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Respiratory protective effects of Korean Red Ginseng in a mouse model of particulate matter 4-induced airway inflammation

  • Won-Kyung Yang;Sung-Won Kim;Soo Hyun Youn;Sun Hee Hyun;Chang-Kyun Han;Yang-Chun Park;Young-Cheol Lee;Seung-Hyung Kim
    • Journal of Ginseng Research
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    • v.47 no.1
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    • pp.81-88
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    • 2023
  • Background: Air pollution has led to an increased exposure of all living organisms to fine dust. Therefore, research efforts are being made to devise preventive and therapeutic remedies against fine dust-induced chronic diseases. Methods: Research of the respiratory protective effects of KRG extract in a particulate matter (PM; aerodynamic diameter of <4 ㎛) plus diesel exhaust particle (DEP) (PM4+D)-induced airway inflammation model. Nitric oxide production, expression of pro-inflammatory mediators and cytokines, and IRAK-1, TAK-1, and MAPK pathways were examined in PM4-stimulated MH-S cells. BALB/c mice exposed to PM4+D mixture by intranasal tracheal injection three times a day for 12 days at 3 day intervals and KRGE were administered orally for 12 days. Histological of lung and trachea, and immune cell subtype analyses were performed. Expression of pro-inflammatory mediators and cytokines in bronchoalveolar lavage fluid (BALF) and lung were measured. Immunohistofluorescence staining for IRAK-1 localization in lung were also evaluated. Results: KRGE inhibited the production of nitric oxide, the expression of pro-inflammatory mediators and cytokines, and expression and phosphorylation of all downstream factors of NF-κB, including IRAK-1 and MAPK/AP1 pathway in PM4-stimulated MH-S cells. KRGE suppressed inflammatory cell infiltration and number of immune cells, histopathologic damage, and inflammatory symptoms in the BALF and lungs induced by PM4+D; these included increased alveolar wall thickness, accumulation of collagen fibers, and TNF-α, MIP2, CXCL-1, IL-1α, and IL-17 cytokine release. Moreover, PM4 participates induce alveolar macrophage death and interleukin-1α release by associating with IRAK-1 localization was also potently inhibited by KRGE in the lungs of PM4+D-induced airway inflammation model. KRGE suppresses airway inflammatory responses, including granulocyte infiltration into the airway, by regulating the expression of chemokines and inflammatory cytokines via inhibition of IRAK-1 and MAPK pathway. Conclusion: Our results indicate the potential of KRGE to serve as an effective therapeutic agent against airway inflammation and respiratory diseases.

Morin Hydrate Inhibits Influenza Virus entry into Host Cells and Has Anti-inflammatory Effect in Influenza-infected Mice

  • Eun-Hye Hong;Jae-Hyoung Song;Seong-Ryeol Kim;Jaewon Cho;Birang Jeong;Heejung Yang;Jae-Hyeon Jeong;Jae-Hee Ahn;Hyunjin Jeong;Seong-Eun Kim;Sun-Young Chang;Hyun-Jeong Ko
    • IMMUNE NETWORK
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    • v.20 no.4
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    • pp.32.1-32.15
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    • 2020
  • Influenza virus is the major cause of seasonal and pandemic flu. Currently, oseltamivir, a potent and selective inhibitor of neuraminidase of influenza A and B viruses, is the drug of choice for treating patients with influenza virus infection. However, recent emergence of oseltamivir-resistant influenza viruses has limited its efficacy. Morin hydrate (3,5,7,2',4'-pentahydroxyflavone) is a flavonoid isolated from Morus alba L. It has antioxidant, anti-inflammatory, neuroprotective, and anticancer effects partly by the inhibition of the NF-κB signaling pathway. However, its effects on influenza virus have not been studied. We evaluated the antiviral activity of morin hydrate against influenza A/Puerto Rico/8/1934 (A/PR/8; H1N1) and oseltamivir-resistant A/PR/8 influenza viruses in vitro. To determine its mode of action, we carried out time course experiments, and time of addition, hemolysis inhibition, and hemagglutination assays. The effects of the co-administration of morin hydrate and oseltamivir were assessed using the murine model of A/PR/8 infection. We found that morin hydrate reduced hemagglutination by A/PR/8 in vitro. It alleviated the symptoms of A/PR/8-infection, and reduced the levels of pro-inflammatory cytokines and chemokines, such as TNF-α and CCL2, in infected mice. Co-administration of morin hydrate and oseltamivir phosphate reduced the virus titers and attenuated pulmonary inflammation. Our results suggest that morin hydrate exhibits antiviral activity by inhibiting the entry of the virus.

