• 대한의생명과학회지
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• 제17권3호
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• pp.225-230
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• 2011

Indirubin is the active ingredient of Danggui Longhui Wan, a mixture of plants that is used in traditional Chinese medicine to treat chronic diseases. In this study we investigated the anti-inflammatory effects of an indirubin derivative, indirubin-3’-monoxime-5-sulphonic acid (I3M-5S, $C_{16}H_{11}N_3O_5S$). We found that I3M-5S inhibits the production of various inflammatory mediators such as nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) as well as inflammatory cytokines, tumor necrosis factor-${\alpha}$ and interleukin-6 in lipopolysaccharide (LPS) stimulated murine macrophage, RAW264.7 cells. In addition, the expression of inducible nitric oxide synthase and cyclooxygenase-2, which are essential enzymes to produce NO and $PGE_2$, respectively, was blocked by I3M-5S treatment in LPS-stimulated RAW264.7 cells. Present data suggest that I3M-5S exhibits potent anti-inflammatory activity in cultured macrophages and merit further study as potential therapeutic agents for inflammatory disorders.

• Natural Product Sciences
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• 제26권3호
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• pp.244-251
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• 2020

This study investigated therapeutic candidates with anti-inflammatory potential among traditional dietary ingredients targeting inflammatory bowel disease (IBD). Both Avena sativa and traditional fermented products, such as Korean soy paste, are popular health foods. We investigated the anti-inflammatory effects of soy paste combined with A. sativa (KDA), compared with soy paste without A. sativa (KD) by evaluating the expression of pro-inflammatory cytokines in lipopolysaccharide-stimulated RAW264.7 mouse macrophages and HT-29 human colon epithelial cells. KDA significantly inhibited the production of nitric oxide (NO) and downregulated the pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in lipopolysaccharide (LPS)-induced RAW264.7 cells. In another in vitro experiment involving LPS-stimulated HT-29 cells, KDA suppressed the levels of IL-8, which is the chemokine elevated in IBD. In addition, KDA exhibited anti-oxidative properties, such as 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) and 2,2'-azino-bis(3-ethylbenz-thiazoline-6-sulfonic acid) (ABTS) radical scavenging activity. Our findings revealed that A. sativa combined with soy paste exhibits a synergistic anti-inflammatory and anti-oxidant effect following fermentation. These results suggest that KDA may be used as a potential anti-inflammatory therapy against IBD.

• 한국미생물·생명공학회지
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• 제48권3호
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• pp.366-372
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• 2020

Since, side effects of antibiotics are frequently emphasized these days, their use is gradually diminishing, and alternative drugs are being developed. We have sought to reintroduce them as raw materials for human health as conventional 'weapons' that have been retired after their historical duties. In this study, we investigated the anti-inflammatory effects of lincomycin (LIN), on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Our findings show that LIN potently inhibited production of LPS-induced proinflammatory mediators, such as nitric oxide (NO) and prostaglandin E₂ (PGE₂), without cytotoxicity. Consistent with these findings, LIN strongly decreased protein expression levels of inducible NO synthase (iNOS) and cyclooxygenase (COX-2). Furthermore, LIN reduced pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β. To further elucidate the mechanisms of these inhibitory effects of LIN, we studied LPS-induced IκB-α degradation, and mitogen-activated protein kinase (MAPK) phosphorylation. LIN suppressed downregulation of inhibitory κB (IκB-α) degradation, and the phosphorylation of the c-Jun N-terminal kinase (JNK) pathway. Based on these results, we suggest that LIN may be considered a potential candidate as an anti-inflammatory cosmetic or a medicine for human health.

• 약학회지
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• 제48권4호
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• pp.241-246
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• 2004

