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Raw Inonotus obliquus polysaccharide counteracts Alzheimer's disease in a transgenic mouse model by activating the ubiquitin-proteosome system

  • Shumin Wang;Kaiye Dong;Ji Zhang;Chaochao Chen;Hongyan Shuai;Xin Yu
    • Nutrition Research and Practice
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    • 제17권6호
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    • pp.1128-1142
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    • 2023
  • BACKGROUND/OBJECTIVES: Inonotus obliquus has been used as antidiabetic herb around the world, especially in the Russian and Scandinavian countries. Diabetes is widely believed to be a key factor in Alzheimer's disease (AD), which is widely considered to be type III diabetes. To investigate whether I. obliquus can also ameliorate AD, it would be interesting to identify new clues for AD treatment. We tested the anti-AD effects of raw Inonotus obliquus polysaccharide (IOP) in a mouse model of AD (3×Tg-AD transgenic mice). MATERIALS/METHODS: SPF-grade 3×Tg-AD mice were randomly divided into three groups (Control, Metformin, and raw IOP groups, n = 5 per group). β-Amyloid deposition in the brain was analyzed using immunohistochemistry for AD characterization. Gene and protein expression of pertinent factors of the ubiquitin-proteasome system (UPS) was determined using real-time quantitative polymerase chain reaction and Western blotting. RESULTS: Raw IOP significantly reduced the accumulation of amyloid aggregates and facilitated UPS activity, resulting in a significant reduction in AD-related symptoms in an AD mouse model. The presence of raw IOP significantly enhanced the expression of ubiquitin, E1, and Parkin (E3) at both the mRNA and protein levels in the mouse hippocampus. The mRNA level of ubiquitin carboxyl-terminal hydrolase isozyme L1, a key factor involved in UPS activation, also increased by approximately 50%. CONCLUSIONS: Raw IOP could contribute to AD amelioration via the UPS pathway, which could be considered as a new potential strategy for AD treatment, although we could not exclude other mechanisms involved in counteracting AD processing.

아토피성 피부염병변에 치료효과가 있는 천연염료 연구(II) - 솔잎 추출물 - (A Study on Natural Dye Having the Effects on the Atopic Dermatitis (Part II) - Pine Needles Extract -)

  • 이정순;우효정
    • 한국염색가공학회지
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    • 제24권3호
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    • pp.196-203
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    • 2012
  • The purpose of this study was to investigate usefulness of the pine needles extract on Atopic Dermatitis(AD)-like skin lesions. To investigate the effect of pine needles extract in vivo, atopic dermatitis (NC/Nga) mice using DNCB (2.4-Dinitrochlorbenzene) was used. NC/Nga mice were challenged with DNCB during 2 weeks to develope AD-like skin lesion. After that, pine needles extract was applied to AD-like skin lesion on the backs of the NC/Nga mice during 3 weeks. The efficacy of pine needles extract in the NC/Nga mice was evaluated by measurement of the skin lesion severity(NC mouse score), the serum IgE level, epidermal thickness changes, and mast cell number. Blood was collected from the retro-orbital area and the level of IgE in the blood was measured. The epidermal thickness and mast cell number were observed by microscopic method after H&E stain. The serum IgE levels were decreased after treatment with pine needles extract. The epidermal thickness and mast cell number were decreased after treatment with pine needles extract. To conclude, the topical application of pine needles extract suppressed the progression of AD-like skin lesion.

아토피 피부염 환자에 대한 임상적 연구; 한의학적인 임상유형분류 및 치료 (Clinical Study of Atopic Dermatitis ; the Classification of Oriental Medical Clinical type and Treatment)

  • 윤화정;고우신
    • 대한한의학회지
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    • 제22권2호
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    • pp.10-21
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    • 2001
  • Objectives : Atopic dermatitis(AD) assume an remarkable clinical aspect and it s diagnosis almost depends on clinical symptoms. Therefore, we aimed to study the clinical diagnostic standard of AD for more accurate treatment. We repert as follows; Methods : For 6 months from March to August in 2000 we selected fifty outpatients who were prognosis of AD in the department of dermatology, Oriental medical hospitol, Dong-eui University. Results and Conclusions : 1. We classified of the grade, the condition of AD patient was slight and severe, by the sum of total by the clinical index of AD (diagnostic features). 2. By consulting previous oriental medical theories, we divided symptom-complex of AD into two type ; one was damp-heat type and the other was deficiency of blood- wind-dryness type. 3. Male to female ratio was 17 : 33 and the third stage, more than half of the patients were adolescents. 4. According to the results of symptom-complex of AD patients, on the first examination damp-heat type was more than deficiency of blood-wind-dryness type and in progressing treatment, the condition has been change to deficiency of blood-wind-dryness type. 5. In the lesions of AD, arm and knee were most serious skin lesions and in symptoms of AD, pruritus was most complained, and in progressing treatment, erosion and erythema were greatly improved. 6. When we measured the levels of serum Total IgE, that of thirty eight patientswere higher than that of normal, but elevation of serum IgE levels was not correlated with the severity of AD.

