• Molecules and Cells
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• v.23 no.3
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• pp.398-404
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• 2007

Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) are involved in various pathophysiological processes such as inflammation and carcinogenesis. In a search for inhibitors of COX-2 and iNOS production we found that extracts of Stewartia koreana strongly inhibited NO and $PGE_2$ production in LPS-treated macrophage RAW 264.7 cells. We have now shown that the mRNA and protein levels of iNOS and COX-2 are reduced by the Stewartia koreana extract (SKE). SKE inhibited expression of an NF-${\kappa}B$ reporter gene in response to LPS, and gel mobility shift assays revealed that SKE reduced NF-${\kappa}B$ DNA-binding activity. The extract also inhibited LPS-induced phosphorylation of $I{\kappa}B-{\alpha}$ and nuclear translocation of p65. Administration of the extract reduced the symptoms of arthritis in a collagen-induced arthritic mouse model. These results indicate that Stewartia extracts contain potentially useful agents for preventing and treating inflammatory diseases.

• BMB Reports
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• v.52 no.2
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• pp.145-150
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• 2019

Endothelial dysfunction-induced lipid retention is an early feature of atherosclerotic lesion formation. Apoptosis of vascular smooth muscle cells (VSMCs) is one of the major modulating factors of atherogenesis, which accelerates atherosclerosis progression by causing plaque destabilization and rupture. However, the mechanism underlying VSMC apoptosis mediated by endothelial dysfunction in relation to atherosclerosis remains elusive. In this study, we reveal differential expression of several genes related to lipid retention and apoptosis, in conjunction with atherosclerosis, by utilizing a genetic mouse model of endothelial nitric oxide synthase (eNOS) deficiency manifesting endothelial dysfunction. Moreover, eNOS deficiency led to the enhanced susceptibility against pro-apoptotic insult in VSMCs. In particular, the expression of aggrecan, a major proteoglycan, was elevated in aortic tissue of eNOS deficient mice compared to wild type mice, and administration of aggrecan induced apoptosis in VSMCs. This suggests that eNOS deficiency may elevate aggrecan expression, which promotes apoptosis in VSMC, thereby contributing to atherosclerosis progression. These results may facilitate the development of novel approaches for improving the diagnosis or treatment of atherosclerosis.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.23 no.2
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• pp.109-124
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• 2010

Objectives : The aim of this study is to investigate the antiallergic effects of YTT on allergic rhinitis by regulation of peroxisome proliferator-activated receptor gamma (PPAR-$\gamma$). Methods : The thirty rats were divided into three groups : normal group, control (allergic rhinitis elicited) group, sample (Yeotaectonggi-tang treated after allergic rhinitis elicitation) group. To induce allergic rhinitis in control group and sample group, rats were sensitized intraperitoneally with 0.1% ovalbumin(OVA) solution 3 times at intervals of 1 week. Then intranasal sensitization was performed by diffusing 0.1% ovalbumin(OVA) solution 3 times at intervals of 2 days. After that time rats in sample group were oral administration treated by YTT for 7days. The change of the amounts of eosinophil, substance P, MIP-2, PPAR-$\gamma$, IL-4, iNOS were observed in each group. we used the statistical method of ANOVA test(p<0.05). Results : The number of eosinophil in sample group noticeably decreased than control group. And the decrease of substance P and MIP-2 positive reaction were observed in mucosa. YTT inhibited IL-4 and iNOS production, mucus secretion, activation of mast cells and fibrosis remodeling by regulation of PPAR-$\gamma$ activation. Conclusion : According to the above results, it is considered that YTT mitigated mucosa damage on the mice model with allergic rhinitis by regulation of PPAR-$\gamma$.

• Journal of Acupuncture Research
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• v.37 no.2
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• pp.123-127
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• 2020

