• Journal of Applied Biological Chemistry
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• v.63 no.2
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• pp.117-123
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• 2020

We examined the anti-inflammatory effect of the peel extract of the newly bred Korean apple (Malus domestica Borkh.) cultivar Green ball. To test its possible use as anti-inflammatory functional material, Raw 264.7 macrophages were treated with pro-inflammatory lipopolysaccharide (LPS) in the presence or absence of Green ball apple peel ethanol extract (GBE). Notably, up to 500 ㎍/mL of GBE did not result in any signs of inhibition on cellular metabolic activity or cytotoxicity in Raw 264.7 macrophages. Supplementation with GBE to LPS-treated Raw 264.7 macrophage significantly suppressed various pro-inflammatory responses in a dose-dependent manner, including i) nitric oxide (NO) production, ii) accumulation of inducible NO synthase and cyclooxygenase-2, iii) phosphorylation of nuclear factor-kappa B (NF-κB) subunit p65, and iv) expression of pro-inflammatory biomarker genes, including tumor necrosis factor alpha, interleukin 1 beta, interleukin 6, monocyte chemoattractant protein-1, and prostaglandin E synthase 2.

• Journal of Life Science
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• v.20 no.9
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• pp.1332-1338
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• 2010

To elucidate the mechanism underlying the regulation of hST8Sia I gene expression in FenR-induced SH-SY5Y cells, we characterized the promoter region of the hST8Sia I gene. Functional analysis of the 5'-flanking region of the hST8Sia I gene showed that the -1146 to -646 region functions as the FenR-inducible promoter of hST8Sia I in SH-SY5Y cells. Site-directed mutagenesis indicated that the NF-&B binding site at -731 to -722 was crucial for the FenR-induced expression of hST8Sia I in SH-SY5Y cells. To investigate which signal transduction pathway was involved in FenR-stimulated induction of hST8Sia I in SH-SY5Y cells, we performed Western blot analysis using phospho-specific antibodies in order to measure their degree of regulatory phosphorylation. Phosphorylations of AKT and RelA (p65) subunit of NF-${\kappa}B$ were significantly elevated in cytosolic and nuclear fractions of FenR-stimulated SH-SY5Y cells, respectively, than in control or DMSO-treated SH-SY5Y cells. These results suggest that FenR induce transcriptional up-regulation of hST8Sia I gene expression through translocation of RelA (p65) subunit of NF-${\kappa}B$ to nucleus by AKT signal pathway in SH-SY5Y cells.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2018.04a
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• pp.13-13
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• 2018

