}Bp65$), interleukin-1beta (IL-$1{\beta}$), and tumor necrosis factor-alpha (TNF-${\alpha}$), decreased significantly in both the CL and CH groups. Conclusions: Our results showed that Curcuma longa rhizoma extract has anti-inflammatory effects. Anti-inflammatory activity is regulated by the inhibition of inflammatory cytokines and mediators, such as NF-${\kappa}B$, therefore, it suppresses cartilage damage as well.

• The Journal of Korean Obstetrics and Gynecology
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• v.33 no.3
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• pp.40-59
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• 2020

Objectives: The purpose of this study was to investigate the anti-inflammatory effects of ethanol extracts from Forsythia viridissima Lindley's fructus and Lonicera japonica Thunberg's flos in vitro, which has been frequently used in inflammatory diseases. Methods: In this experiment, the anti-inflammatory effects of ethanol extracts from Forsythia viridissima Lindley's fructus and Lonicera japonica Thunberg's flos were evaluated by checking the following substances of LPS-activated Raw264.7 cell: Prostaglandin E₂ (PGE₂), Nitric oxide (NO), Cyclooxygenase-2 (COX-2), inducible Nitric oxide synthase (iNOS), Interlukine-1β (IL-1β), Interlukine-6 (IL-6), Tumor necrosis factor-α (TNF-α), mitogen-activated protein kinase (MAPK), Inhibitor of kappa B-α (IκBα), Nuclear factor kappa B (NF-κB). And additionally measured reactive oxygen species (ROS) and free radicals to check the antioxidant effect of ethanol extracts from Forsythia viridissima Lindley's fructus and Lonicera japonica Thunberg's flos which affect inflammatory responses. Results: As a result of measuring anti-inflammatory efficacy, PGE2, NO, IL-1β, IL-6, TNF-α production amounts were reduced in the ethanol extracts from Forsythia viridissima Lindley's fructus and Lonicera japonica Thunberg's flos groups compared with the control group, and decreased the amount of COX-2 mRNA, iNOS mRNA gene expression. Expression of MAPK (ERK, JNK, p38) pathway was decreased. Expression of IκBα was increased and NF-κB was decreased. It is demonstrated that ethanol extracts from Forsythia viridissima Lindley's fructus and Lonicera japonica Thunberg's flos, by reducing NF-κB, regulate the expression of the inflammatory genes and reduce the inflammatory mediators. Ethanol extracts from Forsythia viridissima Lindley's fructus and Lonicera japonica Thunberg's flos also decreased ROS production and free radicals, which shown to have antioxidant efficacy and influence anti-inflammatory effects. Conclusions: These data suggest that ethanol extracts from Forsythia viridissima Lindley's fructus and Lonicera japonica Thunberg's flos can be used to treat various inflammatory diseases.

• Molecules and Cells
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• v.41 no.3
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• pp.244-255
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• 2018

Low-grade pro-inflammatory state and leptin resistance are important underlying mechanisms that contribute to obesity-associated hypertension. We tested the hypothesis that Astragaloside IV (As IV), known to counteract obesity and hypertension, could prevent obesity-associated hypertension by inhibiting pro-inflammatory reaction and leptin resistance. High-fat diet (HFD) induced obese rats were randomly assigned to three groups: the HFD control group (HF con group), As IV group, and the As IV + ${\alpha}$-bungaratoxin (${\alpha}-BGT$) group (As IV+${\alpha}-BGT$ group). As IV ($20mg{\cdot}Kg^{-1}{\cdot}d^{-1}$) was administrated to rats for 6 weeks via daily oral gavage. Body weight and blood pressure were continuously measured, and NE levels in the plasma and renal cortex was evaluated to reflect the sympathetic activity. The expressions of leptin receptor (LepRb) mRNA, phosphorylated signal transducer and activator of transcription-3 (p-STAT3), phosphorylated phosphatidylinositol 3-kinase (p-PI3K), suppressor of cytokine signaling 3 (SOCS3) mRNA, and protein-tyrosine phosphatase 1B (PTP1B) mRNA, pro-opiomelanocortin (POMC) mRNA and neuropeptide Y (NPY) mRNA were measured by Western blot or qRT-PCR to evaluate the hypothalamic leptin sensitivity. Additionally, we measured the protein or mRNA levels of ${\alpha}7nAChR$, inhibitor of nuclear factor ${\kappa}B$ kinase subunit ${\beta}/nuclear$ factor ${\kappa}B$ ($IKK{\beta}/NF-KB$) and pro-inflammatory cytokines ($IL-1{\beta}$ and $TNF-{\alpha}$) in hypothalamus and adipose tissue to reflect the anti-inflammatory effects of As IV through upregulating expression of ${\alpha}7nAChR$. We found that As IV prevented body weight gain and adipose accumulation, and also improved metabolic disorders in HFD rats. Furthermore, As IV decreased BP and HR, as well as NE levels in blood and renal tissue. In the hypothalamus, As IV alleviated leptin resistance as evidenced by the increased p-STAT3, LepRb mRNA and POMC mRNA, and decreased p-PI3K, SOCS3 mRNA, and PTP1B mRNA. The effects of As IV on leptin sensitivity were related in part to the up-regulated ${\alpha}7nAchR$ and suppressed $IKK{\beta}/NF-KB$ signaling and pro-inflammatory cytokines in the hypothalamus and adipose tissue, since co-administration of ${\alpha}7nAChR$ selective antagonist ${\alpha}-BGT$ could weaken the improved effect of As IV on central leptin resistance. Our study suggested that As IV could efficiently prevent obesityassociated hypertension through inhibiting inflammatory reaction and improving leptin resistance; furthermore, these effects of As IV was partly related to the increased ${\alpha}7nAchR$ expression.

