• Journal of Life Science
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• v.31 no.12
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• pp.1110-1119
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• 2021

The purpose of this study was to investigate whether the inflammatory response in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages could be promoted by particulate matter 2.5 (PM_2.5) stimulation. To this end, the levels of inflammatory parameters, reactive oxygen species (ROS) and inflammation-regulating genes were investigated in RAW 264.7 cells treated with PM_2.5 in the presence or absence of LPS. Our results showed that the production levels of pro-inflammatory mediators (nitric oxide and prostaglandin E₂) and cytokines (interleukin-6 and -1β) were significantly increased by PM_2.5 stimulation in LPS-treated RAW 264.7 cells, which was correlated with increased expression genes involved in their production. In addition, when LPS-treated RAW 264.7 cells were exposed to PM_2.5, nuclear factor-kappaB (NF-κB) expression was further increased in the nucleus, and the expression of inhibitor of NF-κB as well as NF-κB in the cytoplasm was decreased. These results suggest that the co-treatment of PM_2.5 and LPS further increases the activation of the NF-κB signaling pathway compared to each treatment alone, thereby contributing to the promotion of transcriptional activity of inflammatory genes. Furthermore, although the generation of ROS was greatly increased by PM_2.5 in LPS-treated RAW 264.7 cells, the NF-κB inhibitor did not reduce the generation of ROS. In addition, when the generation of ROS was artificially suppressed, the production of inflammatory mediators and the activation of NF-κB were both abolished. Therefore, our results suggest that the increase in the NF-κB-mediated inflammatory response induced by PM_2.5 in LPS-treated RAW 264.7 macrophages was a ROS generation-dependent phenomenon.

• IMMUNE NETWORK
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• v.8 no.1
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• pp.13-20
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• 2008

Background: Coptis chinensis rhizome has been used as a medicinal herb in traditional Oriental medicine. We investigated the effects of Coptis chinensis extract on inflammatory mediators and delayed type hypersensitivity in mice. Methods: The inhibitory effect of ethanolic extract of Coptis chinensis (CCE) on cell proliferation was evaluated using MTS assay. The lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and the Con A-activated mouse splenocytes were cultured with various concentrations of CCE. Total nitric oxide (NO) production was determined by Griess reaction. The amounts of secreted prostaglandine E2 ($PGE_2$), interleukin (IL)-2 and IFN-${\gamma}$ were measured by ELISA. To investigate the in vivo anti-inflammatory effect of CCE, oxazolone-induced delayed type hypersensitivity (DTH) model was used. Results: The CCE at $100{\mu}g/ml$ significantly blocked the LPS-induced production of pro-inflammatory mediators (NO and PGE) in RAW264.7 macrophages. Also, it significantly inhibited cell proliferation and cytokine (IL-2 and IFN-${\gamma}$) production in splenocytes. Furthermore, when splenocytes from CCE fed mice (200 mg/kg for 2 weeks) were activated with Con A, cell proliferation and cytokine production were significantly inhibited. In addition, CCE decreased in vivo inflammation in oxazolone-induced DTH model mice. Conclusion: We suggest that Coptis chinensis can be used as an anti-inflammatory drug by exerting an inhibitory effect in inflammatory mediator- and cell-mediated inflammation.

• Physical Therapy Rehabilitation Science
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• v.6 no.4
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• pp.170-175
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• 2017

