• Korean Journal of Food Science and Technology
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• v.44 no.3
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• pp.331-336
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• 2012

In this study, we selected Gardeniae fructus (GF) as an anti-inflammatory functional material and improved the biological activity of GF through the treatment of ${\beta}$-glucosidase. For the simple evaluation of anti-inflammatory activity, the inhibitory activity of GF extract (GFE) on the production of NO by RAW264.7 cells in the presence of LPS was examined. ${\beta}$-glucosidase originating from Aspergillus niger or Aspergillus fumigatus has effectively improved the anti-inflammatory activity of GFE. The enzyme treatment raised the activity of GFE by more than 10 times. The optimum conditions for the enzyme reaction were at pH 4.6, $45^{\circ}C$, and 20 U/mL for 24 h with agitation. In addition, in vitro production of cytokines (IL-$1{\beta}$, IL-6, TNF-${\alpha}$), COX-2, and the NF-${\kappa}B$ activation of RAW264.7 cells decreased more in the presence of GFE treated with ${\beta}$-glucosidase originating from Aspergillus niger (GFAN) than in the presence of GFE. These results suggest that enzyme-treated GFE might be a potential candidate for natural anti-inflammatory food materials.

• Biomolecules & Therapeutics
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• v.29 no.3
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• pp.331-341
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• 2021

Liver cancer is a common tumor and currently the second leading cause of cancer-related mortality globally. Liver cancer is highly related to inflammation as more than 90% of liver cancer arises in the context of hepatic inflammation, such as hepatitis B virus and hepatitis C virus infection. Despite significant improvements in the therapeutic modalities for liver cancer, patient prognosis is not satisfactory due to the limited efficacy of current drug therapies in anti-metastatic activity. Therefore, developing new effective anti-cancer agents with anti-metastatic activity is important for the treatment of liver cancer. In this study, SP-8356, a verbenone derivative with anti-inflammatory activity, was investigated for its effect on the growth and migration of liver cancer cells. Our findings demonstrated that SP-8356 inhibits the proliferation of liver cancer cells by inducing apoptosis and suppressing the mobility and invasion ability of liver cancer cells. Functional studies revealed that SP-8356 inhibits the mitogen-activated protein kinase and nuclear factor-kappa B signaling pathways, which are related to cell proliferation and metastasis, resulting in the downregulation of metastasis-related genes. Moreover, using an orthotopic liver cancer model, tumor growth was significantly decreased following treatment with SP-8356. Thus, this study suggests that SP-8356 may be a potential agent for the treatment of liver cancer with multimodal regulation.

• Toxicological Research
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• v.22 no.3
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• pp.293-299
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• 2006

We demonstrate that magnolol, a hydroxylated biphenyl compound isolated from Magnolia officinalis, inhibits LPS-induced expression of iNOS gene in RAW 264.7 cells(murine macrophage cell line). Treatment of RAW 264.7 cells with magnolol inhibited LPS-stimulated nitric oxide production in a dose-related manner. RT-PCR analysis showed that the decrease of NO was due to the inhibition of iNOS gene expression. Western immunoblot analysis of phosphorylate p38 kinase showed magnolol significantly inhibited the phosphorylation of p38 kinase which is important in the regulation of iNOS gene expression. The specific p38 inhibiter SB203580 abrogated the LPS-induced NO generation and iNOS expression, whereas the selective MEK-1 inhibitor PD98059 did not affect the NO induction. Immunostaining of p65 and reporter gene assay showed that magnolol inhibited NF-${\kappa}/Rel$ nuclear translocation and transcriptional activation, respectively. Collectively, this series of experiments indicates that magnolol inhibits iNOS gene expression by blocking NF-k/Rel and p38 kinase signaling. Due to the critical role that NO release plays in mediating inflammatory responses, the inhibitory effects of magnolol or iNOS suggest that magnolol may represent a useful anti-inflammatory agent.

• Kidney Research and Clinical Practice
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• v.36 no.2
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• pp.145-157
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• 2017

