• Title/Summary/Keyword: 억제인자

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DNA Methylation of Multiple Genes in Gastric Cancer: Association with CpG Island Methylator Phenotype and Helicobocter pylori Infection (위암에서 유전자 메틸화와 CpG Island Methylator Phenotype 및 Helicobacter pylori균 감염과의 연관성)

  • Jun, Kyong-Hwa;Won, Yong-Sung;Shin, Eun-Young;Cho, Hyun-Min;Im, Myoung-Goo;Chin, Hyung-Min;Park, Woo-Bae
    • Journal of Gastric Cancer
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    • v.6 no.4
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    • pp.227-236
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    • 2006
  • Purpose: Methylation of gene regulatory elements plays an important role in gene inactivation without genetic alteration. Gastric cancer is one of the tumors that exhibit a high frequency of CpG island hypermethylation. The purpose of this study was to investigate the occurrence of CpG island hypermethylation in gastric carcinoma in relation to H. pylori infection, CIMP and clincopathologic variables. Materials and Methods: We investigated the promoter methylation Status of six genes (hMLH1, p16, p14, COX-2, MGMT, E-cadherin) and CIMP in 36 gastric carcinoma tissues as well as in nontumor tissues. CIMP status was investigated by examining the methylation status of MINT 1, 2, 12, 25 and 31. The methylation status of the promoter was examined by methylation-specific PCR (MSP) and H. pylori infection was examined by histological diagnosis after staining with Warthin-Starry silver. Results: Among the 36 gastric carcinoma tissues, DNA hypermethylation was detected in the following frequencies: 14 (38.9%) for p14, 13 (36.1%) for p16, 8 (22.2%) for MGMT, 10 (27.8%) for COX-2, 21 (58.3%) for E-cadherin, and 6 (16.7%) for hMLH1. The frequencies for MINT1 and MINT25 hypermethylation were significantly higher in tumor tissues than in nontumor tissues. 16 (44.4%) of the 36 gastric carcinoma tissues were positive for the CIMP CIMP-H tumors were associated with older patients and larger tumor size than CIMP-L tumors. We found a significant association between the presence of the CIMP and hypermethylation of p16. Hypermethylation of p16 and MINT2 were significantly different when compared by age. MINT1 gene methylation was significantly associated with H. pylori infection (P=0.004). Conclusion: Our results suggest that aberrant hypermethylation of multiple tumor related genes (hMLH1, p16, p14, COX-2, MGMT, E-cadherin, MINT1, 2, 12, 25, 31) occurs frequently in gastric carcinoma tissues. The hypermethylation of MINT1 was significantly higher in the tumor tissues and was associated with H. pylori infection.

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Anti-Oxidative and Anti-Inflammatory Activities of Euptelea Pleiosperma Ethanol Extract (Euptelea pleiosperma 에탄올 추출물의 항산화 및 항염증 활성)

  • Jin, Kyong-Suk;Park, Jung Ae;Lee, Ji Young;Kang, Ji Sook;Kwon, Hyun Ju;Kim, Byung Woo
    • Microbiology and Biotechnology Letters
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    • v.42 no.2
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    • pp.170-176
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    • 2014
  • In this study, the anti-oxidative and anti-inflammatory activities of Euptelea pleiosperma ethanol extract (EPEE) were evaluated using in vitro assays and cell culture model systems. EPEE possessed a more potent scavenging activity against 1,1-diphenyl-2-picryl hydrazyl than the ascorbic acid used as a positive control. EPEE effectively suppressed lipopolysaccharide (LPS), in addition to hydrogen peroxide induced reactive oxygen species on RAW 264.7 cells. Furthermore, EPEE induced the expression of the anti-oxidative enzyme heme oxygenase 1 (HO-1) and its upstream transcription factor, nuclear factor-E2-related factor 2 (Nrf2), dose and time dependently. The modulation of HO-1 and Nrf2 expression might be regulated by mitogen-activated protein kinases and phosphatidyl inositol 3 kinase/Akt as their upstream signaling pathways. On the other hand, EPEE inhibited LPS induced nitric oxide (NO) formation without cytotoxicity. Suppression of NO formation was the result of the down regulation of inducible NO synthase (iNOS) by EPEE. Suppression of NO and iNOS by EPEE may be modulated by their upstream transcription factor, nuclear factor ${\kappa}B$, and AP-1 pathways. Taken together, these results provide important new insights into E. pleiosperma, namely that it possesses anti-oxidative and anti-inflammatory activities, indicating that it could be utilized as a promising material in the field of nutraceuticals.

