• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.1945-1952
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• 2015

Inflammatory bowel disease (IBD) is a disease strongly associated with colorectal cancer (CRC) as a well-known precancerous condition. Alterations in DNA methylation and mutation in K-ras are believed to play an early etiopathogenic role in CRC and may also an initiating event through deregulation of molecular signaling. Epigenetic silencing of APC and SFRP2 in the WNT signaling pathway may also be involved in IBD-CRC. The role of aberrant DNA methylation in precancerous state of colorectal cancer (CRC) is under intensive investigation worldwide. The aim of this study was to investigate the status of promoter methylation of MGMT-B, APC1A and SFRP2 genes, in inflamed and normal colon tissues of patients with IBD compared with control normal tissues. A total of 52 IBD tissues as well as corresponding normal tissues and 30 samples from healthy participants were obtained. We determined promoter methylation status of MGMT-B, SFRP2 and APC1A genes by chemical treatment with sodium bisulfite and subsequent MSP. The most frequently methylated locus was MGMT-B (71%; 34 of 48), followed by SFRP2 (66.6 %; 32 of 48), and APC1A (43.7%; 21 of 48). Our study demonstrated for the first time that hypermethylation of the MGMT-B and the SFRP2 gene promoter regions might be involved in IBD development. Methylation of MGMT-B and SFRP2 in IBD patients may provide a method for early detection of IBD-associated neoplasia.

• Molecular & Cellular Toxicology
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• v.3 no.4
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• pp.254-261
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• 2007

20-O-($\beta$-D-Glucopyranosyl)-20 (S)-protopanaxadiol (IH-901) is one of the major metabolites of ginsenosides from Panax ginseng, and is suggested that IH-901 has been associated with various pharmacological and physiological activities. In this study, we demonstrate that IH-901 induced anti-inflammation in HT-29 human colon adenocarcinoma cells. Our results showed that IH-901 inhibited cell proliferation of HT-29 in a time- and dose-dependent manner. We also found that IH-901 was significantly decreased expression of iNOS compared with non-treated. We observed effect of IH-901 related with inflammatory genes using by cDNA microarray. We were known that the 34 inflammatory genes such as E2F, CDK6, TNF-$\alpha$, and PKC were down-regulated. Thus, these results suggest that IH-901 may have a potential preventive factor to improving cancer induced by chronic inflammation.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.6
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• pp.1305-1313
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• 2009

Saengjihwangeum-ja (SJHEJ) was recorded in DongEuiBoGam as being able to be used for treatment of Sogal whose concept had been applied to Diabetes Mellitus (DM). Modification of proteins by long term circulation of glucose leads to the formation of advanced glycation end product(AGE). Recent immunological studies demonstrated that ligation of AGE play an important role in the development of diabetic complications including atherosclerosis, which includes activation, adhesion, and migration of monocytes. Also, AGE and Maillard reaction product(MRP) could augment monocyte inflammatory responses via ligation of AGE receptor. In this study, the effects of SJHEJ extracts on the expression of inflammatory response-related genes such as tumor necrosis factor-$\alpha$, monocyte chemoattractant protein-1, interferon-g-inducible protein-10, and cyclooxygenase-2 in the human monocyte cell line, THP-1 cells. Reverse transcriptase-polymerase chain reaction revealed that SJHEJ had inhibitory effects on the expression of the TNF-a, MCP-1, IP-10, COX2, IL-1b genes in MRP-induced THP-1 cells. Treatment with SJHEJ had reduced reactive oxygen production in THP-1 cells stimulated by MRP. These inhibitory effects might be exerted via prevention of oxidative stress in activated monocytes. In addition, radical scavenging activity of SJHEJ was increased. These results suggest that SJHEJ has a beneficial effects for improve diabetic vascular complication.

• BMB Reports
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• v.52 no.10
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• pp.613-618
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• 2019

Microglial cells are known as the main immune cells in the central nervous system, both regulating its immune response and maintaining its homeostasis. Furthermore, the antioxidant ${\alpha}-lipoic$ acid (LA) is a recognized therapeutic drug for diabetes because it can easily invade the blood-brain barrier. This study investigated the effect of ${\alpha}-LA$ on the inflammatory response in lipopolysaccharide (LPS)-treated BV-2 microglial cells. Our results revealed that ${\alpha}-LA$ significantly attenuated several inflammatory responses in BV-2 microglial cells, including pro-inflammatory cytokines, such as tumor necrosis $factor-{\alpha}$ and interleukin (IL)-6, and other cytotoxic molecules, such as nitric oxide and reactive oxygen species. In addition, ${\alpha}-LA$ inhibited the LPS-induced phosphorylation of ERK and p38 and its pharmacological properties were facilitated via the inhibition of the nuclear factor kappa B signaling pathway. Moreover, ${\alpha}-LA$ suppressed the activation of NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasomes, multiprotein complexes consisting of NLRP3 and caspase-1, which are involved in the innate immune response. Finally, ${\alpha}-LA$ decreased the genes accountable for the M1 phenotype, $IL-1{\beta}$ and ICAM1, whereas it increased the genes responsible for the M2 phenotype, MRC1 and ARG1. These findings suggest that ${\alpha}-LA$ alleviates the neuroinflammatory response by regulating microglial polarization.

