• Title/Summary/Keyword: ${\alpha}-Factor$

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α-Lipoic Acid Inhibits Apoptosis by Suppressing the Loss of Ku Proteins in Helicobacter pylori-Infected Human Gastric Epithelial Cells

  • Dayong Park;Joo Weon Lim;Hyeyoung Kim
    • Journal of Web Engineering
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    • v.14 no.15
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    • pp.3206-3218
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    • 2022
  • Helicobacter pylori (H. pylori) is a Gram-negative bacterium that colonizes the gastric mucosa and triggers various stomach diseases. H. pylori induces reactive oxygen species (ROS) production and DNA damage. The heterodimeric Ku70/Ku80 protein plays an essential role in the repair of DNA double-strand breaks (DSB). Oxidative stress stimulate apoptosis and DNA damage that can be repaired by Ku70/80. However, excessive reactive oxygen species (ROS) can cause Ku protein degradation, resulting in DNA fragmentation and apoptosis. α-lipoic acid (α-LA), which is found in organ meats such as liver and heart, spinach, broccoli, and potatoes, quenches free radicals, chelates metal ions, and reduces intracellular DNA damage induced by oxidative stress. Here, we investigated whether H. pylori decreases Ku70/80 and induces apoptosis, and whether α-LA inhibits changes induced by H. pylori. We analyzed ROS, DNA damage markers (γ-H2AX, DNA fragmentation), levels of Ku70/80, Ku-DNA binding activity, Ku80 ubiquitination, apoptosis indices (Bcl-2, Bax, apoptosis-inducing factor (AIF), and caspase-3), and viability in a human gastric epithelial adenocarcinoma cell line (AGS). H. pylori increased ROS, DNA damage markers, Ku80 ubiquitination, and consequently induced apoptosis. It also decreased nuclear Ku70/80 levels and Ku-DNA-binding activity; increased Bax expression, caspase-3 cleavage, and truncated AIF; but decreased Bcl-2 expression. These H. pylori-induced alterations were inhibited by α-LA. The antioxidant N-acetylcysteine and proteasome inhibitor MG-132 suppressed H. pylori-induced cell death and decreased nuclear Ku70/80 levels. The results show that oxidative stress induced Ku70/80 degradation via the ubiquitin-proteasome system, leading to its nuclear loss and apoptosis in H. pylori-infected cells. In conclusion, α-LA inhibited apoptosis induced by H. pylori by reducing ROS levels and suppressing the loss of Ku70/80 proteins in AGS cells.

A Hydrodistillate of Gynostemma pentaphyllum and Damulin B Prevent Cisplatin-Induced Nephrotoxicity In Vitro and In Vivo via Regulation of AMPKα1 Transcription

  • Minhyeok Song;Minseok Kim;Dang Hieu Hoang;Lochana Mangesh Kovale;Jihyun Lee;Youngjoo Kim;Changhyun Lee;Jongki Hong;Sungchul Park;Wonchae Choe;Insug Kang;Sung Soo Kim;Joohun Ha
    • Journal of Web Engineering
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    • v.14 no.23
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    • pp.4997-5013
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    • 2022
  • The clinical application of cisplatin, one of the most effective chemotherapeutic agents used to treat various cancers, has been limited by the risk of adverse effects, notably nephrotoxicity. Despite intensive research for decades, there are no effective approaches for alleviating cisplatin nephrotoxicity. This study aimed to investigate the protective effects and potential mechanisms of a Gynostemma pentaphyllum leaves hydrodistillate (GPHD) and its major component, damulin B, against cisplatin-induced nephrotoxicity in vitro and in vivo. A hydro-distillation method can extract large amounts of components within a short period of time using non-toxic, environmentally friendly solvent. We found that the levels of AMP-activated protein kinase α1 (AMPKα1), reactive oxygen species (ROS), and apoptosis were tightly associated with each other in HEK293 cells treated with cisplatin. We demonstrated that AMPKα1 acted as an anti-oxidant factor and that ROS generated by cisplatin suppressed the expression of AMPKα1 at the transcriptional level, thereby resulting in induction of apoptosis. Treatment with GPHD or damulin B effectively prevented cisplatin-induced apoptosis of HEK293 cells and cisplatin-induced acute kidney injury in mice by suppressing oxidative stress and maintaining AMPKα1 levels. Therefore, our study suggests that GPHD and damulin B may serve as prospective adjuvant agents against cisplatin-induced nephrotoxicity.