Mercury is a widespread metal and consequently there are large populations that currently exposed to low levels of mercury. Endotoxin is a component of the gram-negative bacteria and promotes inflammatory responses. The present study was designed to determine the impact of mercury on lymphocytes phenotype populations and endotoxin-induced inflammatory cytokine expressions in immune organ, spleen and thymus. Male BALB/c mice were exposed continuously to 0, 0.3, 1.5, 7.5, or 37.5 ppm of mercuric chloride in drinking water for 14 days and at the end of the treatment period, lipopolysaccharide (LPS, 0.5 mg/kg) was injected intraperitoneally 2 h prior to euthanasia. The dose-range of mercury used did not cause hepatotoxicity. Mercury at 7.5 and 37.5 ppm dose-dependently decreased CD3$^{+}$ T lymphocytes in spleen; both CD4$^{+}$ and CD8$^{+}$ single positive lymphocyte populations were decreased. Exposure to 7.5 and 37.5 ppm of mercury decreased the CD8$^{+}$ T lymphocyte population in the thymus, whereas double positive CD4$^{+}$ / CD8$^{+}$ and CD4$^{+}$ thymocytes were not altered. Mercury altered LPS-induced inflammatory cytokine gene expressions such as, tumor necrosis factor $\alpha$, interferon ${\gamma}$, and interleukin-12 in spleen and thymus. Results indicated that decreases in T lymphocyte populations in immune organs and altered cytokine gene expression may contribute to the immune-modulative effects of inorganic mercury.ganic mercury.

• BMB Reports
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• 제49권4호
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• pp.232-237
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• 2016

Mulberry tree twigs (Ramulus mori) contain large amounts of oxyresveratrols and have traditionally been used as herbal medicines because of their anti-inflammatory properties. However, the signaling mechanism by which R. mori exerts its anti-inflammatory action remains to be elucidated. In this study, we observed that R. mori ethanol extracts (RME) exerted an inhibitory effect on the lipopolysaccharide (LPS)-induced production of the pro-inflammatory cytokine interleukin-6 (IL-6) in Raw264.7 macrophage cells. Additionally, RME inhibited IL-6 production by blocking the leukotriene B₄ receptor-2 (BLT2)-dependent-NADPH oxidase 1 (NOX1)-reactive oxygen species (ROS) cascade, leading to anti-inflammatory activity. Finally, RME suppressed the production of the BLT2 ligands LTB4 and 12(S)-HETE by inhibiting the p38 kinase-cytosolic phospholipase A₂-5-/12-lipoxygenase cascade in LPS-stimulated Raw264.7 cells. Overall, our results suggest that RME inhibits the 'BLT2 ligand-BLT2'-linked autocrine inflammatory axis, and that this BLT2-linked cascade is one of the targets of the anti-inflammatory action of R. mori.

• Biomolecules & Therapeutics
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• 제19권1호
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• pp.97-101
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• 2011

Cirsium japonicum var. ussuriense is known to have a variety of biological activities, including anti-inflammatory, analgesic activity and antipyretic activity. In this study we investigated the role of polyacetylene compound, 1-Heptadecene-11, 13-diyne-8, 9, 10-triol (PA) from the root of Cirsium japonicum var. ussuriense as an immune-modulator. PA was evaluated as inhibitors of some macrophage functions involved in the inflammatory process. We tested the effect of PA on the production of pro-inflammatory cytokines, interleukin-1beta (IL-$1{\beta}$) and tumor necrosis factor-alpha (TNF-$\alpha$), and nitric oxide (NO) in murine macrophage cell line, RAW264.7. There was no effect on cytokine production of macrophages by PA itself. However, PA inhibited lipopolysaccharide (LPS)-induced IL-$1{\beta}$ and TNF-$\alpha$ production by macrophages at a dose dependent manner. PA also suppressed the NO production of macrophages by LPS. LPS-induced NF-${\kappa}B$ activity was decreased by treatment of PA. Therefore, these results suggest that PA has anti-inflammatory effect by inhibiting the NF-${\kappa}B$ activation.

• 대한한의학회지
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• 제33권4호
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• pp.42-49
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• 2012

Objectives: The purpose of this study was to investigate effects of Red Ginseng-Ejung-tang Water Extract (ER) on cytokine production in RAW 264.7 mouse macrophages stimulated by lipopolysaccharide (LPS). Methods: Levels of various cytokines such as interleukin (IL)-6, IL-10, IL-2, IL-12p70, vascular endothelial growth factor (VEGF), monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-2, keratinocyte-derived chemokine (KC), tumor necrosis factor (TNF)-alpha, granulocyte macrophage colony-stimulating factor (GM-CSF) were measured by high-throughput multiplex bead array cytokine assay based on xMAP (multi-analyte profiling beads) technology. Results: ER significantly decreased levels of IL-6, IL-10, IL-2, IL-12p70, VEGF, and MCP-1 for 24 hrs incubation at the concentrations of 25, 50, and $100{\mu}g/mL$ in LPS-induced RAW 264.7 cells (P < 0.05). But ER did not exert significant effects on production of MIP-2, KC, TNF-${\alpha}$, and GM-CSF in LPS-induced RAW 264.7 cells. Conclusions: These results suggest that ER has an anti-inflammatory property related with its inhibition of cytokine production in LPS-induced macrophages.