Fermented Protaetia brevitarsis Larvae Ameliorates Chronic Ethanol-Induced Hepatotoxicity in Mice via AMPK and TLR-4/TGF-β1 Pathways

  • Hyo Lim Lee;Jong Min Kim;Min Ji Go;Seung Gyum Joo;Tae Yoon Kim;Han Su Lee;Ju Hui Kim;Jin-Sung Son;Ho Jin Heo
    • Journal of Microbiology and Biotechnology
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    • v.34 no.3
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    • pp.606-621
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    • 2024
  • This study evaluated the hepatoprotective effect of fermented Protaetia brevitarsis larvae (FPB) in ethanol-induced liver injury mice. As a result of amino acids in FPB, 18 types of amino acids including essential amino acids were identified. In the results of in vitro tests, FPB increased alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities. In addition, FPB treatment increased cell viability on ethanol- and H2O2-induced HepG2 cells. FPB ameliorated serum biomarkers related to hepatoxicity including glutamic oxaloacetic transaminase, glutamine pyruvic transaminase, total bilirubin, and lactate dehydrogenase and lipid metabolism including triglyceride, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. Also, FPB controlled ethanol metabolism enzymes by regulating the protein expression levels of ADH, ALDH, and cytochrome P450 2E1 in liver tissue. FPB protected hepatic oxidative stress by improving malondialdehyde content, reduced glutathione, and superoxide dismutase levels. In addition, FPB reversed mitochondrial dysfunction by regulating reactive oxygen species production, mitochondrial membrane potential, and ATP levels. FPB protected ethanol-induced apoptosis, fatty liver, and hepatic inflammation through p-AMP-activated protein kinase and TLR-4/NF-κB signaling pathways. Furthermore, FPB prevented hepatic fibrosis by decreasing TGF-β1/Smad pathway. In summary, these results suggest that FPB might be a potential prophylactic agent for the treatment of alcoholic liver disease via preventing liver injury such as fatty liver, hepatic inflammation due to chronic ethanol-induced oxidative stress.

Association Between the Polymorphism in the Promoter Region of Porcine A-FABP Gene and Growth Traits in Duroc Pigs (돼지 Duroc 품종에서 A-FABP promoter의 다형성과 성장형질의 연관성)

  • Han, Sang-Hyeon;Jo, In-Cheol;Lee, Jong-Eon;Kim, Hyo-Seon;Lee, Jeong-Gyu;Jeon, Jin-Tae;O, Mun-Yu;Go, Mun-Seok
    • Journal of Animal Science and Technology
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    • v.48 no.1
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    • pp.21-28
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    • 2006
  • A polymorphism was found in the promoter region of porcine adipocyte fatty acid binding protein gene(A-FABP) gene which plays a key role in the binding and transportation of free fatty acid in adipocyte and deposition of intramuscular fat. Mutation was detected a substitution(T406C) using SSCP analysis and subsequently confirmed by sequencing the fragment in Duroc pigs. This T-406C mutation might change the binding activity for transcription factor nuclear factor 1(NF1). In this population, this mutation was genotyped using HinfⅠRFLP, and found three kinds of genotypes(TT, TC, and CC) showing their frequencies of 42.3, 44.3, and 13.4%, respectively. We statistically analyzed the association between the A-FABP genotypes and growth traits and found that the body weights of the pigs containing 406C/(TC or CC) were heavier for the body weight at the age of 20 weeks than those containing genotype TT(P<0.05), but not for those at the age of 0, 3, and 10 weeks. Pigs containing genotype CC had also a higher value for the average daily gain and lower values for the date for 90kg of body weight and food conversion ratio than those of 406T/- genotype. In addition, without the significant difference of back fat thickness, there was a significant association between the existence of allele CC and lean meat and eye muscle area(P<0.05). As a result of this study, we suggest that the allele T406C in the promoter region of A-FABP gene play an important role in deposition of intramuscular fat and weight in the later growth period. This polymorphism will be an useful molecular marker for breeding of Duroc pigs.