Antioxidant, anti-inflammatory, and anti-fibrotic properties of olive leaf extract protect against L-arginine induced chronic pancreatitis in the adult male albino rat

  • Ghada Hamed Romeh;Fatma El-Nabawia Abdel-Hady El-Safty;Abeer El-Said El-Mehi;Manar Ali Faried
    • Anatomy and Cell Biology
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    • v.55 no.2
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    • pp.205-216
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    • 2022
  • Chronic pancreatitis (CP) is an inflammatory disease affects the pancreas with upcoming fibrosis and notable parenchymal destruction. CP poses a high risk for pancreatic carcinoma. The present study aimed to investigate, for the first time up to our knowledge, the effect of olive leaf extract on L-arginine induced CP with referral to some of its underlying mechanisms. Forty adult male albino rats were divided equally into four groups; control, olive leaf extract treated (200 mg/kg orally once daily), CP group (300 mg L-arginine/100 g body weight intraperitoneally, once daily for 3 weeks then every 3 days for the subsequent 3 weeks), and CP treated with olive leaf extract group. At the end of the experiment, body weight, serum glucose, serum insulin, homeostatic model assessment of insulin resistance (HOMA-IR), serum amylase and lipase as well as tissue superoxide dismutase (SOD), and malondialdehyde (MDA) levels were assessed. Pancreatic tissues were subjected to histological and immuno-histochemical studies. The CP group revealed significant decrease in body weight and increase in serum glucose, serum insulin, HOMA-IR score, serum amylase, and serum lipase levels. Significant increase in MDA level and decrease in SOD level were detected. Marked degenerative changes and fibrosis were detected. Upregulation of alpha smooth muscle actin (α-SMA), transforming growth factor beta (TGF-β), caspase-3, and interleukin-6 (IL-6) immunoreactions were implicated in CP pathogenesis. Olive leaf extract alleviated all the examined parameters via its-antioxidant, anti-inflammatory, and anti-fibrotic properties. Olive leaf extract can protect against CP and restore pancreatic functions.

The Effects of the Computer Aided Innovation Capabilities on the R&D Capabilities: Focusing on the SMEs of Korea (Computer Aided Innovation 역량이 연구개발역량에 미치는 효과: 국내 중소기업을 대상으로)

