• The Korean Journal of Physiology and Pharmacology
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• v.25 no.5
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• pp.395-401
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• 2021

Extended inflammation and cytokine production pathogenically contribute to a number of inflammatory disorders. Formosanin C (FC) is the major diosgenin saponin found in herb Paris formosana Hayata (Liliaceae), which has been shown to exert anti-cancer and immunomodulatory functions. In this study, we aimed to investigate anti-inflammatory activity of FC and the underlying molecular mechanism. RAW264.7 macrophages were stimulated with lipopolysaccharide (LPS) or pretreated with FC prior to being stimulated with LPS. Thereafter, the macrophages were subjected to analysis of the expression levels of pro-inflammatory mediators, including nitric oxide (NO), prostaglandin E₂ (PGE), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6, as well as two relevant enzymes, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). The analysis revealed that FC administration blunted LPS-induced production of NO and PGE in a dose-dependent manner, while the expression of iNOS and COX-2 at both mRNA and protein levels was inhibited in LPS-stimulated macrophages pre-treated with FC. Moreover, LPS stimulation upregulated mRNA expression and medium release of TNF-α, IL-1β, and IL-6, whereas this effect was blocked upon FC pre-administration. Mechanistic studies showed that inhibitory effects of FC on LPS-induced inflammation were associated with a downregulation of IκB kinase, IκB, and p65/NF-κB pathway. Taken together, these data suggest that FC possesses an inflammation-suppressing activity, thus being a potential agent for the treatment of inflammation-associated disorders.

• Journal of Acupuncture Research
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• v.32 no.3
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• pp.83-93
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• 2015

Objectives : The purpose of this study was to evaluate whether acupuncture at $SP_6$ attenuates esophageal inflammation on refluxed-induced esophagitis. Methods : Acupuncture at $SP_6$ was stimulated by acupuncture torsion technique for 30 seconds four times every hour after an operation induced reflux esophagitis(RE), and its effects were assessed in comparison with RE rats without acupuncture, and normal rats. Results : $SP_6$ acupuncture stimulation markedly ameliorated mucosal damage in the histological evaluation. Reflux-induced esophagitis rats exhibited the down-regulation of antioxidant-related protein expression levels such as heme oxygenase-1(HO-1) in the esophagitis; however, the associated levels with $SP_6$ acupuncture stimulation were significantly higher than those in RE rats without acupuncture stimulation. Moreover, $SP_6$ acupuncture stimulation significantly reduced the expression of inflammatory proteins through mitogen-activated protein kinase(MAPK)-related signaling pathways. The increased protein expressions of inflammatory mediators, cyclooxygenase-2(COX-2) and inducible nitric oxide synthase(iNOS), by nuclear factor-kappa B(NF-kB) activation were significantly suppressed through $SP_6$ acupuncture stimulation. Conclusions : Our findings support the therapeutic evidence for $SP_6$ acupuncture stimulation alleviating the development of esophagitis via regulating inflammation through the activation of the antioxidant pathway.

• Journal of Haehwa Medicine
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• v.15 no.1
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• pp.141-160
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• 2006

The obtained results are summarized as follows 1. New findings are reporting year by year as for the study related to Anti-inflammatory mechanism of Bee Venom therapy. 2. The Anti-inflammatory effect of Bee Venom therapy is achieved through counterirritation, stimulations to adrenal cortex, immuno-regulation, antioxidation, removal of free radicals, modulation of AGP gene induction. 3. The chief components of Bee Venom related to Anti-inflammatory effect are Melittin, MCD peptide, Apamin, Adolapin etc. 4. Melittin binds to secretory phospholipase A2 and inhibits its enzymatic activity. 5. Melittin blocks neutophil O2-production. 6. MCD peptide(Peptide 401) stimulates the mast cell secrets histamine, Anti-inflammatory effect caused by this is 'conterirritation'. 7. Melittin & Apamin have an anti-inflammatory effect by inducing cortisone secretion. 8. MCD peptide & Apamin increase immunologic fuction by stimulating hypophysis & adrenal cortex and have an anti-inflammatory effect by inhibiting synthesis of prostaglandin from arachidonic acid. 9. Adolapin have an anti-inflammatory effect by inhibiting COX. 10. Bee Venom have an anti-inflammatory effect by suppressing AGP($\alpha$-acid glycoprotein). 11. Bee Venom have an anti-inflammatory effect by inhibiting NO, iNOS, PLA2, COX-2, TNF-$\alpha$, IL-1, NF-${\kappa}B$, MAP kinase.