The Clinical Characteristics of Lung Cancer in Patients with Idiopathic Pulmonary Fibrosis (특발성 폐섬유화증에 동반된 폐암 환자의 임상적 특정)

  • Park, Joo-Hun;Lee, Jin-Seong;Song, Koun-Sik;Shim, Tae-Sun;Lim, Chae-Man;Koh, Youn-Suck;Lee, Sang-Do;Kim, Woo-Sung;Kim, Won-Dong;Kim, Dong-Soon
    • Tuberculosis and Respiratory Diseases
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    • v.46 no.5
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    • pp.674-684
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    • 1999
  • Background : It has been generally known that the incidence of lung cancer is higher in the patients with idopathic pumonary fibrosis (IPF) than those in general population. The reported incidence was variable from 4.8 to 43.2%. There were controversies on the most frequent cell type (squamous cell carcinoma vs. adenocarcinoma) and no study was done about the real concordance of cancer and the fibrotic lesion. And the pulmonary fibrosis may influence not only the development of cancer but also the treatment and prognosis of the cancer, but there was no report on that point. Method : Total 63 patients ($66.8{\pm}7.8$ year, M : F=61 : 2) were diagnosed as IPF combined with lung cancer (IFF-CA) at Asan Medical Center. A retrospective analysis was done about the risk factors of the lung cancer, pulmonary function test, the site of cancer(especially the relationship of the cancer with the fibrotic lesion), the histologic types, and the stage of cancer. The histologic types were compared with those of 2,660 patients with lung cancer who were diagnosed at the same institute for the same period. The effect of IPF on the treatment of the cancer was evaluated with the survival time after the detection of lung cancer. Results : The lung cancer was found in 63(22.9%) out of 281 patients with IPF. But in most of them(45 patients), lung cancer was detected at the same time with IPF and only in 18 patients, the cancer was diagnosed during the follow-up($25.2{\pm}17.7$ months) of IPF. So in our study, 6.7% of patients with IPF developed lung cancer during the course of the disease. The age ($66.8{\pm}7.84$ vs. $63.4{\pm}11.1$ years), percentage of smoker (88.9 vs. 67.2%), and the male gender (96.8 vs. 67.6%) were significantly higher in IPF-CA compared with lone IPF (p<0.05). The odds ratio of smoking was 4.7 compared with non smoking IPF controls. The lung cancer was located more frequently in the upper lobe and 55.5% was in the periphery of lung. The cancer was developed in the fibrotic lesion in 23 patients (35.9%), and in the majority of the patients, the cancer was separated from the fibrosis. The cell type of the lung cancer in IPF-CA was squamous cell carcinoma 34.9%, adenocarcinoma 30.2%, small cell carcinoma 19.0%, large cell undifferenciated carcinoma 6.3%, and others 9.5%. No significant difference in the distribution of histologic type of the lung cancer was found between IPF-CA and lone lung cancer. There was no significant difference in demographic features, cell types, location and the stage of the cancer between the group with concurrent IPF-CA and the group with cancer diagnosed during the follow up of IPF. There was a tendency (but statistically not significant : p=0.081) of higher incidence of adenocarcinoma among the cancers developed in the fibrotic area(43.5%) (F-CA) than in the cancers in non-fibrotic area (22.5%) (NF-CA). The prognosis of the patients with F-CA was poor (median survival : 4 months) compared with the patients with NF-CA (7 months, p=0.013), partly because the prevalence of severe IPF (the extent of fibrosis in HRCT 50%) was higher in F-CA group. Conclusion : These data suggest that the lung cancer in the patients with IPF has similar features to the ordinary lung cancer.

