• Journal of Applied Biological Chemistry
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• v.64 no.3
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• pp.263-268
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• 2021

7-Hydroxy-4-methylcoumarin (7H-4MC) inhibits hyaluronan production in multiple cell lines and tissue types both in vitro and in vivo. It is a commercially available drug approved for human use, called hymecromone, in European and Asian countries to prevent biliary spasms. Nevertheless, as the pharmacological efficacy of 7H-4MC has not yet been reported in macrophages, this study investigated its anti-inflammatory effects and mechanism of action using lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. LPS-induced RAW 264.7 cells were treated with various concentrations of 7H-4MC (62.5, 125, 250, and 500 μM). The application of 7H-4MC significantly reduced nitric oxide and prostaglandin E₂ production without cytotoxic effects. Additionally, 7H-4MC strongly decreased the expression of inducible nitric oxide synthase and cyclooxygenase. Furthermore, 7H-4MC reduced the production of proinflammatory cytokines, such as tumor necrosis factor-α, interleukin (IL)-1β, and IL-6. Finally, 7H-4MC exerted its potent anti-inflammatory actions via the upregulation of IκB-α production, which led to the inhibition of nuclear factor-κB (NF-κB) activity. These results, obtained in macrophage cell lines, suggest that 7H-4MC prevents inflammatory diseases via the NF-κB signaling pathway and that its use could be beneficial for human health. Ultimately, this is the first report describing the anti-inflammatory activity of 7H-4MC in a macrophage cell line.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.8
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• pp.1158-1165
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• 2014

This study investigated the anti-inflammatory effects of Sargassum fulvellum ethanol extract (SFEE) on the lipopolysaccharide (LPS)-induced inflammatory response. SFEE remarkably suppressed production of NO and pro-inflammatory cytokines (IL-6, $TNF-{\alpha}$, and $IL-1{\beta}$ at 50 and $100{\mu}g/mL$. There were no cytotoxic effects on proliferation of macrophages treated with SFEE compared to the control. SFEE reduced expression of iNOS and COX-2 proteins in a dose-dependent manner. The formation of edema in mouse ears was reduced at the highest dose tested compared to the control. Moreover, in the acute toxicity test, no mortality occurred in mice administered 5,000 mg/kg body weight of SFEE over the 2-week observation period. These results suggest that SFEE may have significant effects on inflammatory factors and be a potential anti-inflammatory therapeutic material.

• Journal of Ginseng Research
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• v.42 no.2
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• pp.218-224
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• 2018

Background: Compound K (CK) is a ginsenoside, a metabolite of Panax ginseng. There is interest both in increasing skin health and antiaging using natural skin care products. In this study, we explored the possibility of using CK as a cosmetic ingredient. Methods: To assess the antiaging effect of CK, RT-PCR was performed, and expression levels of matrix metalloproteinase-1, cyclooxygenase-2, and type I collagen were measured under UVB irradiation conditions. The skin hydrating effect of CK was tested by RT-PCR, and its regulation was explored through immunoblotting. Melanin content, melanin secretion, and tyrosinase activity assays were performed. Results: CK treatment reduced the production of matrix metalloproteinase-1 and cyclooxygenase-2 in UVB irradiated NIH3T3 cells and recovered type I collagen expression level. Expression of skin hydrating factors-filaggrin, transglutaminase, and hyaluronic acid synthases-1 and -2-were augmented by CK and were modulated through the inhibitor of ${\kappa}B{\alpha}$, c-Jun N-terminal kinase, or extracellular signal-regulated kinases pathway. In the melanogenic response, CK did not regulate tyrosinase activity and melanin secretion, but increased melanin content in B16F10 cells was observed. Conclusion: Our data showed that CK has antiaging and hydrating effects. We suggest that CK could be used in cosmetic products to protect the skin from UVB rays and increase skin moisture level.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.6
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• pp.1320-1331
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• 2009

Oxidative stress and inflammation are important events in the development of chronic inflammatory diseases including arthritis, atherosclerosis, diabetes, hypertension. Cynomorium songaricum (CS) has been used as a traditional Korean herbal medicine, and it is currently used in traditional clinics to treat frequent urination, spermatorrhea, weakness of the sinews and constipation in the folk medicine. The aim of this study was to determine whether fractionated extracts of CS inhibit free radical generation such as DPPH radical, superoxide radical, nitric oxide and peroxynitrite, production of nitrite an index of NO, $PGE_2$, iNOS, COX-2 and pro-inflammatory cytokines in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. Cytotoxic activity of extracts on RAW 264.7 cells was measured using 5-(3-caroboxymeth-oxyphenyl)-2H-tetra-zolium inner salt (MTS) assay. Our results indicated that the most superior extract which scavenged DPPH radical, reactive oxygen species (ROS) and RNS was CS ethyl acetate extract (CSEA). Moreover, CSEA significantly inhibited the LPS-induced NO, $PGE_2$ production and iNOS, COX-2 expression accompanied by an attenuation of TNF-$\alpha$, IL-$1{\beta}$ and IL-6 formation in macrophages. Furthermore, CSEA treatment also blocked LPS-induced intracellular ROS production and the activation of NF-${\kappa}B$. These findings indicate that CSEA inhibits the production of pro-inflammatory mediators and cytokines via the suppression of ROS production and NF-${\kappa}B$ activation. Take together, these results indicate that CSEA has the potential for use as an natural anti-oxidant and an agent of anti-chronic inflammatory diseases.