• Tuberculosis and Respiratory Diseases
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• v.84 no.1
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• pp.55-66
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• 2021

Background: Particulate matter 10 (PM₁₀; airborne particles <10 ㎛) inhalation has been demonstrated to induce airway and lung diseases. In this study, we investigate the effects of PM₁₀ inhalation on RNA expression in lung tissues using a murine model. Methods: Female BALB/c mice were affected with PM₁₀, ovalbumin (OVA), or both OVA and PM₁₀. PM₁₀ was administered intranasally while OVA was both intraperitoneally injected and intranasally administered. Treatments occurred 4 times over a 2-week period. Two days after the final challenges, mice were sacrificed. Full RNA sequencing using lung homogenates was conducted. Results: While PM₁₀ did not induce cell proliferation in bronchoalveolar fluid or lead to airway hyper-responsiveness, it did cause airway inflammation and lung fibrosis. Levels of interleukin 1β, tumor necrosis factor-α, and transforming growth factor-β in lung homogenates were significantly elevated in the PM₁₀-treated group, compared to the control group. The PM₁₀ group also showed increased RNA expression of Rn45a, Snord22, Atp6v0c-ps2, Snora28, Snord15b, Snora70, and Mmp12. Generally, genes associated with RNA splicing, DNA repair, the inflammatory response, the immune response, cell death, and apoptotic processes were highly expressed in the PM₁₀-treated group. The OVA/PM₁₀ treatment did not produce greater effects than OVA alone. However, the OVA/PM₁₀-treated group did show increased RNA expression of Clca1, Snord22, Retnla, Prg2, Tff2, Atp6v0c-ps2, and Fcgbp when compared to the control groups. These genes are associated with RNA splicing, DNA repair, the inflammatory response, and the immune response. Conclusion: Inhalation of PM₁₀ extensively altered RNA expression while also inducing cellular inflammation, fibrosis, and increased inflammatory cytokines in this murine mouse model.

• Journal of Animal Science and Technology
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• v.64 no.6
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• pp.1144-1172
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• 2022

Salmonella enterica serovar Typhimurium isolate HJL777 is a virulent bacterial strain in pigs. The high rate of salmonella infection are at high risk of non-typhoidal salmonella gastroenteritis development. Salmonellosis is most common in young pigs. We investigated changes in gut microbiota and biological function in piglets infected with salmonella via analysis of rectal fecal metagenome and intestinal transcriptome using 16S rRNA and RNA sequencing. We identified a decrease in Bacteroides and increase in harmful bacteria such as Spirochaetes and Proteobacteria by microbial community analysis. We predicted that reduction of Bacteroides by salmonella infection causes proliferation of salmonella and harmful bacteria that can cause an intestinal inflammatory response. Functional profiling of microbial communities in piglets with salmonella infection showed increasing lipid metabolism associated with proliferation of harmful bacteria and inflammatory responses. Transcriptome analysis identified 31 differentially expressed genes. Using gene ontology and Innate Immune Database analysis, we identified that BGN, DCN, ZFPM2 and BPI genes were involved in extracellular and immune mechanisms, specifically salmonella adhesion to host cells and inflammatory responses during infection. We confirmed alterations in gut microbiota and biological function during salmonella infection in piglets. Our findings will help prevent disease and improve productivity in the swine industry.

• Korean Journal of Organic Agriculture
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• v.26 no.3
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• pp.501-514
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• 2018

Taraxacum hallaisanense (pr), a species of the family Compositae is a perennial herb plants that inhabit to Jeju Island. In the study, we performed to determine the anti-inflammatory effects in LPS-induced RAW 264.7 cells and antioxidant activity of ethanol extracts from T. hallaisanense whole plants. The antioxidant activity of extracts was measured by contents of polyphenol and flavonoid, DPPH radical scavenging, and reducing power activity. The anti-inflammatory effect of T. hallaisanense extracts was measured by NO and $IL-1{\beta}$ production inhibitory activity and the expression of pro-inflammatory in lipopolysaccharide (LPS)-induced Raw 264.7 cells. Also, the expression of pro-inflammatory genes such as iNOS, COX-2 and NF-kB protein were reduced. In the cytotoxicity measurement by cytotoxicity kit, the extract was exhibited Raw 264.7 cell viabilities as nontoxic result in concentration of $25{\sim}400{\mu}g/ml$. These results indicated that ethanol extracts of T. hallaisanense whole plants expected development possibility as nutrial additives through high anti-inflammatory effects and antioxidant activity.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.1
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• pp.91-99
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• 2016