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The Effect of Application Levels of Slurry Composting and Bio-filtration Liquid Fertilizer on Soil Chemical Properties and Growth of Radish and Corn (총각무와 옥수수 재배시 SCB액비 시용수준이 토양화학성과 생육에 미치는 영향)

  • Kang, Seong-Soo;Kim, Min-Kyeong;Kwon, Soon-Ik;Kim, Myong-Suk;Yoon, Sung-Won;Ha, Sang-Gun;Kim, Yoo-Hak
    • Korean Journal of Soil Science and Fertilizer
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    • v.44 no.6
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    • pp.1306-1313
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    • 2011
  • A liquid fertilizer treated with slurry composting and biofiltration (SCB) process has been applied increasingly on agricultural field but the effects on the soil properties and crop production has not been throughly evaluated. This study was conducted to investigate the effect of the SCB application on soil chemical properties and the growth of radish and corn. SCB liquid fertilizer as a basal fertilization was treated with five levels based on $6kg\;10a^{-1}$ for radish and $10kg\;10a^{-1}$ for corn. The experimental design was the completely randomized block design with five levels and three replicates. Electrical conductivity (EC), $NO_3$-N, Exch. K and Exch. Na increased depending on the treatment levels of SCB. There were no changes in soil organic matter, Avail. $P_2O_5$, Exch. Ca and Exch. Mg. EC, $NO_3$-N and Exch. Na content decreased as precipitation increased. Especially, they decreased up to the initial condition before the treatment after the heavy rainy season in 2008. Although Exch. K decreased at the rainy season, they remained relatively higher content after the experiment on August, 2008. Fresh weight and the amount of N uptake of radish increased due to the levels of SCB, but corn did not present any significant increase. It is recommended that we need to decide the proper amount of SCB as well as the application method on the field to increase the productivity and decrease environmental stress. Additional experiments also need to clarify the effect of the trace element and heavy metal accumulations due to long term application of SCB.

Tegumental ultrastructure of juvenile and adult Echinostoma cinetorchis (이전고환극구흡충 유약충 및 성충의 표피 미세구조)

  • 이순형;전호승
    • Parasites, Hosts and Diseases
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    • v.30 no.2
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    • pp.65-74
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    • 1992
  • The tegumental ultrastructure of juvenile and adult Echinostoma cinetorchis (Trematoda: Echinostomatidae) was observed by scanning electron microscopy. Three-day (juvenile) and 16-day (adult) worms were harvested from rats (Sprague-Dawley) experimentally fed the metacercariae from the laboratory-infected fresh water snail, Hippeutis cantori. The worms were fifed with 2.5% glutaraldehyde, processed routinely, and observed by an ISI Korea DS-130 scanning electron microscope. The 3-day old juvenile worms were elongated and ventrally curved, with their ventral sucker near the anterior two-fifths of the body. The head crown was bearing 37∼38 collar spines arranged in a zigzag pattern. The lips of the oral and ventral suckers had 8 and 5 type II sensory papillae respectively, and bewteen the spines, a few type III papillae were observed. Tongue or spade-shape spines were distributed anteriorly to the ventral sucker, whereas peg-like spines were distributed posteriorly and became sparse toward the posterior body. The spines of the dorsal surface were similar to those of the ventral surface. The 16-day old adults were leaf-like, and their oral and ventral suckers were located very closely. Aspinous head crown, oral and ventral suckers had type II and type III sensory papillae, and numerous type I papillae were distributed on the tegument anterior to the ventral sucker. Scale-like spines, with broad base and round tip, were distributed densely on the tegument anterior to the ventral sucker but they became sparse posteriorly. At the dorsal surface, spines were observed at times only at the anterior body. The results showed that the tegument of E. cinetorchis is similar to that of other echinostomes, but differs in the number and arrangement of collar spines, shape and distribution of tegumenal spines, and type and distribution of sensory papillae.