• CELLMED
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• v.2 no.1
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• pp.9.1-9.13
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• 2012

Jeechool-Whan (JW) is a prescription of Ponciri Fructus Immaturus and Atractylodis Rhizoma Alba and improves the functions of the stomach and the spleen. Although it is said in Korean Medicine that the spleen and the stomach are the roots of the body's resistance, the meaning of 'improving the spleen and the stomach' is very comprehensive. Moreover, there are lots of drugs that are said to improve the spleen and the stomach, and the number of prescriptions using these drugs is huge. In this study, we focused on the new effect and mechanism of the JW on the ovalbumin (OVA)-induced allergic rhinitis (AR) model. The increased number of rubs and the increased levels of IgE and histamine in the OVA-sensitized mice were inhibited by JW administration. The balance of Th1/Th2 cytokine level was regulated by JW administration. The levels inflammatory proteins were decreased by JW administration in the nasal mucosa of the OVA-sensitized mice. Eosinophils and mast cells infiltration increased by OVA-sensitization was also decreased in the JW-administered mice. In addition, JW inhibited caspase-1 activity in the same nasal mucosa tissue. In activated human mast cells, JW inhibited the receptor interacting protein-2, I${\kappa}$B kinase-${\beta}$, nuclear factor-${\kappa}$B/Rel A, and caspase-1 activation. In conclusion, this study will be support the clear understanding of the concept of the spleen and the stomach in traditional Korean medicine as well as for a possibility of finding a cure for this AR in traditional medical treatments.

• IMMUNE NETWORK
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• v.13 no.6
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• pp.283-288
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• 2013

The pro-inflammatory cytokines tumor necrosis factor-${\alpha}$ (TNF${\alpha}$) and interleukin (IL)-$1{\beta}$ are crucial mediators involved in chronic inflammatory diseases. Inflammatory signal pathways regulate inflammatory cytokine expression-mediated by p38 mitogen activated protein kinase (p38MAPK). Therefore, considerable attention has been given to p38MAPK as a target molecule for the development of a novel anti-inflammatory therapeutics. BIRB 796, one of p38MAPK inhibitor, is a candidate of therapeutic drug for chronic inflammatory diseases. In this study, we investigated the effect of BIRB 796 on inflammatory cytokine productions by lipopolysaccharide (LPS) in different immune cell types. BIRB 796 reduced LPS-mediated IL-8 production in THP-1 cells but not in Raw 264.7 cells. Further analysis of signal molecules by western blot revealed that BIRB 796 sufficiently suppressed LPS-mediated phosphorylation of p38MAPK in both cell types whereas it failed to block inhibitor of kappa B (I-${\kappa}B$) degradation in Raw 264.7 cells. Taken together, these results suggest that the anti-inflammatory function of BIRB 796 depends on cell types.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.2
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• pp.270-274
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• 2011

The prevalence of atopic dermatitis has markedly increased in recent years but the mechanism has not been clearly revealed. Recent study exhibited that atopic dermatitis was exacerbated by the increase of proteinase-activated receptor (PAR)-2 expression, which activated $I{\kappa}B$ kinase --> nuclear factor kappa B. Therefore, we determined whether the allergens of dust mites induced the expression of PAR-2, intercellular adhesion molecule-1 (ICAM-1, adehision molecule), interleukins (IL)-6 in HaCaT keratocytes and which herbal 1,3-butylene glycol extracts (Mori Cortex Radicis, Sanguisorba officinalis L., Arctium lappa Linne, Torilis japonica DC, Melia azedarach Linne var. japoinca Makino) suppressed their expression. Dust mite allergen increased PAR-2, ICAM-1 and IL-6 expression in HaCaT cells in a dose-dependent manner up to $3{\mu}g/mL$ but their expression reached the plateau over the dosages. The allergen ($3{\mu}g/mL$) also secreted more cytokines such as tumor necrosis factor (TNF)-${\alpha}$ and IL-6 into the media. Among five different herbal extracts ($50{\mu}g/mL$), Mori Cortex Radicis and Sanguisorba officinalis L. suppressed the PAR-2, ICAM-1 and IL-6 expression in HaCaT cells, which was activated by dust mite allergen ($3{\mu}g/mL$) and they also reduced the secretion of TNF-${\alpha}$ and IL-6 into the media. In conclusion, Mori Cortex Radicis and Sanguisorba officinalis L. can effectively reduce the prevalence and progression of atopic dermatitis by dute mite allergen.