  • Shim, Jae Eok;Byeon, Moo Jang;Moon, Hyo Gon;Oh, Jay In
    • Asia pacific journal of information systems
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    • v.23 no.3
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    • pp.25-53
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    • 2013
  • This study analyzes the effect of Computer Aided Innovation (CAI) to improve R&D Capabilities empirically. Survey was distributed by e-mail and Google Docs, targeting CTO of 235 SMEs. 142 surveys were returned back (rate of return 60.4%) from companies. Survey results from 119 companies (83.8%) which are effective samples except no-response, insincere response, estimated value, etc. were used for statistics analysis. Companies with less than 50billion KRW sales of entire researched companies occupy 76.5% in terms of sample traits. Companies with less than 300 employees occupy 83.2%. In terms of the type of company business Partners (called 'partners with big companies' hereunder) who work with big companies for business occupy 68.1%. SMEs based on their own business (called 'independent small companies') appear to occupy 31.9%. The present status of holding IT system according to traits of company business was classified into partners with big companies versus independent SMEs. The present status of ERP is 18.5% to 34.5%. QMS is 11.8% to 9.2%. And PLM (Product Life-cycle Management) is 6.7% to 2.5%. The holding of 3D CAD is 47.1% to 21%. IT system-holding and its application of independent SMEs seemed very vulnerable, compared with partner companies of big companies. This study is comprised of IT infra and IT Utilization as CAI capacity factors which are independent variables. factors of R&D capabilities which are independent variables are organization capability, process capability, HR capability, technology-accumulating capability, and internal/external collaboration capability. The highest average value of variables was 4.24 in organization capability 2. The lowest average value was 3.01 in IT infra which makes users access to data and information in other areas and use them with ease when required during new product development. It seems that the inferior environment of IT infra of general SMEs is reflected in CAI itself. In order to review the validity used to measure variables, Factors have been analyzed. 7 factors which have over 1.0 pure value of their dependent and independent variables were extracted. These factors appear to explain 71.167% in total of total variances. From the result of factor analysis about measurable variables in this study, reliability of each item was checked by Cronbach's Alpha coefficient. All measurable factors at least over 0.611 seemed to acquire reliability. Next, correlation has been done to explain certain phenomenon by correlation analysis between variables. As R&D capabilities factors which are arranged as dependent variables, organization capability, process capability, HR capability, technology-accumulating capability, and internal/external collaboration capability turned out that they acquire significant correlation at 99% reliability level in all variables of IT infra and IT Utilization which are independent variables. In addition, correlation coefficient between each factor is less than 0.8, which proves that the validity of this study judgement has been acquired. The pair with the highest coefficient had 0.628 for IT utilization and technology-accumulating capability. Regression model which can estimate independent variables was used in this study under the hypothesis that there is linear relation between independent variables and dependent variables so as to identify CAI capability's impact factors on R&D. The total explanations of IT infra among CAI capability for independent variables such as organization capability, process capability, human resources capability, technology-accumulating capability, and collaboration capability are 10.3%, 7%, 11.9%, 30.9%, and 10.5% respectively. IT Utilization exposes comprehensively low explanatory capability with 12.4%, 5.9%, 11.1%, 38.9%, and 13.4% for organization capability, process capability, human resources capability, technology-accumulating capability, and collaboration capability respectively. However, both factors of independent variables expose very high explanatory capability relatively for technology-accumulating capability among independent variable. Regression formula which is comprised of independent variables and dependent variables are all significant (P<0.005). The suitability of regression model seems high. When the results of test for dependent variables and independent variables are estimated, the hypothesis of 10 different factors appeared all significant in regression analysis model coefficient (P<0.01) which is estimated to affect in the hypothesis. As a result of liner regression analysis between two independent variables drawn by influence factor analysis for R&D capability and R&D capability. IT infra and IT Utilization which are CAI capability factors has positive correlation to organization capability, process capability, human resources capability, technology-accumulating capability, and collaboration capability with inside and outside which are dependent variables, R&D capability factors. It was identified as a significant factor which affects R&D capability. However, considering adjustable variables, a big gap is found, compared to entire company. First of all, in case of partner companies with big companies, in IT infra as CAI capability, organization capability, process capability, human resources capability, and technology capability out of R&D capacities seems to have positive correlation. However, collaboration capability appeared insignificance. IT utilization which is a CAI capability factor seemed to have positive relation to organization capability, process capability, human resources capability, and internal/external collaboration capability just as those of entire companies. Next, by analyzing independent types of SMEs as an adjustable variable, very different results were found from those of entire companies or partner companies with big companies. First of all, all factors in IT infra except technology-accumulating capability were rejected. IT utilization was rejected except technology-accumulating capability and collaboration capability. Comprehending the above adjustable variables, the following results were drawn in this study. First, in case of big companies or partner companies with big companies, IT infra and IT utilization affect improving R&D Capabilities positively. It was because most of big companies encourage innovation by using IT utilization and IT infra building over certain level to their partner companies. Second, in all companies, IT infra and IT utilization as CAI capability affect improving technology-accumulating capability positively at least as R&D capability factor. The most of factor explanation is low at around 10%. However, technology-accumulating capability is rather high around 25.6% to 38.4%. It was found that CAI capability contributes to technology-accumulating capability highly. Companies shouldn't consider IT infra and IT utilization as a simple product developing tool in R&D section. However, they have to consider to use them as a management innovating strategy tool which proceeds entire-company management innovation centered in new product development. Not only the improvement of technology-accumulating capability in department of R&D. Centered in new product development, it has to be used as original management innovative strategy which proceeds entire company management innovation. It suggests that it can be a method to improve technology-accumulating capability in R&D section and Dynamic capability to acquire sustainable competitive advantage.

Beneficial Effects of Daebong Persimmon against Oxidative Stress, Inflammation, and Immunity in vivo (대봉감의 항산화, 항염증 및 면역증강 효과)

  • Lee, Hee Jae;Lim, So Young;Kang, Min-Gyung;Park, Jeongjin;Chung, Hyun-Jung;Yang, Soo Jin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.4
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    • pp.491-496
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    • 2015
  • The purpose of this study was to assess the antioxidant, anti-inflammatory, and immuno-enhancing effects of Daebong persimmon (DP) and Bansi (BS) in vivo. Two types of astringent persimmons (DP and BS) were used for this experiment. C57BL/6J mice were assigned to the following groups: 1) lean control, 2) high-fat diet control (HF), 3) A region DP (3% wt/wt) with HF diet (A-DP), 4) B region DP with HF diet (B-DP), 5) C region DP with HF diet (C-DP), 6) D region BS with HF diet (D-BS), and 7) E region BS with HF diet (E-BS). All mice were sacrificed after 4 weeks of treatment, after which blood and tissues were collected. Antioxidant enzyme activities, inflammatory markers, and immune factors were evaluated. DP and BS treatments did not alter food intake or body weight, compared with HF. Administration of B-DP increased catalase activities in serum. Hepatic levels of malondialdehyde, a product of lipid peroxidation, were significantly lower in A-DP mice than in the HF group. A-DP had down-regulatory effects against inflammation induced by high-fat diet feeding, as shown by significant reduction of interleukin (IL)-$1{\beta}$, IL-6, and tumor necrosis factor-${\alpha}$. Additionally, A-DP treatment exerted an immuno-stimulatory effect, as shown by increasing levels of immunoglobulin G. DP treatment improved the level of insulin-like growth factor-1. These results indicate that DP has beneficial health effects on oxidative stress, inflammation, and immunity in vivo.

