• Journal of Physiology & Pathology in Korean Medicine
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• v.34 no.1
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• pp.7-13
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• 2020

Sanyeoleumja (SY) is the traditional Korean medicinal prescription for the treatment of inflammatory diseases of eyes. In this study, the anti-inflammatory effects of SY water extract were investigated. To measure the anti-inflammatory effects of SY, we examined the productions of inflammatory factor including nitric oxide (NO), prostaglandin E2 (PGE₂), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), interleukin-1β (IL-1β) in lipopolysaccharide (LPS)-induced RAW 264.7 cells. SY inhibited NO and PGE₂ production in a dose dependent manner and decreased the protein and mRNA expression of iNOS and COX-2. Also, SY decreased the mRNA expression of interleukin-6 (IL-6) and interleukin-1β (IL-1β). In conclusion, SY downregulated LPS-induced inflammatory factor productions, which could be a clinical basis for inflammatory diseases.

• Journal of Physiology & Pathology in Korean Medicine
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• v.35 no.1
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• pp.15-21
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• 2021

Donggwaja (Benincasae Semen), the seed of Benincasa hispida (Thunb.) Cogn., has been used in Korean traditional medicine to control the body heat and water retention caused by various diseases. Both the symptoms targeted by the herbal medicine in clinic and studies with disease mouse models support the potential anti-inflammatory effect of Donggwaja. However, it is less understood how Donggwaja exerts its possible anti-inflammatory effect. Here, we present evidence that Donggwaja suppresses macrophage inflammatory reactions via expressing tumor necrosis factor a-induced protein 3 (TNFAIP3 or A20) and suppressing NF-kB activity. The ethanol extract of Donggwaja (EED) showed no toxicity when added to RAW 264.7 cells less than 100mg/ml. When treating the cells for 16 h, EED significantly suppressed the nuclear localization of NF-kB, suggesting that EED suppresses NF-kB activity. Concordantly, a semi-quantitative RT-PCR analysis showed that EED decreased the expression of prototypic pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-a, IL(interleukin)-6, and IL-1b. EED induced in RAW 264.7 cells the expression of A20, a ubiquitin modulator that suppresses inflammatory signaling cascades initiated from TLR4 and TNF and IL-1 receptors, while not affecting the induction of Nrf2, an anti-inflammatory factor that could suppress the effect of NF-kB. These results suggest that EED exerts its suppressive effect on inflammation, at least in part, by expressing anti-inflammatory factor A20 and suppressing pro-inflammatory factor NF-kB activity.

• Archives of Pharmacal Research
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• v.21 no.5
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• pp.549-554
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• 1998

Tissue factor (TF), a principal initiator of the veertebrate coagulation cascade, is expressed in organ tissues, cells and blood. TF is konwn to be induced in endothelial cells, monocytes and macrophages by inflammatory stimuli and in many pathologic conditions. By using the modified method for in vido TF activity assay, we found that turpentine oil injection as an inflamatory stimulus also induced the TF activity in lung and brain tissues of rats. And the age-related increase in Tf activity was observed in healthy rat brain tissue.

• Biomedical Science Letters
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• v.29 no.3
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• pp.137-143
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• 2023

Inflammation plays an important role in immune system's response to tissue injury and biological stimuli. However, excessive inflammation can cause tissue damage. Therefore, the development of naturally derived anti-inflammatory agents have received broad attention. In this study, we investigated the anti-inflammatory mechanism of Rubi Fructus (RF) extract on the mast cell-mediated inflammatory response. To determine the regulatory mechanism of RF in inflammatory reaction, we evaluated the effects of RF on secretion of interleukin (IL)-8, IL-6 and tumor necrosis factor (TNF)-α and activation of nuclear factor-κB (NF-κB) and caspase-1 in activated human mast cells-1 (HMC-1). The results showed that RF attenuated IL-8, IL-6 and TNF-α secretion in a concentration-dependent manner. Moreover, RF significantly attenuated caspase-1and NF-κB activation in activated HMC-1. Conclusively, the present results provide evidence that RF may be a promising agent for anti-inflammatory therapy.