• 생명과학회지
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• 제21권9호
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• pp.1310-1314
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• 2011

염증은 바이러스 등의 병원체 및 다양한 물리.화학적 스트레스에 의하여 일어나는 생체방어 반응이나, 과도한 염증반응은 세포독성과 다양한 질환을 일으킨다. 따라서 염증반응에서 생성되는 과도한 염증매개물질들을 억제함으로 다양한 염증질환을 예방, 치료 할 수 있다. 본 연구에서는 Tylophora asthmatica, Tylophora ovata 등에 함유되어 있는 생리활성 성분인 septicine의 항염증 효과를 연구하였다. 생쥐의 대식세포주인 RAW264.7 세포에 lipopolysaccharide (LPS)를 처리하여 염증반응을 유도하고, septicine를 처리한 결과, septicine은 LPS 처리에 의한 nitric oxide (NO) 및 염증성 사이토카인의 분비를 현저히 억제시키는 것을 관찰 할 수 있었으며, NO의 생합성효소인 iNOS 단백질의 발현 또한 억제시킴을 확인 할 수 있었다. 이러한 연구결과는 염증반응을 조절하는 후보물질로써의 septicine의 가능성을 보여주는 것이다.

• Journal of Animal Science and Technology
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• 제63권5호
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• pp.1159-1168
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• 2021

Ovotransferrin (OTF), an egg protein known as transferrin family protein, possess strong antimicrobial and antioxidant activity. This is because OTF has two iron binding sites, so it has a strong metal chelating ability. The present study aimed to evaluate the improved immune-enhancing activities of OTF hydrolysates produced using bromelain, pancreatin, and papain. The effects of OTF hydrolysates on the production and secretion of pro-inflammatory mediators in RAW 264.7 macrophages were confirmed. The production of nitric oxide (NO) was evaluated using Griess reagent and the expression of inducible nitric oxide synthase (iNOS) were evaluated using quantitative real-time polymerase chain reaction (PCR). And the production of pro-inflammatory cytokines (tumor necrosis factor [TNF]-α and interleukin [IL]-6) and the phagocytic activity of macrophages were evaluated using an ELISA assay and neutral red uptake assay, respectively. All OTF hydrolysates enhanced NO production by increasing iNOS mRNA expression. Treating RAW 264.7 macrophages with OTF hydrolysates increased the production of pro-inflammatory cytokines and the phagocytic activity. The production of NO and pro-inflammatory cytokines induced by OTF hydrolysates was inhibited by the addition of specific mitogen-activated protein kinase (MAPK) inhibitors. In conclusion, results indicated that all OTF hydrolysates activated RAW 264.7 macrophages by activating MAPK signaling pathway.

• International Journal of Oral Biology
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• 제46권1호
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• pp.51-59
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• 2021

Periodontal disease is an inflammatory disease that affects the destruction of the bone supporting the tooth and connective tissues surrounding it. Periodontal ligament fibroblasts (PDLFs) induce overexpression of matrix metalloproteinase (MMP) involved in periodontal disease's inflammatory destruction. Osteoclasts take part in physiological bone remodeling, but they are also involved in bone destruction in many kinds of bone diseases, including osteoporosis and periodontal disease. This study examined the effect of baicalin on proteolytic enzymes' production and secretion of inflammatory cytokines in PDLFs and RAW 264.7 cells under the lipopolysaccharide (LPS)-induced inflammatory conditions. Baicalin inhibited the expression of the protein, MMP-1 and MMP-2, without affecting PDLFs' cell viability, suggesting its possibility because of the inhibition of phosphorylation activation of mitogen-activated protein kinase's p38, and the signal transduction process of nuclear factor κB (NFκB)-related protein. Also, baicalin reduced the expression of MMP-8 and MMP-9 in RAW 264.7 cells. This reduction is thought to be due to the inhibition of the signal transduction process of NFκB-related proteins affected by inhibiting p65RelA phosphorylation. Also, baicalin inhibited the secretion of nitric oxide and interleukin-6 induced by LPS in RAW 264.7 cells. These results suggest that baicalin inhibits connective tissue destruction in periodontal disease. The inhibition of periodontal tissue destruction may be a therapeutic strategy for treating inflammatory periodontal-diseased patients.