Background: Vitamin D is considered to exert a protective effect on various renal diseases but its underlying molecular mechanism remains poorly understood. This study aimed to determine whether paricalcitol attenuates inflammation and apoptosis during lipopolysaccharide (LPS)-induced renal proximal tubular cell injury through the prostaglandin $E_2$ ($PGE_2$) receptor EP4. Methods: Human renal tubular epithelial (HK-2) cells were pretreated with paricalcitol (2 ng/mL) for 1 hour and exposed to LPS ($1{\mu}g/mL$). The effects of paricalcitol pretreatment in relation to an EP4 blockade using AH-23848 or EP4 small interfering RNA (siRNA) were investigated. Results: The expression of cyclooxygenase-2, $PGE_2$, and EP4 were significantly increased in LPS-exposed HK-2 cells treated with paricalcitol compared with cells exposed to LPS only. Paricalcitol prevented cell death induced by LPS exposure, and the cotreatment of AH-23848 or EP4 siRNA offset these cell-protective effects. The phosphorylation and nuclear translocation of p65 nuclear factor-kappaB ($NF-{\kappa}B$) were decreased and the phosphorylation of Akt was increased in LPS-exposed cells with paricalcitol treatment. AH-23848 or EP4 siRNA inhibited the suppressive effects of paricalcitol on p65 $NF-{\kappa}B$ nuclear translocation and the activation of Akt. The production of proinflammatory cytokines and the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells were attenuated by paricalcitol in LPS exposed HK-2 cells. The cotreatment with an EP4 antagonist abolished these anti-inflammatory and antiapoptotic effects. Conclusion: EP4 plays a pivotal role in anti-inflammatory and antiapoptotic effects through Akt and $NF-{\kappa}B$ signaling after paricalcitol pretreatment in LPS-induced renal proximal tubule cell injury.

• BMB Reports
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• v.55 no.3
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• pp.136-141
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• 2022

Inflammation is one of the body's natural responses to injury and illness as part of the healing process. However, persistent inflammation can lead to chronic inflammatory diseases and multi-organ failure. Altered mitochondrial function has been implicated in several acute and chronic inflammatory diseases by inducing an abnormal inflammatory response. Therefore, treating inflammatory diseases by recovering mitochondrial function may be a potential therapeutic approach. Recently, mitochondrial transplantation has been proven to be beneficial in hyperinflammatory animal models. However, it is unclear how mitochondrial transplantation attenuates inflammatory responses induced by external stimuli. Here, we isolated mitochondria from umbilical cord-derived mesenchymal stem cells, referred as to PN-101. We found that PN-101 could significantly reduce LPS-induced mortality in mice. In addition, in phorbol 12-myristate 13-acetate (PMA)-treated THP-1 macrophages, PN-101 attenuated LPS-induced increase production of pro-inflammatory cytokines. Furthermore, the anti-inflammatory effect of PN-101 was mediated by blockade of phosphorylation, nuclear translocation, and trans-activity of NFκB. Taken together, our results demonstrate that PN-101 has therapeutic potential to attenuate pathological inflammatory responses.

• Biomedical Science Letters
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• v.23 no.2
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• pp.104-110
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• 2017

Inflammation is a pathophysiological process that is known to be involved in numerous diseases. Microbial infection or tissue injury activates inflammatory responses, resulting in the induction of proinflammatory proteins including inducible nitric oxide synthase (iNOS). Aster yomena is used in traditional Korean remedies. Here, we investigated the effects of ethanol extracts of Aster yomena (EAY) on the expression of iNOS induced by ovalbumin (OVA), one of the major egg allergens, or lipopolysaccharide (LPS), a Toll-like receptor 4 agonist. EAY inhibited OVA- or LPS-induced $NF-{\kappa}B$ activation. EAY also suppressed OVA- or LPS-induced iNOS expression and nitrite production. These results suggest that EAY has the specific mechanism for anti-inflammatory responses and the potential to be developed as a potent anti-inflammatory and anti-allergic drug.

• Journal of Applied Biological Chemistry
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• v.57 no.3
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• pp.227-234
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• 2014

The anti-inflammatory effect of Sargassum micracanthum water extract (SMWE) was investigated using lipopolysaccharide (LPS)-induced inflammatory response in this study. The murine macrophage cell line RAW 264.7 cells were used and MTT assay was performed to measure the cell proliferation ability. The secretion of nitric oxide (NO), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-6 (IL-6), and IL-$1{\beta}$ was measured in LPS-induced RAW 264.7 cells by ELISA. The expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and nuclear transcription factor-kappa B p65 protein was studied by immunoblotting. The Balb/c mice were used for an acute toxicity test, and imprinting control region mice were purchased to evaluate a croton oil-induced ear edema. As a result, there was no cytotoxicity in the macrophage proliferation treated with SMWE compared to the control. NO levels decreased with increasing concentration of SMWE and were inhibited over 50%. Moreover, the secretion of IL-6, TNF-${\alpha}$, and IL-$1{\beta}$ was suppressed in a dose-dependent manner, especially, IL-$1{\beta}$ inhibition activity was over 50% at 50 ${mu}g$/mL. The formation of ear edema of mice was reduced at the highest dose tested compared to that in the control. Moreover, in acute toxicity test, no moralities occurred in mice administered 5,000 mg/kg body weight of SMWE over 2 weeks observation period. These results suggested that SMWE may have significant effects on inflammatory factors and be potential anti-inflammatory therapeutic materials.