• Journal of Microbiology and Biotechnology
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• v.27 no.9
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• pp.1628-1638
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• 2017

Viola tianshanica Maxim, belonging to the Violaceae plant family, is traditionally used in Uighur medicine for treating pneumonia, headache, and fever. There is, however, a lack of basic understanding of its pharmacological activities. This study was designed to observe the effects of the ethanol extract (TSM) from Viola tianshanica Maxim on the inflammation response in acute lung injury (ALI) induced by LPS and the possible underlying mechanisms. We found that TSM (200 and 500 mg/kg) significantly decreased inflammatory cytokine production and the number of inflammatory cells, including macrophages and neutrophils, in bronchoalveolar lavage fluid. TSM also markedly inhibited the lung wet-to-dry ratio and alleviated pathological changes in lung tissues. In vitro, after TSM ($12.5-100{\mu}g/ml$) treatment to RAW 264.7 cells for 1 h, LPS ($1{\mu}g/ml$) was added and the cells were further incubated for 24 h. TSM dose-dependently inhibited the levels of proinflammatory cytokines, such as NO, $PGE_2$, $TNF-{\alpha}$, IL-6, and $IL-1{\beta}$, and remarkably decreased the protein and mRNA expression of $TNF-{\alpha}$ and IL-6 in LPS-stimulated RAW 264.7 cells. TSM also suppressed protein expression of $p-I{\kappa}Ba$ and p-ERK1/2 and blocked nuclear translocation of $NF-{\kappa}B$ p65. The results indicate that TSM exerts anti-inflammatory effects related with inhibition on $NF-{\kappa}B$ and MAPK (p-ERK1/2) signaling pathways. In conclusion, our data demonstrate that TSM might be a potential agent for the treatment of ALI.

• BMB Reports
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• v.48 no.9
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• pp.495-500
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• 2015

Up-regulation of cell adhesion molecules and proinflammatory cytokines contributes to enhanced monocyte adhesiveness and infiltration into the skin, during the pathogenesis of various inflammatory skin diseases, including atopic dermatitis. In this study, we examined the anti-inflammatory effects of butein, a tetrahydroxychalcone, and its action mechanisms using TNF-α-stimulated keratinocytes. Butein significantly inhibited TNF-α-induced ICAM-I expression and monocyte adhesion in human keratinocyte cell line HaCaT. Butein also decreased TNF-α-induced pro-inflammatory mediators, such as IL-6, IP-10 and MCP-1, in HaCaT cells. Butein decreased TNF-α-induced ROS generation in a dose-dependent manner in HaCaT cells. In addition, treatment of HaCaT cells with butein suppressed TNF-α-induced MAPK activation. Furthermore, butein suppressed TNF-α-induced NF-kappaB activation. Overall, our results indicate that butein has immunomodulatory activities by inhibiting expression of proinflammatory mediators in keratinocytes. Therefore, butein may be used as a therapeutic agent for the treatment of inflammatory skin diseases. [BMB Reports 2015; 48(9): 495-500]

• Korean Journal of Organic Agriculture
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• v.26 no.4
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• pp.661-676
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• 2018

Veronica persica (V. persica) is a perennial plant that is broadly distributed in Europe, Asia and so on. V. persica is used for pain about the lower abdomen and low back. The aim of this study was to investigate the anti-oxidant and anti-inflammatory effects of V. persica ethanol extract in LPS-induced RAW 264.7 cells. To evaluate the anti-oxidant activity, the DPPH and ABTS radical scavenging, total polyphenol and flavonoid contents, and reducing power activity were carried out. The DPPH and ABTS radical scavenging activity were evaluated as 72.0% and 73.0% at the concentrations of 200 and $500{\mu}g/mL$, respectively. Total polyphenol and flavonoid contents of V. persica extracts were measured as 65.22 mg/g and 43.82 mg/g at the concentration of 1 mg/mL. The reducing power activity measurement showed 53.0% activity at 1 mg/mL. The anti-inflammatory effects of the V. persica extract were evaluated in LPS induced RAW 264.7 cells. In the evaluation of cell viability by proliferation ＆ cytotoxicity assay kit, the cytotoxicity of the extract was not confirmed at $0{\sim}800{\mu}g/mL$ concentration. And the V. persica significantly inhibited NO production in a concentration dependent manner. The inhibition effects of NO in cell medium of V. persica was over 80% at $800{\mu}g/mL$. The V. persica also suppressed the expression of iNOS, COX-2, and phosphorylation of $NF-{\kappa}B$ and $IkB-{\alpha}$ proteins. These results indicate that the V. persica has anti-oxidant and anti-inflammatory effects by modulating $NF-{\kappa}B$ signaling pathways and can be used as natural functional materials.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.1
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• pp.15-23
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• 2016