Objective: The anti-inflammatory effects of low-level laser in burn wound model in rats were investigated. Design: Randomized controlled trial. Methods: The rats were assigned to three experimental groups. Group I received second-degree burn wounds; Group II received dressing film and low-level laser ($1.2J/cm^2$) treatment after a burn wound; Group III received dressing film and low-level laser ($2.3J/cm^2$) treatment after a burn wound. After inducing a deep second-degree burn wound, the wound was observed every day and the burn area diameter and retraction quantification at 1, 7, and 14 days were evaluated. Low-level laser was investigated on hematological parameters after 14 days. Effects of low-level laser on the inflammatory cytokines (tumor necrosis $factor-{\alpha}$ [$TNF-{\alpha}$] and interleukin-6 [IL-6]) concentrations in the serum were evaluated using immunosorbent assay kits. Results: Group III showed a significant difference in wound size on days 7 and 14 compared to Group I (p<0.05). Group II showed a significant difference in wound size on day 14 compared to Group I (p<0.05). For wound contraction percentage, both laser therapy treatment groups showed a significant difference compared with Group I (p<0.05). There was also a significant difference in wound contraction percentage in Group III compared to Group II (p<0.05). Compared with the model control group, decreased $TNF-{\alpha}$ and IL-6 levels in the serum was observed at 14 days after burn wound induction. Conclusions: The results of this study suggest that low-level laser therapy can assist in burn wound healing, which might be associated with decreased concentrations of $TNF-{\alpha}$ and IL-6 related proinflammatory cytokines.

• Biomolecules & Therapeutics
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• v.24 no.4
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• pp.387-394
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• 2016

Sepsis, a serious clinical problem, is characterized by a systemic inflammatory response to infection and leads to organ failure. Toll-like receptor (TLR) signaling is intimately implicated in hyper-inflammatory responses and tissue injury during sepsis. Histone deacetylase (HDAC) inhibitors have been reported to exhibit anti-inflammatory properties. The aim of this study was to investigate the hepatoprotective mechanisms of trichostatin A (TSA), a HDAC inhibitor, associated with TLR signaling pathway during sepsis. The anti-inflammatory properties of TSA were assayed in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Polymicrobial sepsis was induced in mice by cecal ligation and puncture (CLP), a clinically relevant model of sepsis. The mice were intraperitoneally received TSA (1, 2 or 5 mg/kg) 30 min before CLP. The serum and liver samples were collected 6 and 24-h after CLP. TSA inhibited the increased production of tumor necrosis factor (TNF)-${\alpha}$ and interleukin (IL)-6 in LPS-stimulated RAW264.7 cells. TSA improved sepsis-induced mortality, attenuated liver injury and decreased serum TNF-${\alpha}$ and IL-6 levels. CLP increased the levels of TLR4, TLR2 and myeloid differentiation primary response protein 88 (MyD88) protein expression and association of MyD88 with TLR4 and TLR2, which were attenuated by TSA. CLP increased nuclear translocation of nuclear factor kappa B and decreased cytosolic inhibitor of kappa B ($I{\kappa}B$) protein expression, which were attenuated by TSA. Moreover, CLP decreased acetylation of $I{\kappa}B$ kinase (IKK) and increased association of IKK with $I{\kappa}B$ and TSA attenuated these alterations. Our findings suggest that TSA attenuates liver injury by inhibiting TLR-mediated inflammatory response during sepsis.

• The Korea Journal of Herbology
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• v.30 no.1
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• pp.85-93
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• 2015

Objectives : Bilobalide (BIL) is a predominant sesquiterpene trilactone constituent that accounts for a partial portion of the standardized Ginkgonis Folium extract, which has been widely used to treat a variety of neurological disorders involving cerebral ischemia and neurodegeneration. In this study, it was tested whether BIL exhibits anti-inflammatory activities on inflammation response, or not. Methods : To elucidate the molecular mechanisms of BIL on pharmacological and biochemical actions in inflammation, we examined the effect of BIL on pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated macrophages. The investigation was focused on how BIL affect on inflammation-related mediators including various signals such as nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$), inducible NO synthase(iNOS), cyclooxygenase-2(COX-2), interleukin-6(IL-6), tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), mitogen-activated protein kinases(MAPKs) and nuclear factor kappa-light-chain-enhancer of activated B cells ($NF-{\kappa}B$) in LPS-stimulated RAW 264.7 cells. Results : We found that BIL inhibited LPS-induced NO, $PGE_2$, IL-6 and $TNF-{\alpha}$ productions as well as the expressions of iNOS and COX-2. Furthermore, BIL suppressed the LPS-induced phosphorylation for MAPK activation. Conclusions : These results suggest that BIL has inhibitory effects on LPS-induced $PGE_2$, NO, IL-6 and $TNF-{\alpha}$ production, as well as the expressions of iNOS and COX-2 in the murine macrophage. It seems that these inhibitory effects occur by blocking the phosphorylation of MAPKs for activation. Then, BIL suppressed the activation of nuclear factor $NF-{\kappa}B$ in nucleus. These observations suggest that BIL has anti-inflammatory effect by inhibiting.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.32 no.4 s.59
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• pp.263-267
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• 2006