The Role of Uteroglobin in the Immunomodulation of Nonsmall Cell Lung Cancer Cells (비소세포 폐암세포에서 Uteroglobin의 면역 조절 기능에 대한 연구)

  • Yoon, Jung Min;Lim, Jae-Jun;Yoo, Chul-Gyu;Lee, Choon-Taek;Han, Sung Koo;Shim, Young-Soo;Kim, Young Whan
    • Tuberculosis and Respiratory Diseases
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    • v.57 no.4
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    • pp.336-344
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    • 2004
  • Background : Immunotherapy for cancer has not been successful because of several obstacles in tumor and its environment. Inappropriate secretions of cytokines and growth factors by tumors cause substantial changes in the immune responses against tumors, affording the tumors some degree of protection from immune attack. Uteroglobin (UG, Clara cell secretory protein) has been known to have anti-inflammatory, immunomodulatory and anti-cancer activities. However, in lung cancer cells, UG expression is decreased. This study investigated the role of UG in the immunomodulation of lung cancer. Methods : The UG protein was overexpressed by Adenovirus(Ad)-UG transduction in non-small cell lung cancer cell lines. The concentration of Prostaglandin $E_2$ ($PGE_2$) was measured by Enzyme Immunoassay (EIA). Peripheral blood mononuclear cells (PBMC) from whole blood were prepared with Ficoll. PBMC were cultured in RPMI 1640, supernatant of A549, or A549 with UG or NS-398. Concentration of Th 1 type and Th 2 type cytokines from PBMC were measured by ELISA. Results : UG suppressed $PGE_2$, Cyclooxygenase-2 (COX-2) product. Both Th1 type such as Interleukin-2 (IL-2), Interferon-${\gamma}$ (IFN-${\gamma}$) and Tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and Th2 type cytokines such as IL-10 and Tumor growth factor-${\beta}$ (TGF-${\beta}$) were increased when PBMC were cultured with supernatant of non small lung cancer cells. UG and COX-2 inhibitor, NS-398 induced normal immune response of PBMC. Although Th 1 type cytokines were increased, Th 2 type cytokines were reduced by UG. Conclusion : UG suppressed PGE2, COX-2 product. Supernatant of NSCLC induced imbalance of immune response of PBMC. However, UG reversed this imbalance. These results suggest that UG may be used in the development of immunotherapy for lung cancer.

Biological Activities of Extracts from Cornus kousa Fruit (산딸나무(Cornus kousa) 열매 추출물의 생리활성)

  • Lee, Eun-Ho;Lee, Seon-Ho;Cho, Young-Je
    • Journal of Applied Biological Chemistry
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    • v.58 no.4
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    • pp.317-323
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    • 2015
  • The extracted phenolic compounds from Cornus kousa fruit for biological activities as functional resources were examined. The phenolic compounds which were extracted with water and 40% ethanol from Cornus kousa fruit were $7.04{\pm}0.27$ and $4.47{\pm}0.18mg/g$, respectively. The 1,1-diphenyl-2-picrylhydrazyl free radical scavenging activity of water and ethanol extracts were 84% and 86% at $50{\mu}g/mL$phenolics, respectively. The 2,2'-Azinobis-(3-ethylbenzothiazoline-6-sulfonic acid radical decolorization activity of water and ethanol extracts were 84 and 95% at $100{\mu}g/mL$ phenolics, respectively. Antioxidant protection factor in water and ethanol extracts at $50{\mu}g/mL$ phenolics were 1.93 and 1.82 PF, respectively. Thiobarbituric acid reactive substance were 69% in water extracts and 89% in ethanol extracts at $150{\mu}g/mL$ phenolics. The inhibition activity on xanthine oxidase in water and ethanol extracts was 34 and 60%, respectively. The inhibition activity on ${\alpha}$-glucosidase was 29% in water extracts and 87% in ethanol extracts. The tyrosinase inhibitory activity was 19% in ethanol extracts. The collagenase inhibition activity of anti-wrinkle effect showed an excellent wrinkle improvement effect as 53% in water extracts and 77% in ethanol extracts at $200{\mu}g/mL$ phenolics. The hyaluronidase inhibition activity as antiinflammation effect of water extracts was confirmed to 34% of inhibition at $200{\mu}g/mL$ phenolic. The results can be expected extracts from Cornus kousa fruit to use as functional resource for antioxidant, antigout, inhibitor of carbohydrate degradation, antiwrinkle activity and antiinflammation activity.