Immunogenicity and Safety of Inactivated Influenza Vaccine in Healthy Korean Children and Adolescent (한국의 건강한 소아청소년을 대상으로 한 인플루엔자 사백신의 면역원성과 안전성 연구)

  • Ri, Soohyun;Kim, Mi Jeong;Kim, Yun-Kyung
    • Pediatric Infection and Vaccine
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    • v.25 no.1
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    • pp.35-44
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    • 2018
  • Purpose: This study aimed to evaluate the immunogenicity and safety of a trivalent inactivated influenza vaccine (TIV) among healthy Korean children and adolescents. Methods: From October to December 2008, 65 healthy patients aged 6 months to 18 years who visited Korea University Ansan Hospital for influenza vaccination were enrolled in this study. We measured the hemagglutinin inhibition antibody titers at baseline and 30 days after vaccinating enrollees with split influenza vaccine and calculated the seroprotection rates, geometric mean titers, and seroconversion rates. Local and systemic adverse events were assessed after vaccination. Results: The seroprotection rates against all three viral strains (A/H1N1, A/H3N2, B) were 87.7%, 89.2%, and 89.2% (${\geq}70%$), respectively; seroconversion rates were 44.6%, 73.8%, and 63.1% (${\geq}40%$), respectively; and seroconversion factors were 4.5, 8.4, and 10.5 (>2.5), respectively. The TIV immunogenicity was acceptable according to the CPMP (Committee for Proprietary Medicinal Products) criteria. Although 48 patients (73.8%) reported one or more adverse events, no severe adverse events such as anaphylaxis and convulsion were observed. Forty-two patients (64.6%) reported a local skin reaction, including redness (29.2%), pain (43.1%), or swelling (41.5%) of the injected site, and 26 (40.0%) reported a systemic reaction: fatigue (23.1%), myalgia (20.0%), headache (10.8%), arthralgia (10.8%), chills (9.2%), or fever (7.7%). Conclusions: This study shows that the immunogenicity of the TIV vaccine is acceptable. As there were no serious adverse events aside from local reactions and mild systemic reactions, this vaccine can be safely used among healthy Korean children and adolescents.