The anti-inflammatory (INF) compounds (1-15) were isolated from Agrimonia pilosa Ledeb. (APL) by activity-guided isolation technique. The isolated compounds (1-15) were identified as quercetin-7-O-rhanmoside (1), apigenin-7-O-glycoside (2), kaempferol-7-O-glycoside (3), apigenin-7-O-[6"-(butyl)-glycoside] (4), querceitn (5), kaempferol (6), apigenin (7), apigenin-7-O-[6"-(pentyl)-glycoside] (8), agrimonolide (9), agrimonolide-6-O-glucoside (10), desmethylagrimonolide (11), desmethylagrimonolide-6-O-glucoside (12), luteolin (13), vitexin (14) and isovitexin (15). Flavonoids, compound 2, 3, 11, and 14-15 have been found in APL for the first time. Furthermore, two novel flavone derivatives, compound 4 and 8, have been isolated inceptively in plant. In the no cytotoxicity concentration ranges of $0-20{\mu}M$, nitric oxide (NO) production level of 1-15 was estimated in LPS-treated Raw 264.7 macrophage cells. The flavone aglycones, 7 (apigenin, $IC_{50}=3.69{\pm}0.34{\mu}M$), 13 (luteolin, $IC_{50}=4.62{\pm}0.43{\mu}M$), 6 (kaempferol, $IC_{50}=14.43{\pm}0.23{\mu}M$) and 5 (quercetin, $IC_{50}=19.50{\pm}1.71{\mu}M$), exhibited excellent NO inhibitory (NOI) activity in dose-dependent manner. In the structure activity relationship (SAR) study of apigenin-derivatives (APD), apigenin; Api, apigenin-7-O-glucoside; Api-G, apignenin-7-O-[6"-(butyl)-glycoside]; Api-BG and apignenin-7-O-[6"-(pentyl)-glycoside]; Api-P, from APL on INF activity was investigated. The INF mediators level such as NO, INF-cytokines, NF-KB proteins, iNOS and COX-2 were sharply increased in Raw 264.7 cells by LPS. When pretreatment with APD in INF induced macrophages, NOI activity of Api was most effective than other APD with $IC_{50}$ values of $3.69{\pm}0.77{\mu}M$. And the NOI activity was declined in the following order: Api-BG ($IC_{50}=8.91{\pm}1.18{\mu}M$), Api-PG ($IC_{50}=13.52{\pm}0.85{\mu}M$) and API-G ($IC_{50}=17.30{\pm}0.66{\mu}M$). The NOI activity of two novel compounds, Api-PG and Api-BG were lower than their aglycone; Api, but more effective than Api-G (NOI: Api-PG and Api-BG). And their suppression ability on INF cytokines such as $TNF-{\alpha}$, $IL-1{\beta}$ and IL-6 mRNA showed the similar tendency. Therefore, the anti-INF mechanism study of Api-PG and Api-BG on nuclear factor-kappa B ($NF-{\kappa}B$) pathway, representative INF mechanism, was investigated and Api was used as positive control. Api-BF was more effectively prevent the than phosphorylation of $pI{\kappa}B$ kinase (p-IKK) and p65 than Api-PG in Raw 264.7 cells. In contrast, Api-PG and Api-BG were not reduced the phosphorylation of inhibitor of kappa B alpha ($I{\kappa}B{\alpha}$). Moreover, pretreatment with Api-PG and Api-BG, dose-dependently inhibited LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNAs and proteins in macrophage cells, and their expression were correlated with their NOI activity. Therefore, APL can be utilized to health promote agent associated with their AIN metabolites.

• Journal of Ginseng Research
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• v.45 no.5
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• pp.575-582
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• 2021

Background: In ginseng, there exists a glycolipoprotein complex with a special form of lipid LPAs called Gintonin. The purpose of this study is to show that Gintonin has a therapeutic effect on rheumatoid arthritis through LPA2 receptors. Methods: Fibroblast-like synoviocytes (FLS) were treated with Gintonin and stimulated with interleukin (IL)-1β. The antioxidant effect of Gintonin was measured using MitoSOX and H₂DCFDA experiments. The anti-arthritic efficacy of Gintonin was examined by analyzing the expression levels of inflammatory mediators, phosphorylation of mitogen-activated protein kinase (MAPK) pathways, and translocation of nuclear factor kappa B (NF-κB)/p65 into the nucleus through western blot. Next, after treatment with LPAR2 antagonist, western blot analysis was performed to measure inflammatory mediator expression levels, and NF-κB signaling pathway. Carrageenan/kaolin-induced arthritis rat model was used. Rats were orally administered with Gintonin (25, 50, and 100 mg/kg) every day for 6 days. The knee joint thickness, squeaking score, and weight distribution ratio (WDR) were measured as the behavioral parameters. After sacrifice, H&E staining was performed for histological analysis. Results: Gintonin significantly inhibited the expression of iNOS, TNF-α, IL-6 and COX-2. Gintonin prevented NF-κB/p65 from moving into the nucleus through the JNK and ERK MAPK phosphorylation in FLS cells. However, pretreatment with an LPA2 antagonist significantly reversed these effects of Gintonin. In the arthritis rat model, Gintonin suppressed all parameters that were measured. Conclusion: This study suggests that LPA2 receptor plays a key role in mediating the anti-arthritic effects of Gintonin by modulating inflammatory mediators, the MAPK and NF-κB signaling pathways.