Structural analysis of the Social Support, Career Capability, Career Decision-making Self-Efficacy and Career Adaptability for the Reemployment Women (재취업여성이 지각한 사회적지지, 진로역량 진로결정자기효능감 및 진로적응성 간의 구조적 관계 분석)

  • Shin, Su-Jeong;Lee, In-Hee
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.19 no.8
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    • pp.422-432
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    • 2018
  • This study is designed to find out the causal relation between social support, career capability, career decision-making self-efficacy and career adaptability for the career interrupted women. For this purposes the scales of social support, career capability, career decision related self efficacy and career adaptability were used. For this study, the questionnaires were distributed from Mar. 2, 2018 to Apr. 6, 2018 to 960 to the career interrupted women who had the experience of getting training at the vocational school, beauty school and women's centers located in Seoul and Gyeonggi area (composed of married women in their 30s and 50s who were receiving the education of beauty care for more than 1-9 months). 920 questionnaires got responded from the women and they were used for the final analysis with Cronbach's ${\alpha}$, exploratory factor analysis, factor analysis, frequency analysis and correlation analysis performed with SPSS program and the structural equation performed with AMOS program. The findings from the analysis are as follows; First, it was found that the structural model between career capability, social support, career decision related self efficacy and career adaptability are proper. Second, the path coefficient of the structural model was found to be statistically significant with respect to all of career capability, social support, career decision related self efficacy and career adaptability. Third, it was found that in the relation between career capability, social support and career adaptability, the career decision related self efficacy has the mediating effect. These results show that if the level of career adaptability is to be enhanced for the caber interrupted women, the career decision related self efficacy can make the critical role in addition to the career capability and social support. So, this study tries to offer the basic data required for the preparation of career and the development of future career for the success of career interrupted women going back to the workplace.

Effect of Dietary Krill Meal Levels on Performance and Immune Response of Broiler Chicks Injected with Salmonella typhimurium Lipopolysaccharide (살모넬라 LPS를 주입한 육계병아리에 있어서 사료 중 크릴 밀 수준이 생산성과 면역반응에 미치는 영향)

  • Im, J.T.;Park, I.K.;Koh, T.S.
    • Journal of Animal Science and Technology
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    • v.49 no.2
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    • pp.225-238
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    • 2007
  • In this study, the effects of dietary krill meal levels on cellular immunity in LPS-injected broiler chicks was evaluated. One day-old male broiler chicks(Ross) were fed on the experimental basal meal(0.0% krill meal), or diets containing 0.5%, 1.0% and 2.0% krill for 3 weeks, and the acute phase response was activated by intraperitoneally injection of Salmonella typhimurium lipopolysaccharide(LPS) 3 times at 9, 11, and 13 days of age. 1. Acute phase response induced a significant reduction in(p<0.05) daily weight gain and feed intake, and increases in liver and spleen weight. However, it was not affected by dietary krill meal levels. 2. The krill meal diets reduced TNF-α activity as compared to the basal diet after 24 hours (acute phase response) and 1 week(recovery from the acute phase response) following LPS injection (p<0.05). The acute phase response induced a significant increase(p<0.05) in TNF-α activity relative to the control in chicks fed on a basal diet, but this was also unaffected by dietary krill meal levels. 3. Acute phase response-mediated ovotransferrin levels(relative to what was measured in the control bird) were increased in birds fed on the basal, 1.0% and 2.0% krill diets, and were reduced in birds fed on the 0.5 % krill diet. 4. In LPS-injected chicks, 1.0% and 2.0% krill meal diets induced a significant reduction in(p<0.05) the Con A-induced proliferation of PBMC and splenocytes relative to what was observed in the chicks fed on a 0.5% krill diet, whereas the splenocytes proliferated in a linear fashion with the krill levels in the diets of the control birds. The results showed that the dietary levels of krill meal reduced TNF-α activity in the blood and also influenced blood ovotransferrin levels and the proliferation of PBMC and splenocytes, and krill meal is considered to be associated with both innate and cellular immunity in broiler chicks.

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.