담자균류 ${\beta}$ -글루칸의 특성 및 생산

  • Hong, Eok-Gi
    • Proceedings of the Korean Society of Life Science Conference
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    • 2002.05a
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    • pp.17-22
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    • 2002
  • 지구상에는 수천종의 버섯류가 자생하고 있어 유전자원으로서의 중요성이 지대할 뿐만 아니라 기능성 식품소재 및 각종 약리 활성을 나타내는 신약개발 소재로도 크게 주목을 받고 있다. 이들 버섯은 균사체의 영양대사로 얻어지는 대사산물이 축적된 자실체의 형태로 나타나는데, 최근에 와서 자실체 및 균사체의 추출물이나 균사체 배양물이 체질개선이나 각종 병의 예방과 치료에 효과가 있는 것으로 밝혀져 건강식품이나 의약품으로서의 용도가 크게 증가하고 있는 실정이다. 특히, 담자균이 생산하는 특정 구조를 갖는 다당류는 오래전부터 종래의 화학요법제와는 달리 숙주내의 면역 기능을 부활하여 소위 면역요법제로서의 항암효과를 나타냄이 알려져왔었다. 현재까지 제약 및 의학적인 방법이 질병의 주된 치료방법으로 이용되어 왔지만 최근에 특정식품의 섭취가 만성질환의 발생을 억제 또는 지연시킨다는 연구 보고가 나오면서부터 만성질환의 치료방법으로서 식이요법을 중요하게 생각하게 되었다. 따라서 새로운 식품소재 및 가공식품의 개발을 통한 성인병 등의 각종 질병예방이 국민보건문제 해결에 필수적이다. 현재 일본 등에서는 표고버섯, 구름버섯 및 치마버섯 유래의 다당체 또는 단백다당체인 lentinan, krestin 또는 PS-K, schizophyllan 및 PSP 등이 실용화되어 높은 가격에 판매되고 있다. 국내에서도 야생 구름버섯 자실체로부터 추출한 단백 다당체인 Copolang(광동제약)이 개발되어 PS-K와 유사하게 암의 치료에 병행 사용되고 있고, 또 강력한 항암활성이 보고된 상황버섯의 균사체 추출물인 단백 다당체가 Mesima-Ex FK(한국신약)라는 상품명으로 암의 치료에 병행 사용되고 있는 것으로 알려지고 있다. 담자균류와 아울러 미생물 유래 다당체는 그 구조와 특성에 있어서 매우 다양함을 지니고 있다. 이러한 미생물 유래 다당류의 공업적 생산과 이용에 대한 연구로서는 Leuconostoc mesenteroides가 생산하는 dextran이 혈장증량제로 개발된 이래 Xanthomonas campestris가 생산하는 pullulan, Zoogloea rgmigera가 생산하는zooglan둥이 대표적인 예로 보고되고 있다. 한편, 미생물 유래 다당류는 구성당, 분자량, 화학적 구조 등과 같은 특성의 차이에 의해 많은 종류가 존재하고 있으며, 다양한 물성 및 유화제, 응고제, gel 형성제, 필름 형성제, 흡착제, 안정제, 접착제 등과 같은 용도로 광범위하게 이용되고 있다. 또한 근래에 들어서는 미생물 유래 다당체가 지니는 항암활성이 확인되어 새로운 의약품으로서의 개발 가능성이 기대된다. 그 밖에도 기존에 알려져 있는 식물 및 해조류 유래의 다당체와는 달리, 발효조를 이용한 연속배양에 의해 공업적 대량 생산이 가능하며, 더욱이 생산된 다당체의 분리 및 회수가 용이하다는 이점을 지니고 있다. 최근에 들어서는 유전공학적 기법을이용한 고생산성 변이균주 및 새로운 기능을 지닌 다당체의 개발에 관한 연구가 보고되고 있는 등 고부가가치를 지닌 새로운 바이오 소재로서의 기능 및 용도 개발에 관한 연구가 활발히 진행되고 있다. 이러한 항암 활성을 나타내는 여러 가지 담자균류중 Agaricus blazei로부터 생산되는 다당체는 고형암 이외에 S형 결장암, 난소암, 유방암, 폐암, 간암 등에 효과가 입증되었고, 천연물질에 의한 암 면역요법으로 각광을 받고 있으며, 항암 및 항virus의 완치율과 저지율에서 현재 여러가지 약효가 있는 버섯중에서도 탁원한 효과가 있는 것으로 증명되고 있다. 이들 다당체는 사이토카인을 생산시켜서 T임파구와 B임파구의 항원 특이적인 면역반응을 활성화시키고, 세포장해성 T세포와 활성화 대식세포의 세포장해 기능을 충진시켜서 암세포를 파괴시킨다. 또한 콜로니 자극인자인 사이토카인을 생산시켜서 면역담당세포의 신생을 촉진시키기도 하며, 암의 화학요법과 방사선 요법으로 저하된 백혈구를 회복시키는 역할을 한다. 따라서 최근의 연구동향은 생산된 다당체의 항암활성을 향상시키고자 하여 배양기간중에 interleukin을 의도적으로 첨가하는 경향이 있다. 이러한 항암 활성을 나타내는 담자균체 유래 다당체는 버섯의 기원에 따라 그 형태에 약간의 차이를 나타내기는 하나 그 기본 형태는 ${\beta}-(1,6)-glucosyl$ 분지를 가진 ${\beta}-(1,3)-glucan$이며, 평균 분자량은 50 ${\sim}$ 200만 정도이다. Agaricus blazei의 원산지인 브라질의 피에다데(Piedade) 지방의 환경조건(산지의 습도는 80%, 낮 기온 $35^{\circ)C$, 밤 기온 $20{\sim}25^{\circ}C$로 대단히 높으며, 정기적으로 열대지방 특유의 소나기가 내리는 지역)에서 볼 수 있듯이 Agaricus blazei의 성장 환경은 매우 까다로운 편이며, 날것으로는 보관이 잘 안되기 때문에 그 재배에 큰 어려움이 있다. 또한, 고체배양에 의해 생산된 버섯 자실체로부터 유기용매 및 열수추출 방법으로 다당체를 생산하는 방법은 균일한 형태의 버섯 자실체를 공급받기가 어렵기 때문에 다당체의 생산 수율이 낮고, 많은 노동력이 요구되는 어려움이 있다. 그러나 액체배양에 의한 다당체 생산의 경우는 고체배양에 의한 다당체 생산에 비해 일정한 조건하에서 배양이 가능하다는 장점이 있으며, 항상 균일한 균사체 및 배양액을 얻을 수 있다. 따라서 원하는 유용물질을 쉽게 획득할 수 있는 장점이 있다.