Antioxidative and anti-inflammatory activities of Petasites japonicus extract were evaluated. P. japonicus extract showed 70.1% inhibition on peroxidation of linoleic acid. In the experiment using the cell permeable dye, 2',7'- dichlorofluorescein diacetate (DCFDA) as an indicator of reactive oxygen species (ROS) generation, intracellular oxidative stress in UVB-irradiated keratinocytes was shown to be decreased by P. japonicus extract. Also, UVB-induced production of interleukin-$1{\alpha}$ and prostaglandin $E_2$ in human HaCaT keratinocytes was reduced in a dose-dependent manner by treatment with P. japonicus extract. All these results suggest that P. japonicus extract can be effectively used for prevention of UV-induced adverse skin reactions such as radical production and inflammation.

• International Journal of Advanced Culture Technology
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• v.7 no.4
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• pp.156-162
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• 2019

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by progressive joint deterioration; Furthermore, RA can also affect body tissues, including the skin, eyes, lungs, heart and blood vessels. The early stages of RA can be difficult to diagnose because the signs and symptoms mimic those of many other diseases. It is not known exactly what triggers the onset of RA and how to cure the disease. But recent discoveries indicate that remission of symptoms is more likely when treatment begins early with strong medications known as disease-modifying anti-rheumatic drugs (DMARDs). Tumor necrosis factor (TNF) inhibitors are typical examples of biotherapies that have been developed for RA. The substances may occur naturally in the body or may be made in the laboratory. Other biological therapies care biological response modifiers (BRMs)such as monoclonal antibodies, interferon, interleukin-2 (IL-2) and a protein binder using repeat units. These substances play significant anti-inflammatory roles. Proteins with recurrent, conserved amino acid stretches mediate interactions among proteins for essential biological functions; for example, ankyrin (ANK), Heat repeat protein (HEAT), armadillo repeat protein (ARM) and tetratricopeptide repeats (TPR). Here, we describe Leucine rich repeats (LRR) that ideally fold together to form a solenoid protein domain and is more applicable to our current study than the previously mentioned examples. Although BRMs have limitations in terms of immunogenicity and effector functions, among other factors, in the context therapeutic use and for proteomics research, We has become clear that repeat-unit-derived binding proteins will increasingly be used in biotechnology and medicine.

• The Journal of Korean Obstetrics and Gynecology
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• v.27 no.1
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• pp.1-16
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• 2014