• Journal of Applied Biological Chemistry
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• v.65 no.3
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• pp.203-213
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• 2022

Abeliophyllum distichum (A. distichum, Korean endemic plant) is one genus and one species in the Oleaceae family. According to the color variation of petals and calyx, A. distichum is classified as A. distichum (white flower), A. distichum for. lilacinum (pink flowers), A. distichum for. eburneum (ivory flowers), and Okhwang 1 (golden flowers). In previous studies, bioactivities (antioxidant, anti-inflammatory, and anti-cancer) of A. distichum have been reported. We conducted a comparison of the differences in bioactive compounds and the anti-inflammatory effects on macrophages among four flowers of A. distichum (FAD). The identification and quantification of glycosides were analyzed by HPLC/PDA and LCMS. These results were shown FAD has rutin, hirsutrin, and acteoside. Antioxidant activity of FAD significantly decreased reactive oxygen species. In addition, FAD reduced the expression of pro-inflammatory mediators (nitric oxide, iNOS, and COX-2) in lipopolysaccharide-induced RAW 264.7 cells. For further study, we investigated the regulation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. In conclusion, FAD may exert anti-inflammatory effects by suppressing inflammatory mediators via regulations of NF-κB and MAPK signaling pathways. Therefore, these findings suggest that FAD is a potential resource as a preventative or therapeutic agent for inflammation.

• BMB Reports
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• v.51 no.12
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• pp.609-610
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• 2018

Glycosylation is one form of protein modification and plays a key role in protein stability, function, signaling regulation and even cancer. NleB and SseK are bacterial effector proteins and possess glycosyltransferase activity, even though they have different substrate preferences. NleB/SseKs transfer the GlcNAc sugar to an arginine residue of host proteins, leading to reduced $NF-{\kappa}B-dependent$ responses. By combining X-ray crystallography, NMR, molecular dynamics, enzyme kinetic assays and in vivo experiments, we demonstrated that a conserved HEN (His-Glu-Asn) motif in the active site plays a key role in enzyme catalysis and virulence. The lid-domain regulates the opening and closing of the active site and the HLH domain determines the substrate specificity. Our findings provide evidence for the enzymatic mechanism by which arginine can be glycosylated by SseK/NleB enzymes.

• BMB Reports
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• v.53 no.4
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• pp.218-222
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• 2020

Excessive and hyperactive osteoclast activity causes bone diseases such as osteoporosis and periodontitis. Thus, the regulation of osteoclast differentiation has clinical implications. We recently reported that dehydrocostus lactone (DL) inhibits osteoclast differentiation by regulating a nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), but the underlying mechanism remains to be elucidated. Here we demonstrated that DL inhibits NFATc1 by regulating nuclear factor-κB (NF-κB), activator protein-1 (AP-1), and nuclear factor-erythroid 2-related factor 2 (Nrf2). DL attenuated IκBα phosphorylation and p65 nuclear translocation as well as decreased the expression of NF-κB target genes and c-Fos. It also inhibited c-Jun N-terminal kinase (JNK) but not p38 or extracellular signal-regulated kinase. The reporter assay revealed that DL inhibits NF-κB and AP-1 activation. In addition, DL reduced reactive oxygen species either by scavenging them or by activating Nrf2. The DL inhibition of NFATc1 expression and osteoclast differentiation was less effective in Nrf2-deficient cells. Collectively, these results suggest that DL regulates NFATc1 by inhibiting NF-κB and AP-1 via down-regulation of IκB kinase and JNK as well as by activating Nrf2, and thereby attenuates osteoclast differentiation.