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Surgical Outcome of Patients with Ischemic Cardiomyopathy Selected by the Results of Myocardial Viability by Preoperative F-18 FDG PET (F-18 FDG 양전자단층촬영을 이용한 생존심근 평가 후 수술한 허혈성 심근병증 환자의 수술 결과)

  • Kim, Jae-Sung;Lee, Dong-Soo;Hong, Suk-Keun;Lee, Young-Tak;Kim, Yu-Kyeong;Kim, Youn-Jung;Moon, Keon-Sik;Won, Tae-Kyoung;Hwang, Hweung-Kon
    • The Korean Journal of Nuclear Medicine
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    • v.34 no.4
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    • pp.276-284
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    • 2000
  • Purpose: We investigated the operative outcome after bypass surgery in patients selected using viability criteria on F-18 FDG PET. Materials and Methods: Rest-24hr delay redistribution imaging of Tl-201 SPECT and F-18 FDG PET were performed in 11 patients. Seven of these 11 patients (6 men, 1 woman) were evaluated to have viable myocardium by F-18 FDG PET. Changes in symptoms and left ventricular ejection fraction (LVEF) after operation were evaluated. Results: In seven of 11 patients, a significant amount of viable myocardium was found on F-18 FDG PET and Tl-201 SPECT. Severity of both chest pain and dyspnea improved markedly in all patients. Mean LVEF improved from 22% to 32%. Conclusion: F-18 FDG PET could be used to select the patients who will benefit from coronary artery bypass surgery.

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Effect of the Hexane Extract of Saussurea lappa on the Growth of HT-29 Human Colon Cancer Cells (목향 헥산추출물이 대장암세포인 HT-29 세포의 증식에 미치는 영향)

  • Kim, Eun-Ji;Park, Hee-Sook;Lim, Soon-Sung;Kim, Jong-Sang;Shin, Hyun-Kyung;Yoon, Jung-Han
    • Korean Journal of Food Science and Technology
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    • v.40 no.2
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    • pp.207-214
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    • 2008
  • In Asia Saussurea lappa (SL) has been used as a traditional herbal medicine to treat abdominal pain and tenesmus. Recently, in vitro cell culture studies have shown that SL has anti-ulcer, anti-inflammatory, and anti-tumor properties. To explore its potential chemopreventive and chemotherapeutic effects in colon cancer, we examined whether the hexane extract of SL (HESL) could inhibit the growth of HT-29 human colon cancer cells, and investigated the mechanisms for this effect. The cells were cultured with various concentrations (0-5 ${\mu}g/mL$) of HESL. The results indicated that HESL markedly decreased the numbers of viable HT-29 cells; whereas at the concentration of 5 ${\mu}g/mL$, HESL slightly decreased the viable cell numbers of CCD 1108Sk human skin normal fibroblasts at 72 hr. HESL substantially increased the numbers of cells in the sub G1 phase, and dose-dependently increased apoptotic cell numbers. Western blot analysis of the total cell lysates revealed that HESL increased Bax protein levels, but did not affect Bcl-2 levels. HESL induced the cleavage of poly (ADP-ribose) polymerase and caspases 8, 9, 7, and 3. This study demonstrated that HESL inhibits cell growth and induces apoptosis in HT-29 cells, which may be mediated by its ability to increase Bax levels and activate the caspase pathway. These findings may lead to the development of new therapeutic strategies for colon cancer treatment.