Objectives: The purpose of this study was to investigate the effects of Gardeniae Fructus Water Extract (GF) on the production of inflammatory mediators in RAW 264.7 cell treated with lipopolysaccharide (LPS). Methods: Gradeniae Fructus was extracted with distilled water (2,000 ml) for 2 hours. In order to evaluate cytotoxicity of GF, 3 - (4,5-dimethylthiazol-2-yl) - 2,5 - diphenyltetrazolium bromide (MTT) assay was performed. To investigate antiinflammatory effects, the concentration of nitric oxide (NO) was measured with No assay, calcium (Ca) was measured with Fluo-4 Ca assay, and cytokine was measured by Bio-Plex cytokine assay in RAW 264.7 cell. And when p-value is below 0.05, it is judged to have the significant difference statistically. Results: 1. GF did not show any cytotoxicity. 2. GF suppressed the production of NO and Ca at the concentration of 25, 50, 100 and $200{\mu}g/ml$. 3. GF suppressed the production of interleukin (IL)-$1{\beta}$, IL-10, IL-12p40, macrophage-colony stimulating factor (M-CSF), macrophage inflammatory protein (MIP)-$1{\beta}$ and keratinocyte chemoattractant(KC) at the concentration of 25, 50, 100 and $200{\mu}g/ml$. 4. GF suppressed the production of vascular endothelial growth factor (VEGF), granulocyte-colony stimulating factor (G-CSF) and monocyte cheomattractant protein (MCP)-1 at the concentration of 25, 50 and $100{\mu}g/ml$. 5. GF suppressed the production of granulocyte macrophage-colony stimulating factor (GM-CSF) and regulated on activation, normal T cell expressed and secreted (RANTES) at the concentration of 25 and $50{\mu}g/ml$. 6. GF suppressed the production of MIP-2 at the concentration of 50 and $100{\mu}g/ml$, and tumor necrosis factor (TNF)-${\alpha}$ at the concentration of 50 and $200{\mu}g/ml$. Conclusions: These results suggest that GF has anti-inflammatory effect and immuno-modulating activity.

• Korean Journal of Medicinal Crop Science
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• v.28 no.6
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• pp.471-480
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• 2020

Background: The roots of Cirsium japonicum var. ussuriense (RCJ) have been used as traditional medicine in Korea for hematuria and hematemesis. These extracts exert anti-oxidative and anti-inflammatory effects by scavenging for free radical and regulating the inflammatory response. However, the effect of RCJ on rheumatoid arthritis (RA) has not been elucidated. Thus, we evaluated the water extract of RCJ (WRCJ) using type II collagen-induced RA models. Methods and Results: RA was induced by immunization with type II collagen. All experimental materials were orally administered daily for three weeks. The positive control group was administered with 0.2 mg/kg methotrexate (n = 7), while the experimental group was administered with WRCJ (100 or 500 mg/kg, n = 7). Serum levels of TNF-alpha, Interleukin 6 (IL-6), and type II collagen IgG (CII) were measured using ELISA. Administration of 500 mg/kg WRCJ decreased the levels of TNF-alpha, IL-6, and CII. Moreover, WRCJ treatment diminished swelling of hind legs and infiltration of inflammatory cells in RA models' synovial membrane. Conclusions: These results indicate that WRCJ could improve RA, reduce inflammatory indicators and synovial inflammation. However, further experiments are required to determine how WRCJ can influence the signal transduction pathway in RA.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.9
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• pp.1333-1339
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• 2011

After mulberry (Morus alba) leaves were fermented with Hericium erinaceum mycelium by solid-state culture to enhance physiological activity, fermented mulberry leaves (MA-HE) was extracted by hot-water (MA-HEHW) and ethanol (MA-HE-E). MA-HE-HW showed enhanced mitogenic and intestinal immune system modulating activities (1.41 and 1.52 fold of saline control, respectively) compared to hot-water extracts of non-fermented mulberry leaves (MA-HW) and H. erinaceum mycelium (HE-HW) at $100\;{\mu}g$/mL. Meanwhile, when we tested the inhibitory effects of extracts on nitric oxide (NO), tumor necrosis factor (TNF)-${\alpha}$, and interleukin (IL)-$1{\beta}$ and IL-6 production, MA-HE-E significantly inhibited these pro-inflammatory mediators in LPS-stimulated RAW 264.7 cells (45.1, 41.3, 70.2, and 55.7% inhibition of LPS control at $1,000\;{\mu}g$/mL). In addition, MA-HE-HW and MA-HE-E did not show any cytotoxicity on RAW 264.7 cells at $1,000\;{\mu}g$/mL whereas HE-E and MA-E indicated cytotoxicity (80.1 and 30.7% cell viability of saline control). These results suggest that mulberry leaves fermented with H. erinaceum by solid-state culture might have enhanced immunomodulatory and anti-inflammatory effects compared to non-fermented mulberry leaves, resulting in ingredients biotransformed for fermentation with H. erinaceum mycelium.