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Improving effect of psoriasis dermatitis by yakuchinone A in the TNF-α stimulated HaCaT cells (TNF-α 자극에 활성화된 HaCaT 세포주에서 Yakuchinone-A에 의한 건선 피부염 개선 효과)

  • Kim, Min Young;Hwang, Hyung Seo
    • Journal of Applied Biological Chemistry
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    • v.63 no.1
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    • pp.95-101
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    • 2020
  • Psoriasis is an autoimmune skin disease that is accompanied by hyper proliferation of the epidermis, erythema of various sizes, and ulceration. However, the mechanism of the development of psoriasis dermatitis is unclear. Recently, it is known that the inflammatory cytokines and Th17 cells as well as chemokine (CC motif) ligand 20 (CCL20) are involved in the process of keratinocytes hyper-differentiation, which is common in psoriasis dermatitis. Therefore, we studied the effects of yakuchinone-A, an active ingredient of Alpinia oxyphylla Miquel known for its anti-inflammatory activity, to improve psoriasis dermatitis. First, cytotoxicity of yakuchinone-A was observed in cell counting kit-8 assay and not observed in 10 ㎍/mL concentration on the human keratinocyte HaCaT cells. Yakuchinone-A in the presence of tumor necrosis factor-alpha (TNF-α) on HaCaT cells inhibited mRNA expression of IL-6, IL-8, and TNF-α by up to 61.4±7.5, 23.6±1.5, 46.0±4.8%. CCL20, a chemokine that attracts immune cells such Th17 cells to the inflammation location, was also significantly suppressed by yakuchinone-A. In addition, IκB and STAT3 phosphorylation involved in the CCL20 expression was inhibited by yakuchinone-A in a concentration-dependent manner up to the level of 79.1±5.0, 80.8±2.3%. Furthermore, yakuchinone-A downregulated CCL20 mRNA expression level on IL-17A-activated HaCaT cells as a concentration-dependent manner. Based on these results, yakuchinone-A is expected to be developed as a new material for improving psoriasis dermatitis in the future.

Der Verlust der Amtsfähigkeit bzw. des Wahlrechts und das Gebot der Individualisierung der Strafen (선거범에 대한 자격제한과 형벌개별화원칙)

  • Chung, Kwang-Hyun
    • Journal of Legislation Research
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    • no.53
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    • pp.337-374
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    • 2017
  • Wer wegen eines Wahldelikts zu Geldstrafe von mehr als 1 Million Won verurteilt wird, verliert nach ${\S}$ 18 Abs. 1 Satz 3, ${\S}$ 19 Satz 1, ${\S}$ 266 des Koreanischen Wahlgesetzes $f{\ddot{u}}r$ die Dauer von $f{\ddot{u}}nf$ Jahren die $F{\ddot{a}}higkeit$, ${\ddot{o}}ffentliche$ ${\ddot{A}}mter$ zu bekleiden und Rechte aus ${\ddot{o}}ffentlichen$ Wahlen. Bei Verurteilung zu Freiheitsstrafe wegen eines Wahldelikts ${\ddot{A}}mter$ sich die Dauer des Verlusts der $Amtsf{\ddot{a}}higkeit$ und des aktiven bzw. passiven Walhrechts auf 10 Jahre. Dies erfolgt kraft Gesetzes. Das $hei{\ss}t$, dass die Entscheidung ${\ddot{u}}ber$ das Ob und die Dauer des Verlusts nicht im Ermessen des Gerichts steht. Allerdings sollte $diesbez{\ddot{u}}glich$ nicht verkannt werden, dass ein deratriger Entzug von $Amtsf{\ddot{a}}higkeit$, $W{\ddot{a}}hlbarkeit$ u.s.w., mit dem eine Straftat geahndet werden soll, selber von Natur aus eine Art Strafen darstellt. Der im ${\S}$ 41 des Koreanischen StGB geregelte Strafen-Katalog $enth{\ddot{a}}lt$ $n{\ddot{a}}mlich$ eine zeitlich begrenzte Aberkennung des oben genannten ${\ddot{o}}ffentliche$n Rechtsstatus als eine Art Ehrenstrafen. Nicht einleuchtend ist, warum das Wesen der Sanktion $gem{\ddot{a}}{\ss}$ ${\S}$ 18 Abs. 1 Satz 3, ${\S}$ 19 Satz 1, ${\S}$ 266 des Koreanischen Wahlgesetzes, die den gleichen Zweck und die gleiche Rechtsfolge wie die im ${\S}$ 41 des Koreanischen StGB geregelte Ehrenstrafe hat, nicht als Strafe aufgefasst werden sollte. Handelt es sich bei der oben genannten Sanktion um eine Art Ehrenstrafen, so stellt sich die Anforderung, sie je nach der Eigenart der begangenen Tat bzw. des $T{\ddot{a}}ters$ zu individualisieren. Das Gebot der Individualisierung der Strafen, welches $haupts{\ddot{a}}chlich$ vom materiellen Rechtsstaatsprinzip ableitbar ist, kann im Grunde nur verwirklicht werden, wenn das Gericht dazu befugt ist, unter $Ber{\ddot{u}}cksichtigung$ der konkreten $Umst{\ddot{a}}nde$ jedes Einzelfalls ${\ddot{u}}ber$ eine angemessene Strafe zu befinden. Somit ist der kraft Gesetzes eintretenden Verlust der $Amtsf{\ddot{a}}higkeit$ und der $W{\ddot{a}}hlbarkeit$ nur schwer mit dem Gebot der Individualisierung der Strafen vereinbar. Es $w{\ddot{a}}re$ deshalb $w{\ddot{u}}nschenswert$, wenn der Gesetzgeber eine Reform in Betracht ziehen $w{\ddot{u}}rde$, welche den Ersatz des kraft Gesetzes automatisch eintretenden Entzugs der $Amtsf{\ddot{a}}higkeit$ bzw. des Wahlrechts durch die gerichtliche fakultative Aberkennung von diesen Statusrechten beinhaltet.