• Biomedical Science Letters
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• v.29 no.2
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• pp.58-65
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• 2023

Pu-erh tea, a popular and traditional Chinese tea, possesses various health-promoting effects, including inhibiting tumor cell progression and preventing type II diabetes and neurodegenerative disorders. However, the precise anti-inflammatory mechanisms are not well understood. In present study, we elucidated the anti-inflammatory mechanism of Pu-erh tea in lipopolysaccharide (LPS)-activated RAW264.7 cells. We explored the effects of Pu-erh tea on the levels of inflammatory-related genes, including inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and prostaglandin E₂ (PGE₂) in LPS-activated RAW264.7 cells. Moreover, we investigated its regulatory effects on nuclear factor-kappa B (NF)-κB and hypoxia-inducible-factor (HIF)-1α activation. The findings of this study demonstrated that Pu-erh tea inhibited the LPS-increased inflammatory cytokines and PGE₂ release, as well as COX-2 and iNOS expression. Moreover, we confirmed that the anti-inflammatory mechanism of Pu-erh tea occurs via the inhibition of NF-κB and HIF-1α activation. Conclusively, these findings provide experimental evidence that Pu-erh tea may be useful candidate in the treatment of inflammatory-related diseases.

• 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.

• Journal of Ginseng Research
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• v.42 no.4
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• pp.496-503
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• 2018

Background: Korean ginseng (Panax ginseng) plays an anti-inflammatory role in a variety of inflammatory diseases such as gastritis, hepatitis, and colitis. However, inflammation-regulatory activity of the calyx of the P. ginseng berry has not been thoroughly evaluated. To understand whether the calyx portion of the P. ginseng berry is able to ameliorate inflammatory processes, an ethanolic extract of P. ginseng berry calyx (Pg-C-EE) was prepared, and lipopolysaccharide-activated macrophages and HEK293 cells transfected with inflammation-regulatory proteins were used to test the anti-inflammatory action of Pg-C-EE. Methods: The ginsenoside contents of Pg-C-EE were analyzed by HPLC. Suppressive activity of Pg-C-EE on NO production, inflammatory gene expression, transcriptional activation, and inflammation signaling events were examined using the Griess assay, reverse transcription-polymerization chain reaction, luciferase activity reporter gene assay, and immunoblotting analysis. Results: Pg-C-EE reduced NO production and diminished mRNA expression of inflammatory genes such as cyclooxygenase-2, inducible NO synthase, and tumor necrosis factor-${\alpha}$ in a dose-dependent manner. This extract suppressed luciferase activity induced only by nuclear factor-${\kappa}B$. Interestingly, immunoblotting analysis results demonstrated that Pg-C-EE reduced the activities of protein kinase B (AKT)1 and AKT2. Conclusion: These results suggest that Pg-C-EE may have nuclear-factor-${\kappa}B$-targeted anti-inflammatory properties through suppression of AKT. The calyx of the P. ginseng berry is an underused part of the ginseng plant, and development of calyx-derived extracts may be useful for treatment of inflammatory diseases.

• Biomolecules & Therapeutics
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• v.24 no.3
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• pp.268-282
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• 2016