(E)-3-(3-methoxyphenyl)-1-(2-pyrrolyl)-2-propenone (MPP) is an aldol condensation product resulting from pyrrole-2-carbaldehyde and m- and p- substituted acetophenones. However, its biological activity has not yet been evaluated. Since it has been reported that some propenone-type compounds display anti-inflammatory activity, we investigated whether MPP could negatively modulate inflammatory responses. To do this, we employed lipopolysaccharide (LPS)-stimulated macrophage-like RAW264.7 cells and examined the inhibitory levels of nitric oxide (NO) production and transcriptional activation, as well as the target proteins involved in the inflammatory signaling cascade. Interestingly, MPP was found to reduce the production of NO in LPS-treated RAW264.7 cells, without causing cytotoxicity. Moreover, this compound suppressed the mRNA levels of inflammatory genes, such as inducible NO synthase (iNOS) and tumor necrosis factor (TNF)-${\alpha}$. Using luciferase reporter gene assays performed in HEK293 cells and immunoblotting analysis with nuclear protein fractions, we determined that MPP reduced the transcriptional activation of nuclear factor (NF)-${\kappa}B$. Furthermore, the activation of a series of upstream signals for NF-${\kappa}B$ activation, composed of Src, Syk, Akt, and $I{\kappa}B{\alpha}$, were also blocked by this compound. It was confirmed that MPP was able to suppress autophosphorylation of overexpressed Src and Syk in HEK293 cells. Therefore, these results suggest that MPP can function as an anti-inflammatory drug with NF-${\kappa}B$ inhibitory properties via the suppression of Src and Syk.

• Biomolecules & Therapeutics
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• v.22 no.1
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• pp.10-16
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• 2014

Derivatives of caffeic acid have been reported to possess diverse pharmacological properties such as anti-inflammatory, anti-tumor, and neuroprotective effects. However, the biological activity of methyl p-hydroxycinnamate, an ester derivative of caffeic acid, has not been clearly demonstrated. This study aimed to elucidate the anti-inflammatory mechanism of methyl p-hydroxycinnamate in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Methyl p-hydroxycinnamate significantly inhibited LPS-induced excessive production of pro-inflammatory mediators such as nitric oxide (NO) and $PGE_2$ and the protein expression of iNOS and COX-2. Methyl p-hydroxycinnamate also suppressed LPS-induced overproduction of pro-inflammatory cytokines such as IL-$1{\beta}$ and TNF-${\alpha}$. In addition, methyl p-hydroxycinnamate significantly suppressed LPS-induced degradation of $I{\kappa}B$, which retains NF-${\kappa}B$ in the cytoplasm, consequently inhibiting the transcription of pro-inflammatory genes by NF-${\kappa}B$ in the nucleus. Methyl p-hydroxycinnamate exhibited significantly increased Akt phosphorylation in a concentration-dependent manner. Furthermore, inhibition of Akt signaling pathway with wortmaninn abolished methyl p-hydroxycinnamate-induced Akt phosphorylation. Taken together, the present study clearly demonstrates that methyl p-hydroxycinnamate exhibits anti-inflammatory activity through the activation of Akt signaling pathway in LPS-stimulated RAW264.7 macrophage cells.

• Biomedical Science Letters
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• v.26 no.2
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• pp.85-92
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• 2020

Various beneficial effects of sweet persimmon (Diospyros kaki T.) including anti-oxidation, anti-bacteria and viruses, anti-allergy were widely reported previously. However, the anti-inflammatory effect and its molecular mechanisms are not clear. In this study, the anti-inflammatory effect of the extracts of flower bud and fruit of sweet persimmon was investigated in LPS-treated RAW264.7 cells. Both extracts of flower bud and fruit showed strong inhibitory effect on the LPS-induced NF-κB activation. IκBα, the inhibitor of NF-κB, was increased and the expressions of NF-κB target genes, COX-2 and iNOS, were suppressed by the treatment with the extracts of flower bud and fruit. The expressions of pro-inflammatory cytokines, IL-1β, IL-6, TNF-α were also suppressed by the extracts. In addition, the LPS-induced wnt/β-catenin pathway and its related gene expressions including cyclin D1, wnt 3a, wnt 5a were suppressed by the extracts. The extracts also showed anti-oxidant activity and suppressive effect on the LPS-induced apoptosis of RAW264.7 cells. These results suggest that the flower bud and fruit of sweet persimmon display strong anti-inflammatory effect through inhibiting the pro-inflammatory signaling pathways in the cells.