• Korean Journal of Plant Resources
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• v.32 no.6
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• pp.633-643
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• 2019

Long-term ultraviolet (UV) exposure accelerates the phenomenon of skin photo-aging by activating collagenase and elastase. In this study, we aimed to investigate the effects of a combination of grapefruit and rosemary extracts (cG&Re) on UVB-irradiated damage in HaCaT cells and dorsal mouse skin. In HaCaT cells, cG&Re recovered UVB-reduced cell viability and inhibited protein expression of mitogen-activated protein kinases (MAPKs), such as extracellular signal-regulated kinases (p-Erk), c-Jun N-terminal kinases (p-JNK), and a class of MAPKs (p-P38). Also, cG&Re suppressed UVB-induced collagen and elastin degradation by decreasing matrix metalloproteinases (MMPs) and nuclear factor kappa light chain enhancer of activated B cells (NF-κB) expression, which is a transcription factor. Similar results were observed in dorsal mouse skin. Taken together, our data indicate that cG&Re prevent UVB-induced skin photo-aging due to collagen/elastin degradation via activation of MAPKs, MMPs, and the NF-κB signaling pathway in vitro and in vivo.

• The Journal of Korean Medicine
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• v.27 no.2 s.66
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• pp.196-210
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• 2006

Objectives : This study aimed to find the curative effect of Gamitongkyutang distillate in mice with allergic rhinitis. Metbods : Forty mice were divided into four groups: the normal group, the control group (allergic rhinitis elicited group), the sample I group (Gamitongkyutang treated group after allergic rhinitis elicitation) and the sample II group (distillate of Gamitongkyutang treated group after allergic rhinitis elicitation). Indexes of AR were investigated such as the histological changes of the nasal mucosa, the changes of eosinophil count, the changes of interleukin-4(IL-4) secretion in the intranasal mucosa, the alteration of inducible nitric oxide synthase(iNOS) mRNA expression and the distribution of the nuclear factor kappa B (NF-kB). ANOVA test was used for statistical analysis (p<0.05). Results : Loss of the cilium and the mucous secretion in the sample I and II groups was rare when compared to the control group. The segment of eosinophil was significantly decreased in the sample I and II groups when compared to the control group (p<0.05). A significant decrease of IL-4 mRNA expression was observed in the sample I and II groups when compared with the control group (p<0.05). Inhibition of iNOS induced by NF-kB p50 in the sample I and II groups was significantly superior to that in the control group (p<0.05). DGT and GT didn't affect AST and ALT. Conclusions : GT was superior to DGT in the IL-4 secretion, eosinophil levels and iNOS production. However, considering the difficulty in taking herbal medicine, the DGT has a meaningful curative effect in mice with allergic rhinitis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.5
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• pp.1399-1404
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• 2005

In oriental medicine, Cheongpyehwadam-tang (CHT) has long been used for the cure of inflammatory diseases in the lung and bronchus such as bronchitis, bronchial asthma, pneumonia and tuberculosis. It's use is currently further extended for the treatment of allergic asthma. To investigate the anti-inflammatory effects of CHT, we investigated the effects of CHT on the lipopolysaccharide (LPS)-induced nitric oxide (NO) and pro-inflammatory cytokines ($TNF-{\alpha}$, IL-6, and $IL-1{\beta}$) production, and on the level of inducible nitric oxide synthase (iNOS) and proinflammatory cytokines expression in murine macrophage RAW 264.7 cells. CHT alone did not affect NO or pro-inflammatory cytokines production. In contrast, CHT inhibited LPS-induced NO and proinflammatory cytokines and the levels of LPS-induced iNOS and proinflarnmatory cytokine mRNA in a dose-dependent manner. CHT also inhibited the nuclear factor-kappa B (NF-kB) activation. Taken together, these results suggested that CHT inhibits the production of NO and pro-inflammatory cytokines in RAW 264.7 cells through blockade of NF-kB activation.