Acetaminophen (APAP) overdose is one of the most common causes of acute liver failure. The study aimed to investigate the protective effect of carnosic acid (CA) on APAP-induced acute hepatotoxicity and its underlying mechanism in mice. To induce hepatotoxicity, APAP solution (400 mg/kg) was administered into mice by intraperitoneal injection. Histological analysis revealed that CA treatment significantly ameliorated APAP-induced hepatic necrosis. The levels of both alanine aminotransferase (ALT) and aspartate transaminase (AST) in serum were reduced by CA treatment. Moreover, CA treatment significantly inhibited APAP-induced hepatocytes necrosis and lactate dehydrogenase (LDH) releasing. Western blot analysis showed that CA abrogated APAP-induced cleaved caspase-3, Bax and phosphorylated JNK protein expression. Further results showed that CA treatment markedly inhibited APAP-induced pro-inflammatory cytokines TNF-${\alpha}$, IL-$1{\beta}$, IL-6 and MCP-1 mRNA expression and the levels of phosphorylated $I{\kappa}B{\alpha}$ and p65 protein in the liver. In addition, CA treatment reduced APAP- induced hepatic malondialdehyde (MDA) contents and reactive oxygen species (ROS) accumulation. Conversely, hepatic glutathione (GSH) level was increased by administration of CA in APAP-treated mice. Mechanistically, CA facilitated Nrf2 translocation into nuclear through blocking the interaction between Nrf2 and Keap1, which, in turn, upregulated anti-oxidant genes mRNA expression. Taken together, our results indicate that CA facilitates Nrf2 nuclear translocation, causing induction of Nrf2-dependent genes, which contributes to protection from acetaminophen hepatotoxicity.

• The Korea Journal of Herbology
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• v.30 no.5
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• pp.59-65
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• 2015

Objectives : Fermentation of herbs has been known to be helpful in improving the immune systems and protecting body against disease. The present study was conducted to evaluate anti-inflammatory effects of the fermentation extracts (FE) consisting of soybean, red ginseng andCitrus UnshiuPeel in lipopolysaccharide (LPS)-activated Raw264.7 cells.Methods : FE were prepared by the fermentation withBacillus Subtilisand then by extraction with ethanol (95%; prepared by the fermentation process). Cell viability was measured by MTT assay. Nitric oxide (NO) production was measured in culture media by Griess assay. The expression of nuclear factor (NF)-κB and inhibitory kappa B alpha (IκBα) was determined by Western blot.Results : LPS-induced production of NO and PGE₂was dose-dependently decreased by the treatment of FE in Raw264.7 cells. These suppressive effects of FE on NO and PGE₂production were related to the inhibition of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. FE inhibited LPS-induced production of pro-inflammatory cytokines, TNF-α, IL-6, and IL-1βin a dose-dependent manner. Furthermore, FE inhibited the NF-κB signaling pathway through the prevention of LPS-induced degradation of IκBαin cytosol and the nuclear translocation of NF-κB.Conclusions : These findings suggest that FE could have anti-inflammatory effects on LPS-induced inflammatory responses in macrophages.

• Journal of Physiology & Pathology in Korean Medicine
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• v.19 no.5
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• pp.1399-1404
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• 2005

In oriental medicine, Cheongpyehwadam-tang (CHT) has long been used for the cure of inflammatory diseases in the lung and bronchus such as bronchitis, bronchial asthma, pneumonia and tuberculosis. It's use is currently further extended for the treatment of allergic asthma. To investigate the anti-inflammatory effects of CHT, we investigated the effects of CHT on the lipopolysaccharide (LPS)-induced nitric oxide (NO) and pro-inflammatory cytokines ($TNF-{\alpha}$, IL-6, and $IL-1{\beta}$) production, and on the level of inducible nitric oxide synthase (iNOS) and proinflammatory cytokines expression in murine macrophage RAW 264.7 cells. CHT alone did not affect NO or pro-inflammatory cytokines production. In contrast, CHT inhibited LPS-induced NO and proinflammatory cytokines and the levels of LPS-induced iNOS and proinflarnmatory cytokine mRNA in a dose-dependent manner. CHT also inhibited the nuclear factor-kappa B (NF-kB) activation. Taken together, these results suggested that CHT inhibits the production of NO and pro-inflammatory cytokines in RAW 264.7 cells through blockade of NF-kB activation.