• Journal of Microbiology and Biotechnology
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• v.32 no.1
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• pp.81-90
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• 2022

Peucedanum japonicum Thunberg (PJT) has been used in traditional medicine to treat colds, coughs, fevers, and other inflammatory diseases. The goal of this study was to investigate whether 3'-isovaleryl-4'-senecioylkhellactone (IVSK) from PJT has anti-inflammatory effects on lung epithelial cells. The anti-inflammatory effects of IVSK were evaluated using phorbol 12-myristate 13-acetate (PMA)-stimulated A549 cells and regular human lung epithelial cells as a reference. IVSK reduced the secretion of the inflammatory mediators interleukin (IL)-8 and monocyte chemoattractant protein-1 (MCP-1), and the mRNA expression of IL-6, IL-8, MCP-1, and IL-1β. Additionally, it inhibited the phosphorylation of IκB kinase (IKK), p65, Iκ-Bα, and mitogen-activated protein kinases (MAPKs) p38, JNK, and ERK in A549 cells stimulated with PMA. Moreover, the binding affinity of activator protein-1 (AP-1) and nuclear factor-κB (NF-κB) was significantly reduced in the luciferase assay, while nuclear translocation was markedly inhibited by IVSK in the immunocytochemistry. These findings indicate that IVSK can protect against inflammation through the AP-1 and NF-κB pathway and could possibly be used as a lead compound for the treatment of inflammatory lung diseases.

• Journal of Microbiology and Biotechnology
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• v.18 no.7
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• pp.1308-1316
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• 2008

Propionibacterium acnes is known to playa pivotal role in the pathogenesis of acne vulgaris. CBT-SL5 is one of the antimicrobial peptides from Enterococcus faecalis SL5, and it has shown antimicrobial activity against P. acnes. The aim of this study was to investigate the anti-inflammatory effect of CBT-SL5 on the inflammation induced by P. acnes in cultured human keratinocyes. Cultured human keratinocytes derived from neonatal foreskin were treated with heat-killed P. acnes to induce inflammation, and then various concentrations of CBT-SL5 were added to the P. acnes-treated keratinocytes. The mRNA expression and protein secretion of interleukin (IL)-8, an inflammation marker, was analyzed by real-time reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. We also analyzed the nuclear factor-kappa B (NF-$\kappaB$) p65 translocation by performing immunofluorescent staining. P. acnes treatment up regulated the IL-8 mRNA expression in the keratinocytes, and this was brought about through both toll-like receptor (TLR)2 and TLR4. At the concentrations of 10, 50, and 100 ng/ml, CBT-SL5 significantly down regulated the P. acnes-induced IL-8 mRNA expression and protein production (p<0.05). At 6 hand 12 h of the treatment, CBT-SL5 significantly suppressed the P. acnes-induced IL-8 mRNA expression. Secretion of IL-8 protein was significantly reduced at 24 h. The functional inhibitory activity of CBT-SL5 was shown by CBT-SL5 suppressing the P. acnes-induced NF-$\kappaB$ translocation from the cytoplasm to the nucleus. These results demonstrated that CBT-SL5 suppressed the P. acnes-induced IL-8 expression in keratinocytes. Therefore, CBT-SL5 may be a novel anti-inflammatory treatment for acne.

• Advances in Traditional Medicine
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• v.10 no.2
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• pp.116-122
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• 2010

Saengmaeksan (SMS) is a well known Korean traditional herbal prescription, which consists of 3 different herbs, Radix Ophiopogonis, Radix Ginseng, and Fructus Schisandrae. SMS has been commonly used in various disease including respiratory system and cardiovascular System in Korea. The objective of this study is to find out the improving effects of SMS against Dextran Sulfate Sodium (DSS)-induced ulcerative colitis. SMS reduced clinical signs of DSS-induced colitis, including body weight loss, shorten colon length, and increased disease activity index. The results showed that SMS significantly inhibited the activation of nuclear factor-${\kappa}B$ p65 in the colon tissues of DSS-treated mice. In addition, we observed that result showed that the levels of IL-6 in plasma were increased in DSS treated group compared to those of the normal group, but these increased levels were reduced by administration with SMS. Taken together, these findings suggest that SMS has improving effects on DSS-induced ulcerative colitis, which may explain its beneficial effect in the regulation of chronic intestinal inflammation.