Effect of Fish Oil Ingestion on Serum Apoprotein and Platelet Function in Healthy Young Females (어유의 섭취가 젊은 여성의 혈청 Apoprotein 및 혈소판 기능에 미치는 영향)

  • 장현숙
    • Journal of Nutrition and Health
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    • v.23 no.3
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    • pp.157-169
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    • 1990
  • This study was designed to investigate the effect of supplementation of fish oil on serum apoprotein and platelet function in healthy young females. Eighteen female college students were divided into 3 groups. Each group fed a typical Korean diet supplemented with 15g, 12g, and 9g of fish oil respectively for 1-week. Blood samples were obtained 4 times, before supplementation, immediately after, 1-week after and 3-week after stopping supplementation. After 6-week break, the doses of fish oil were interchanged among 3 groups and the experiment was repeated to reduce interindividual variation. The concentration of apoprotein A, apoprotein B in the serum samples and the platelet adhesion, the platelet aggregation and bleeding time were determined immediately after supplementation of fish oil, 1-week after and 3-week after stopping supplementation and then the value compared with those of before supplementation period. The results obtained are summarized as follows: Serum apoprotein A levels decreased significantly(p<0.05), immediately after supplementation of fish oil in the 15g group. The serum apoprotein B levels did not show significant change. The platelet adhesion decreased significantly(p<0.05) 1-week after supplementation of fish oil in the 15g group. The platelet aggregation decreased significantly(p<0.01) immedeately after supplementation of fish oil in the 15g group.

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Effects of Iron Overload during Pregnancy on Oxidative Stress in Maternal Rats (임신 쥐의 철 과잉섭취가 조직의 산화적 스트레스에 미치는 영향)

  • Park, Mi-Na;Lee, Yeon-Sook
    • Journal of Nutrition and Health
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    • v.44 no.1
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    • pp.5-15
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    • 2011
  • Although iron is an essential mineral, excess iron intake during pregnancy may increase oxidative stress in tissues. This study was conducted to investigate the effects of iron overload during pregnancy on iron status and oxidative stress in maternal rats. Ten week-old female Sprague-Dawley rats were mated with male rats. Non-pregnant (control) and pregnant rats were fed diets containing normal Fe (35 mg/kg diet), high Fe (350 mg/kg diet), or excess Fe (1,050 mg/kg diet) during pregnancy. Rats were sacrificed on pregnancy day 19. No significant difference in weight gain, diet intake, or litter size was observed according to iron intake levels. Furthermore, serum iron, hemoglobin, and hematocrit were not different among the rats administered the three levels of Fe both in the control and pregnant groups. However, the iron levels were lower in pregnant rats than those in the control. The liver and spleen iron contents increased significantly in the excess Fe group. An increase in liver ferritin levels with increasing iron intake was observed. Protein carbonyl content, as a marker of oxidative stress, increased significantly in liver with increasing iron intake but not malondialdehyde. Glutathione peroxidase activity in the liver of pregnant rats fed excess iron decreased significantly. Bcl-2 protein expression in the liver declined remarkably with increasing maternal iron intake in pregnant rats. Taken together, iron overload during pregnancy had little effect on hematology. However, the deposits of iron in the liver and the decline in antioxidant enzyme activity implied increased oxidative stress in tissues of the excess Fe group. These results suggest that excess iron intake during pregnancy increases oxidative stress in maternal tissues and may also affect fetal tissues.