Background: This study was designed using a mouse model of atopic dermatitis [phthalic anhydride (PA)-treated mice], to investigate the anti-inflammatory effect of bee venom pharmacopuncture (BVP) in keratinocytes. Methods: Western blot analysis was performed to investigate inflammation related protein expression of iNOS, COX-2, phospho-ERK (p-ERK), and ERK, in LPS (1 ㎍/mL)-activated keratinocytes, following BVP treatment, and in PA-treated mice, after BVP treatment. Griess reaction was performed to investigate NO concentration. Enzyme-linked immunosorbent assays were used to determine the concentrations of interleukin (IL)-4+, IL-17A+, IL-13 and IL-4 in PA-treated mice after BVP treatment. In addition, monocyte, macrophage, neutrophil, and eosinophil counts were measured to observe the changes in white blood cell infiltration. Results: The keratinocytes of the BVP-treated group showed a decreased expression of iNOS, COX-2, ERK at 5 OX-2, ERK E, and p-ERK at 1, 2 and 5 RKRK ERK ERK, and a dose-dependent decrease in NO concentration at 2 and 5 ntrationof s. In the BVP-treated groups (0.1 μ.1-trea μ.1-treated gr), PA-treated mice showed recovery after 4 weeks which was dose-dependent, showing a significant decrease in clinical scores for AD, and a decreased concentration of IL-13 and IL-4 with BV treatment. There was a dose-dependent decrease in the infiltration of eosinophils, neutrophils, monocytes, macrophages, and a decreased thickness of the epidermis due to inflammation, and decreased expressions of iNOS, COX-2, p-ERK, ERK, especially in the 0.1 μ0/mL BVP-treated group, Conclusion: These results suggest that BVP may be an effective alternative treatment for atopic dermatitis.

• Natural Product Sciences
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• v.20 no.2
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• pp.113-118
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• 2014

Ribes fasciculatum which belongs to Saxifragaceae has been widely used as a traditional medicine for the treatment of symptoms associated with lacquer poison. However, pharmacological studies on the R. fasciculatum are extremely limited until now. Thus, in this study, we evaluated the possible anti-inflammatory effects of ethyl acetate fraction of R. fasciculatum (ERF) using IFN-${\gamma}$/LPS-stimulated peritoneal macrophage model. We investigated the change in nitrite level in the absence or presence of ERF after LPS stimulation, and we found that ERF effectively attenuates the NO production in a dose dependent manner without notable toxicity. To determine the mechanism of the inhibitory action of ERF on NO production, we performed iNOS enzyme activity assay and Western blotting. Here we showed that both of iNOS enzyme activities and iNOS expressions were significantly down-regulated by ERF, indicating that these dual activities of ERF are responsible for ERF-mediated NO suppression. In addition, ERF inhibitied the expression of cyclooxygenase-2 (COX-2), an another key enzyme in inflammation through suppression of NF-${\kappa}B$ activation. We also tested anti-inflammatory properties of ERF not only in vitro, but in vivo using trypsin-induced paw edema model in mice. Our results revealed that the increased paw volume in response to trypsin injection was recovered by ERF supplement dose dependently.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.15 no.8
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• pp.5088-5094
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• 2014

Hovenia dulcis extract (HDE) has positive effects on alcohol degradation, recovery of liver damage and antioxidant activities. This study examined whether HDE exerts an ameliorative effect on inflammatory orifacial pain in an animal algesic model with formalin. The animals (rats) were divided into four groups: group I (control), group II (right facial subcutaneous injection of 5% formalin, inflammatory orifacial pain group), group III (5% formalin + distilled water administration), and group IV injection (5% formalin + 4.5 ml/kg of HDE), respectively. The scores from the scratch and effleurage tests were applied to evaluate the differences between three groups. The expression of p38 MAPK, iNOS and Nrf2 in the brain and medulla oblongata, which are involved in pain regulation, inflammation, antioxidation and nitric oxide production, were analyzed by western blot. The degree of orifacial pain was significantly lower in group IV than in groups I, II and, III. The expression of p38MAPK, iNOS and Nrf2 in the brain and medulla were also lower in group IV than in the other groups. These findings suggested that a Hovenia dulcis extract can attenuate inflammatory orifacial pain by suppressing the expression of p38 MAPK, iNOS and Nrf2.

• The Journal of Korean Medicine
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• v.32 no.6
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• pp.18-29
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• 2011

Objectives: To investigate anti-inflammatory and anti-arthritic effects of Gyulpidaehwangbakcho-tang (GDBT) extract in a murine model of rheumatoid arthritis. Methods: The mice received $100{\mu}g$ of bovine type II collagen in Freund's complete adjuvant by intradermal injection at the base of the tail on day 0 and a booster injection on day 21. The mice were orally administered with GDBT (200 or 50mg/kg dissolved in distilled water) daily from day 1 to day 21 after arthritis incidence, and monitored for disease incidence and the severity of arthritis up to day 21. In order to evaluate the effect of GDBT on disease progression, we examined pro-inflammatory cytokines including IL-$1{\beta}$, IL-6, TNF-${\alpha}$, COX-2 and NOS-II. Results: GDBT produced a significant and dose dependent inhibition of arthritis and inflammation during the entire duration of the study. This action was characterized by the decreased production of IL-$1{\beta}$, IL-6, TNF-${\alpha}$, COX-2, and NOS-II in vivo. Conclusion: We believe that the anti-arthritic activity of GDBT is due to its modulatory effect on the expression of pro-inflammatory cytokine in the synovium. Our results contribute towards validation of the traditional use of GDBT in the treatment of RA and other inflammatory joint disorders.