• International Journal of Internet, Broadcasting and Communication
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• v.12 no.2
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• pp.98-112
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• 2020

There is a strong connection between the diet rich in antioxidants and the decreased incidence of inflammatory bowel disease and cancerous diseases. Diets that are rich in anti-oxidants particularly include fruits and vegetables containing the high amounts of vitamin A-E, carotenoids, and minerals. The supercritical heat-treated radish extracts of the research result had an inhibitory effect on the development of aberrant crypt foci (ACF), namely, preneoplastic lesions having a potential to become cancer cells and reduced the number of the aberrant crypt foci (ACF) consisting of four or more aberrant crypts (AC) having high risk to become tumors by about half. The supercritical heat-treated radish extracts can reduce the incidence of preneoplastic lesions having a high risk of developing cancer by about 28 %. DSS-treated mice developed symptoms similar to those of human UC, such as severe bloody diarrhea and weight loss. Supercritical heat-treated radish extracts, as well as sulfasalazine, suppressed colonic length and mucosal inflammatory infiltration. In addition, supercritical heat-treated radish extracts treatment significantly reduced the expression of pro-inflammatory signaling molecules through suppression both mitogen-activated protein kinases (MAPK) and nuclear factor-kappa B (NF-kB) signaling pathways, and prevented the apoptosis of colon. Moreover, supercritical heat-treated radish extracts administration significantly led to the up-regulation of anti-oxidant enzyme including SOD and Catalase.

• Journal of Microbiology and Biotechnology
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• v.30 no.12
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• pp.1927-1936
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• 2020

Tunicates are known to contain biologically active materials and one species in particular, the sea peach (Halocynthia aurantium), has not been thoroughly studied. In this study we aimed to analyze the fatty acids profile of the H. aurantium body wall and its immunomodulatory effects on RAW264.7 macrophage-like cells. The fatty acids were classified into three categories: saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs). Omega-3 fatty acid content, including EPA and DHA, was higher than omega-6 fatty acids. H. aurantium body wall fatty acids exhibited enhanced immune response and anti-inflammatory effects on RAW264.7 macrophage-like cells. Under normal conditions, fatty acids significantly increase nitric oxide (NO) and PGE2 production in a dose-dependent manner, thereby improving the immune response. On the other hand, in LPS-treated RAW264.7 cells, fatty acids significantly decreased nitric oxide (NO) and PGE2 production in a dose-dependent manner, thereby enhancing anti-inflammatory effects. Fatty acids transcriptionally control the expression of the immune-associated genes, iNOS, IL-1β, IL-6, COX-2, and TNF-α, via the MAPK and NF-κB signaling cascades in RAW264.7 cells. However, in LPS-stimulated RAW264.7 cells, H. aurantium body wall fatty acids significantly inhibited expression of inflammatory cytokine; similarly, production of COX-2 and PGE2 was inhibited. The results of our present study provide insight into the immune-improving and anti-inflammatory effects of H. aurantium body wall fatty acids on macrophages. In addition, our study demonstrates that H. aurantium body wall is a potential source of immune regulatory components.

• Journal of Dental Anesthesia and Pain Medicine
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• v.19 no.5
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• pp.253-260
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• 2019

Background: Sometimes general anesthesia is required for dental surgery in pregnant women. Facial bone fractures or neck abscess should be treated immediately. Dental surgery, however, creates a stressful situation that can cause inflammation. Inflammatory responses are a well-known major cause of preterm labor and preterm birth. Here we demonstrate the effects of remifentanil on the factors related to preterm labor and its mechanism of action on amniotic-derived epithelial cells (WISH cells). Methods: WISH cells were exposed to lipopolysaccharide (LPS) for 24 h and co-treated with various concentrations of remifentanil. MTT assays were performed to measure cell viability. To explain the effects of remifentanil on the factors related to inflammation in WISH cells, activation of nuclear factor kappa B ($NF-{\kappa}B$) and p38 and the expression of interleukin $(IL)-1{\beta}$, tumor necrosis factor $(TNF)-{\alpha}$, cyclooxygenase (COX)2, and prostaglandin E $(PGE)_2$ were quantified using western blotting and RT-PCR, respectively. Results: Remifentanil did not affect WISH cell viability. In western blot analysis, co-treatment with remifentanil resulted in decreased phosphorylation of $NF-{\kappa}B$, and expression of COX2 and $PGE_2$ in LPS-induced inflammation, but the results were statistically significant only at low concentrations. Reduction of $IL-1{\beta}$ and $TNF-{\alpha}$ expression was also observed with RT-PCR. Conclusion: Co-treatment with remifentanil does not affect the viability of WISH cells, but reduces the expression of the factors related to inflammation, which can induce uterine contraction and preterm labor. These findings provide evidence that remifentanil may inhibit uterine contraction and preterm labor in clinical settings.