Activation and Abnormalities of Cell Cycle Regulating Factor in Head and Neck Squamous Cell Carcinoma Cell Lines: Abnormal Expression of CDKN2 Gene in Laryngeal Squamous Cell Carcinoma (두경부 편평상피세포암 세포주에서 세포주기조절인자의 활성 및 이상 : 후두편평상피세포암에서 종양억제유전자 CDKN2 유전자의 발현이상)

  • Song, Si-Youn;Han, Tae-Hee;Bai, Chang-Hoon;Kim, Yong-Dae;Song, Kei-Won
    • Journal of Yeungnam Medical Science
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    • v.22 no.2
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    • pp.166-182
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    • 2005
  • Background: Cyclin-dependent kinase (CDK) inhibitors are family of molecules that regulate the cell cycle. The CDKN2, a CDK4 inhibitor, also called p16, has been implicated in human tumorigenesis. The CDKN2 inhibits the cyclin/CDK complexes which regulate the transition from G1 to S phase of cell cycle. There is a previous report that homozygous deletion of CDKN2 region on chromosome 9p21 was detected frequently in astrocytoma, glioma and osteosarcoma, less frequently in lung cancer, leukemia and ovarian cancer, but not detected in colon cancer and neuroblastoma. However, little is known about the relationship between CDKN2 and laryngeal cancer. Therefore this study was initiated to investigate the role of CDKN2 in human laryngeal squamous cell carcinoma development.1) Materials and methods: We used 5 human laryngeal carcinoma cell lines whether they have deletions or losses of CDKN2 gene expression by DNA-PCR or RT-PCR, respectively. We examined 8 fresh frozen human laryngeal cancer tissues to detect the loss of heterozygosity (LOH) of CDKN2. PCR was performed by using microsatellite markers of short arm of human chromosome 9 (D9S126, D9S144, D9S156, D9S161, D9S162, D9S166, D9S171, D9S200 and D9SIFNA). For informative cases, allelic loss was scored if the signal of one allele was significantly decreased in tumor DNA when compared to the same allele in normal DNA. Results: The CDKN2 DNA deletion was observed in 3 cell lines. The CDKN2 mRNA expression was observed in only one cell line, which was very weak. LOH was detected in 7 cases (87.5%). Conclusion: These results suggest that CDKN2 plays a role in the carcinogenesis of human laryngeal squamous cell carcinoma.

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Emodin Studies on Anti-inflammatory and Skin Barrier Improvement Activities (Emodin의 항염 및 피부장벽개선 활성 연구)

  • Kim, Se-Gie;Choi, Jae Gurn;Jang, Young-Ah
    • Journal of the Korean Applied Science and Technology
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    • v.38 no.6
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    • pp.1383-1392
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    • 2021
  • It has been reported that emodin, a major pharmacologically active ingredient of herbal medicines such as Polygonum cuspidatum, Polygonum multiflorum, Rheum palmatum, and Aloe vera, is effective in antioxidant, antibacterial, anti-inflammatory, anticancer, and liver protection. In this study, to investigate the potential of emodin to be used as a skin disease and functional material, the activity related to the improvement of inflammation and skin barrier function was confirmed. To observe the anti-inflammatory effect on HaCaT cells, which are human keratinocytes, cytokine inhibition was confirmed by ELISA kit and protein expression by western blot. In HaCaT cells activated with TNF-α (10 ng/mL)/IFN-γ (10 ng/mL), emodin was treated with each concentration (5, 10, 20, 40) µM. As a result, It was confirmed that the production amount of TNF-α, IL-1β and IL-6 decreased as the concentration of emodin increased. In the experimental results on the expression levels of inflammation-related proteins iNOS and COX-2, it was confirmed that 48% of iNOS and 29% of COX-2 were inhibited compared to control at a concentration of 20 µM of emodin. As an indicator of skin barrier function improvement, the mRNA expression level of filaggrin, involucrin, and loricirn and the production amount of filaggrin, involucrin, and loricirn were confirmed. and excellent results were obtained with an emodin concentration-dependent increase. In particular, filaggrin, which was produced twice as much as the control at a concentration of 20 µM, is a protein involved in the formation of NMF, a natural moisturizing factor, and is known to play an important role in moisturizing the stratum corneum. In conclusion, it was confirmed that emodin can be used as a material for improving inflammation and improving skin barrier function, which is part of the potential for use as a skin disease and functional material. It is believed that if additional research is performed in the future, the scope of its application can be further expanded.