• Journal of TMJ Balancing Medicine
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• v.9 no.1
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• pp.4-11
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• 2019

Objectives: Although intraoral balancing appliance therapy has been used effective to several diseases, verification studies through cerebral diseases are poorly reported so far. Thus we investigated the effect of tooth-cut induced dental malocclusion against mouse model of ischemic stroke. Methods: Tooth-cut and 90 min middle cerebral artery occlusion (MCAO) were loaded to C57BL/6 male mice, and total infarct area, neurological deficit scores (NDS), histological change of hippocampal region were observed. Production levels of reactive oxygen species (ROS) and inducible nitric oxide synthase (iNOS) in cerebral tissue were also measured. Results: The longer the tooth-cut period, the greater the area of cerebral infarction caused by MCAO, and NDS began to increase as the tooth was cut, and the results were more negative when MCAO was loaded. Histological change of hippocampal cells was significant when tooth-cut was maintained for 7 days. Those damages were thought to depend on the generation of ROS and iNOS in brain tissue. Conclusions: Since tooth-cut increased total area of cerebral infarction due to MCAO in mice, it is able to be confirmed that anomaly of the temporomandibular occlusion can affect neurological diseases.

• Korean Journal of Plant Resources
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• v.19 no.6
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• pp.670-676
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• 2006

Tea polysaccharide had high antioxidant activity and it could be used to cure diabetes. Antioxidant activity of tea poly-saccharide (TPS) from three kinds of tea (green tea, oolong tea and black tea) were compared, the result indicated that oolong tea polysaccharide (OTPS) had the highest antioxidant activity. In order to explicate the mechanism of antioxidant and hypoglycemic activity, the streptozotocin (STZ)-induced diabetes mice model (DM) was established. The influence of OTPS on blood-glucose, content of MDA and NO, and activities of GSH-PX, SOD, NOS in serum, kidney and liver were investigated. The result showed that after four weeks injection of OTPS to DM mice, the blood-glucose of three treatment group reduced by 14.5%,21.5% and 33.3%, respectively, comparing to the model control. The reduction effect of OTPS increased with the rise of dose. The activity of SOD and GSH-PX elevated significantly, while the activity of NOS decreased. The content of MDA and NO reduced significantly. The above results imply that antioxidant activity was enhanced. Comparing to XKW treatment, the effect of a dose of 300mg/(kg. bw) OTPS was much better. The research showed that the OTPS had a significant effect on reducing blood glucose, and could enhance the antioxidant activity of DM mice.

• Korean Journal of Acupuncture
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• v.22 no.2
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• pp.57-74
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• 2005

Objective : Frutus gardeniae, seed of Gardenia jasminoides Ellis is one of the crude drugs used for the treatment of inflammatory condition in oriental medicine. Methodes : The present study aimed to examine the analgesic effect and anti-inflammatory effect of Frutus gardeniae extract (FGE) on a rat model of ankle sprain pain, and the relations between FGE-induced effect and endogenous nitric oxide (NO) and inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2), and c-Fos protein expression in the spinal cord. As a chronic pain model, ankle sprain pain model was used to test the effect of FCE injection applied to acupuncture point. After the induction of ankle sprain, rats subsequently showed a reduced stepping force of the affected limb for at least the next 4 days. The reduced stepping force of the limb was presumably due to a painful knee. FGE dissolved in normal saline was injected several acupoints. Results : After the treatment, behavioral tests measuring stepping force were periodically conducted during the next 8 hours. FGE produced significant improvement of stepping force of the hindlimb affected by the ankle sprain lasting at least 4 hours. FGE produced the improvement of stepping force of the affected hindlimb in a dose-dependent manner. In addition, FGE injection showed inhibitory effect on the paw edema induced by ankle sprain. Both NO production and iNOS, COX-2 protein expression increased by ankle sprain were suppressed by FGE. FGE on combination with electroacupuncture (EA) produced more powerful and longer lasting improvement of stepping force of the hindlimb affected by the ankle sprain than either FGE or EA did. The present study suggest that FGE produces a potent analgesic effect on the ankle sprain pain model of the rat and that FGE-induced analgesia modulate endogenous NO through the suppression of iNOS/COX-2 protein expression.