In the present study, we investigated the anti-inflammatory properties of Eucommia ulmoides Oliv. Bark. (EUE) in lipopolysaccharide (LPS)-stimulated microglial BV-2 cells and found that EUE inhibited LPS-mediated up-regulation of pro-inflammatory response factors. In addition, EUE inhibited the elevated production of pro-inflammatory cytokines, mediators, and reactive oxygen species (ROS) in LPS-stimulated BV-2 microglial cells. Subsequent mechanistic studies revealed that EUE suppressed LPS-induced phosphorylation of mitogen-activated protein kinases (MAPKs), phosphoinositide-3-kinase (PI3K)/Akt, glycogen synthase $kinase-3{\beta}$ ($GSK-3{\beta}$), and their downstream transcription factor, nuclear factor-kappa B ($NF-{\kappa}B$). EUE also blocked the nuclear translocation of $NF-{\kappa}B$ and inhibited its binding to DNA. We next demonstrated that EUE induced the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and upregulated heme oxygenase-1 (HO-1) expression. We determined that the significant up-regulation of HO-1 expression by EUE was a consequence of Nrf2 nuclear translocation; furthermore, EUE increased the DNA binding of Nrf2. In contrast, zinc protoporphyrin (ZnPP), a specific HO-1 inhibitor, blocked the ability of EUE to inhibit NO and $PGE_2$ production, indicating the vital role of HO-1. Overall, our results indicate that EUE inhibits pro-inflammatory responses by modulating MAPKs, PI3K/Akt, and $GSK-3{\beta}$, consequently suppressing $NF-{\kappa}B$ activation and inducing Nrf2-dependent HO-1 activation.

• Nutrition Research and Practice
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• v.10 no.3
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• pp.251-258
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• 2016

BACKGROUND/OBJECTIVES: Several pharmacological properties of red rice extract have been reported including anti-oxidant, anti-tumor, and reduced cancer cell invasion. This study was conducted to evaluate the anti-inflammatory effects of red rice extract on the production of inflammatory mediators in lipopolysaccharide (LPS)-induced Raw 264.7 macrophages. MATERIALS/METHODS: Pro-inflammatory cytokines including tumor necrosis factor-${\alpha}$ and interleukin-6 were determined by ELISA and cyclooxygenase-2 and inducible nitric oxide synthase expression was evaluated using western blot analysis. In addition, the signaling pathway controlling the inflammatory cascade such as nuclear factor kappa B ($NF-{\kappa}B$), activator proteins-1 (AP-1), and mitogen-activated protein kinase (MAPK) was determined. RESULTS: Our results showed that red rice polar extract fraction (RR-P), but not non-polar extract fraction, inhibited interleukin-6, tumor necrosis factor-${\alpha}$, and nitric oxide production in LPS-induced Raw 264.7 cells. RR-P also reduced the expression of inflammatory enzymes, inducible nitric oxide synthase, and cyclooxygenase-2. In addition, activation of AP-1 and $NF-{\kappa}B$ transcription factor in the nucleus was abrogated by RR-P. RR-P inhibited the phosphorylation of extracellular signaling-regulated kinase 1/2, c-Jun NH2-terminal kinase, and p38 MAPK signaling responsible for the expression of inflammatory mediators in LPS-stimulated Raw 264.7 cells. Based on chemical analysis, high amounts of proanthocyanidin and catechins were detected in the RR-P fraction. However, only proanthocyanidin reduced $NF-{\kappa}B$ and AP-1 activation in LPS-activated Raw 264.7 cells. CONCLUSION: These observations suggest that the anti-inflammatory properties of RR-P may stem from the inhibition of pro-inflammatory mediators via suppression of the AP-1, $NF-{\kappa}B$, and MAPKs pathways.

• Journal of Physiology & Pathology in Korean Medicine
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• v.34 no.5
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• pp.238-244
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• 2020

Yangdan-tang (YD) is recorded as a treatment to treat exterior-related fever illness in the Korean medicine. In this study, we examined the anti-inflammatory effects of YD, using YD water extract and lipopolysaccharide (LPS)-induced RAW 264.7 cells. First of all, we measured the amount of nitric oxide (NO) and prostaglandin E2 (PGE2), the products of inflammatory metabolism. Also, we measured enzymes such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), as well as cytokines such as tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin 1 alpha (IL-1α), and interleukin 1 beta (IL-1β). YD suppressed the production of NO and PGE2 in a dose dependent manner and reduced the amount of protein and the mRNA expression of iNOS and COX-2. Also, YD reduced the mRNA expression of TNF-α, IL-6, IL-1α and IL-1β. In conclusion, YD decreased production of LPS-induced inflammatory factor, which could be a clinical basic subject for inflammatory diseases.