Anti-inflammation effect of blueberry (Vaccinium ashei) leaf extract on RAW 264.7 macrophages stimulated by lipopolysaccharide (Lipopolysaccharide에 의해 활성화된 RAW 264.7대식세포에서 블루베리 잎(Vaccinium ashei) 추출물의 항염증 효과)

  • Kim, Dong In;Kim, Hyun Jung;Yun, Jong Moon;Lee, Ji Hye;Han, So Jung;Kim, Ha Eun;Jang, Min Jung;An, Bong Jeun
    • Food Science and Preservation
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    • v.25 no.1
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    • pp.107-116
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    • 2018
  • The aim of this study is to investigate the antioxidant and intracellular anti-inflammatory efficacy of blueberry leaf extracted with hot water (BLW), 70% ethanol (BLE), and 70% acetone (BLA) in RAW 264.7 macrophages. In order to evaluate the anti-inflammatory effect of blueberry leaf extracts, RAW 264.7 macrophages were stimulated with lipopolysaccharide (LPS) to induce the production of inflammation-related factors, which were measure by Western blotting and real-time PCR methods. i-NOS, COX-2 protein, and mRNA expression showed concentration-dependent decrease. The decreases in the mRNA expression levels of interleukin-$1{\beta}$ (IL-$1{\beta}$), interleukin-6 (IL-6), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and prostaglandin $E_2$ ($PGE_2$) were concentration-dependent. Further, the antioxidant effects of blueberry leaf on total polyphenol contents, electron donating ability and $ABTS^+$ radical scavenging activity were evaluated. The total polyphenol contents of BLW, BLE, and BLA were $217.04{\pm}2.98$, $156.72{\pm}3.90$, and $182.88{\pm}3.02mg\;TAE/g$, respectively, while the electron donating abilities at $1,000{\mu}g/mL$ of BLW, BLE, and BLA were 81.7, 79.6, and 79.3%, respectively. The $ABTS^+$ radical scavenging activity was fond to be concentration dependent. The nitric oxide (NO) production inhibition activities at $50{\mu}g/mL$ of BLW, BLE, and BLA were 35.1, 42.4 and 42.7%, respectively. In conclusion, the antioxidant and anti-inflammatory test results indicate that blueberry leaf extracts (BLW, BLE, and BLA) can be used as potential anti-inflammatory agents.