• Journal of Physiology & Pathology in Korean Medicine
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• v.32 no.6
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• pp.396-402
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• 2018

Hataedock (HTD) treatment is a traditional preventive therapy for the fetal toxicosis- the acute allergic disease after childbirth, mainly manifested by a variety of skin allergies such as scab, phlegm. The aim of this study was to investigate the efficacy of HTD treatments for the alleviation of inflammation in Dermatophagoides farinae-induced obese NC/Nga mice. 20 mg/kg of Coptidis Rhizoma, Glycyrrhizae Radix (CRGR) extracts as a remedy of HTD treatments were orally administered to NC/Nga mice. We induced obesity in the mice by high-fat diet. To induce skin allergies, the extracts of Dermatophagoides farinae were topically applied on the NC/Nga mice at 4th-6th and 8th-10th weeks. Structural and molecular changes in the skin tissues were measured by immunohistochemical staining. HTD treatment decreased the atopic dermatitis (AD)-like symptoms including hemorrhage, erythema, erosion, edema, and dryness. HTD treatment suppressed the mast cell activation confirmed by reduction of $Fc{\varepsilon}RI$, substance P, and serotonin. The expression of several inflammatory mediators including nuclear factor-kappa B ($NF-{\kappa}B$) p65, inducible nitric oxide synthase (iNOS), vascular endothelial growth factors (VEGFs) was also decreased by HTD treatment. HTD treatment suppressed the allergic, inflammatory responses in the skin tissues of the NC/Nga mice by reducing mast cells and down-regulating several inflammatory mediators.

• Journal of Biomedical and Translational Research
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• v.19 no.4
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• pp.65-72
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• 2018

The purpose of this study was to investigate probiotic characteristics and immune enhancing effects of Bifidobacterium (B.) longum KBB1-26 and BIF-4, B. breve KBB5-22 isolated from human intestine for probiotic use in humans and animals. We measured acid, bile and heat tolerance, antimicrobial activity against pathogenic bacteria, Escherichia (E.) coli, Salmonella (S.) Enteritidis, Staphylococcus (S.) aureus, and Listeria (L.) monocytogenes. Immune enhancing effects of B. longum and B. breve were investigated by measuring nitric oxide (NO), nuclear factor ($NF-{\kappa}b$), $interleukin-1{\beta}$ ($IL-1{\beta}$), interleukin-6 (IL-6), interleukin-12 (IL-12) and tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) in RAW 264.7 cells or RAW BLUE cells. B. longum KBB1-26 was survived at pH 2.0. B. longum KBB1-26 and BIF-4, B. breve KBB5-22 also showed tolerance to 0.3% of oxgall bile salt. B. longum KBB1-26 was able to survive at $70^{\circ}C$ and $80^{\circ}C$ for 20 min. KBB1-26 showed the antimicrobial inhibition zone to pathogenic bacteria such as E. coli (12 mm), S. Enteritidis (14 mm), S. aureus (14 mm) and L. monocytogenes (41 mm). The production of NO ($4.5{\pm}0.00{\mu}M/mL$) and $IL-1{\beta}$ ($39.7{\pm}0.55pg/mL$) of KBB1-26 significantly higher than BIF-4 and KBB5-22, respectively. In addition, KBB1-26 and KBB5-22 induce the production of high level of $TNF-{\alpha}$ and IL-6 in macrophages. Collectively, B. longum KBB1-26 have acid, bile, heat tolerance, antimicrobial activity and immune enhancing effects. These results suggest that KBB1-26 can be used as probiotics for humans and animals.

• Journal of Life Science
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• v.30 no.7
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• pp.634-639
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• 2020

Starfish are a potential source of marine materials, but their unique odor can limit application. Our previous work suggested that brittle star Ophioplocus japonicus extract could be more effective as a cosmetic material by reducing its odor through a roasting process. However, the biological properties of heat-treated Ophioplocus japonicus extract (HOJE) remain poorly understood. We here examined the anti-inflammatory potential of HOJE in lipopolysaccharide (LPS)-induced RAW 264.7 cells. HOJE significantly inhibits LPS-stimulated nitric oxide (NO) production without affecting cell viability in a dose-dependent manner and suppresses LPS-induced expression of inducible nitric oxide synthases (iNOS) and pro-inflammatory cytokines such as interleukin-6 and -1β. Furthermore, treatment of pyrrolidine dithiocarbamate to inhibit nuclear factor kappa B (NF-κB) signaling accelerated the inhibitory effect of HOJE on NO production, and the translocation of NF-κB p65 from the cytosol to the nucleus was attenuated by HOJE. These results show that HOJE ameliorates inflammation partly through NF-κB signaling which consequently suggests that it has anti-inflammatory potential.