• Journal of Applied Biological Chemistry
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• v.65 no.2
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• pp.113-120
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• 2022

We examined the anti-inflammatory properties of Nostoc commune HCW0811 in lipopolysaccharide-stimulated RAW264.7 macrophage cells. The anti-inflammatory activity of HCW0811 on viability of treated cells was assessed by measuring the level of expression of NO, prostaglandin E₂ and pro-inflammatory cytokines, namely interleukin-1β, interleukin-6, and tumor necrosis factor-α in HCW0811 treated RAW 264.7 macrophages. HCW0811 was non-toxic to cells and inhibited the production of cytokines in a concentration-dependent manner. In addition its treatment suppressed the production of pro-inflammatory cytokines in a dose-dependent manner, and concomitantly decreased the protein expressions of inducible NO synthase and cyclooxygenase-2. Moreover, the levels of the phosphorylation of mitogen-activated protein kinase family proteins such as extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38, and nuclear factor kappa B were reduced by HCW0811. These findings suggest that the HCW0811 collected from Daejeon National Cemetery have anti-inflammatory effects, and demonstrated its efficacy in cell-based in vitro assays.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.5
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• pp.427-433
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• 2013

Receptor activator of NF-${\kappa}B$ ligand (RANKL)-induced osteoclastogenesis is accompanied by intracellular $Ca^{2+}$ mobilization in a form of oscillations, which plays essential roles by activating sequentially $Ca^{2+}$/calmodulin-dependent protein kinase, calcineurin and NFATc1, necessary in the osteoclast differentiation. However, it is not known whether $Ca^{2+}$ mobilization which is evoked in RANKL-independent way induces to differentiate into osteoclasts. In present study, we investigated $Ca^{2+}$ mobilization induced by aluminum fluoride ($AlF_4^-$), a G-protein activator, with or without RANKL and the effects of $AlF_4^-$ on the osteoclastogenesis in primary cultured mouse bone marrow-derived macrophages (BMMs). We show here that $AlF_4^-$ induces intracellular $Ca^{2+}$ concentration ($[Ca^{2+}]_i$) oscillations, which is dependent on extracellular $Ca^{2+}$ influx. Notably, co-stimulation of $AlF_4^-$ with RANKL resulted in enhanced NFATc1 expression and formation of tartrate-resistant acid phosphatase (TRAP) positive multinucleated cells. Additionally, we confirmed that mitogen-activated protein kinase (MAPK) is also activated by $AlF_4^-$. Taken together, these results demonstrate that G-protein would be a novel modulator responsible for $[Ca^{2+}]_i$ oscillations and MAPK activation which lead to enhancement of RANKL-mediated osteoclastogenesis.

• Journal of Microbiology and Biotechnology
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• v.28 no.9
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• pp.1554-1562
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• 2018

The type I interferons (IFNs) play a vital role in activation of innate immunity in response to viral infection. Accordingly, viruses have evolved to employ various survival strategies to evade innate immune responses induced by type I IFNs. For example, hepatitis E virus (HEV) encoded papain-like cysteine protease (PCP) has been shown to inhibit IFN activation signaling by suppressing K63-linked de-ubiquitination of retinoic acid-inducible gene I (RIG-I) and TANK-binding kinase 1 (TBK1), thus effectively inhibiting down-stream activation of IFN signaling. In the present study, we demonstrated that HEV inhibits polyinosinic-polycytidylic acid (poly(I:C))-induced $IFN-{\beta}$ transcriptional induction. Moreover, by using reporter assay with individual HEV-encoded gene, we showed that HEV methyltransferase (MeT), a non-structural protein, significantly decreases RIG-I-induced $IFN-{\beta}$ induction and $NF-{\kappa}B$ signaling activities in a dose-dependent manner. Taken together, we report here that MeT, along with PCP, is responsible for the inhibition of RIG-I-induced activation of type I IFNs, expanding the list of HEV-encoded antagonists of the host innate immunity.

• 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.