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e-Marketplace에서의 비교도전에 의한 광고계획 모델 (Ad Planning Model by Comparison Challenge Approach in the e-Marketplace)

  • 이재규;이재원
    • 지능정보연구
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    • 제9권3호
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    • pp.137-153
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    • 2003
  • 비교구매는 e-Marketplace의 매출에 큰 영향력을 미치고 있으나 운영 수익은 대부분 광고에 의존한다. 하지만 인터넷 광고의 수익률은 열악한 상태이며, 종량제 기반 광고 방법의 확대로 소비자에게 덜 알려진 판매자의 제품정보 노출 기회는 더욱 줄어들고 있다. 따라서 비교구매 사업자의 광고 수익을 높이면서 판매자 입장에서는 예산 및 제약 조건 범위 내에서 광고 노출의 효율성을 최적화하는 방법 및 시스템에 대한 연구가 필요하다. 본 연구에서는 비교도전을 이용한 비교광고 방법을 제안하고 그 실행 방법으로 판매자의 비교도전 계획 모델을 사용하는 e-Marketplace기반 비교구매 사업자의 비교광고 시스템을 설계하고 구현하였다. 비교도전 계획 모델은 경쟁사(Competitor), 경쟁 제품(product) 그리고 제품의 사양(Specification)에 대한 수준별 도전 정책을 적용하며, 양 사의 제품 사양 속성 값들간의 기능적 거리를 양적 수치화 하여 판매자 제품이 경쟁사 제품에 가장 유사하지만 우세한(Similar but Superior) 쌍들에 대한 비교광고 포트폴리오를 구성함을 목적으로 한다. 비교도전 계획 시스템은 비교가치의 생성과 최적화의 단계로 이뤄진다. 주요 5개 PC제조사의 데스크탑 제품자료를 사용하여 프로토타입을 구축하였으며, 타 비교광고 방법과 대비한 성능 평가를 수행하였다. 또한 e-Marketplace기반 비교구매 사업자의 비교도전에 의한 비교광고 표시 방법을 예시하였다.

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The Importance of Food Open Challenge Test in Atopic Dermatitis: The Comparison of Allergy History, Skin-Prick Test, and Specific IgE Detection

  • Noh, Geun-Woong;Ji, Eun-Jung;Park, Jung-Nan;Kim, Kyung-Hee;Do, Min-Hee;Lee, Eung-Kyung;Lee, Sang-Sun
    • Nutritional Sciences
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    • 제2권2호
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    • pp.119-124
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    • 1999
  • Food allergies play an important role in Atopic Dermatitis (AD). Dietary manipulation is essential in the management of AD. However, there has been a paucity of data reporting the prevalence of food allergies in AD patients in Korea. In this study, the Food Open Challenge Tests (FOCT) were conducted to investigate food allergies in AD patients. The skin-prick test and the detection of specific IgE, as well as allergy history of patient were used to detect food allergies in all AD patients. Elimination diet was conducted for two weeks prior to FOCTs. The prevalence of food allergies by FOCT is as follows: milk (67.3%); chicken (64.2%); pork (62.8%); eggs (61.0%); beef(55.4%) ; wheat (52.0%) and soybean (45.2%). Allergenic food items in Korean AD patients were different from people in other foreign countries. The seven major foods those tested positively by FOCTs were completely eliminated from the replaced diets for two weeks, and were subsequently reintroduced one at a time. Results from FOCTs were not comparable with allergy history or skin-prick tests or specific IgE detection. The sensitivity and specificity of skin-prick tests and specific IgE detection were lower than FOCTs. Allergy history, skin-prick tests, and specific IgE detection are useful for the identification of food allergen but its clinical significance differed according to food items. Therefore, we conclude that even though a 10-day delay was necessary after food challenge, FOCT is a useful and valid method to confirm food allergies and may be essential for the effective control of food allergies for treatment of AD.

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Diosmetin and Its Glycoside, Diosmin, Improve Atopic Dermatitis-Like Lesions in 2,4-Dinitrochlorobenzene-Induced Murine Models

  • Park, Sang-a;Bong, Sim-Kyu;Lee, Jin Woo;Park, No-June;Choi, Yongsoo;Kim, Sang Moo;Yang, Min Hye;Kim, Yong Kee;Kim, Su-Nam
    • Biomolecules & Therapeutics
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    • 제28권6호
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    • pp.542-548
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    • 2020
  • Naturally derived diosmetin and its glycoside diosmin are known to be effective in treating inflammatory disease. This study was performed to determine whether diosmin and diosmetin have the effect of improving atopic dermatitis in a 2,4-dinitrochlorobenzen (DNCB)-induced atopic dermatitis (AD) model. DNCB was used to establish AD model in hairless mice. Skin moisture, serum immunoglobulin E (IgE), interleukin 4 (IL-4), and histological analysis were performed to measure the effectiveness of diosmin and diosmetine to improve AD. IL-4 levels were also measured in RBL-2H3 cells. Administration of diosmetin or diosmin orally inhibited the progress of DNCB-induced AD-like lesions in murine models by inhibiting transdermal water loss (TEWL) and increasing skin hydration. Diosmetin or diosmin treatment also reduced IgE and IL-4 levels in AD-induced hairless mouse serum samples. However, in the in vitro assay, only diosmetin, not diosmin, reduced the expression level of IL-4 mRNA in RBL-2H3 cells. Diosmin and diosmetine alleviated the altered epidermal thickness and immune cell infiltration in AD. Diosmin is considered effective in the cure of AD and skin inflammatory diseases by being converted into diosmetin in the body by pharmacokinetic metabolism. Thus, oral administration of diosmetin and diosmin might be a useful agent for the treatment of AD and cutaneous inflammatory diseases.

Tryptophan-derived Alkaloids from Hedera rhombea Fruits and Their Butyrylcholinesterase Inhibitory Activity

  • Ha, Manh Tuan;Park, Se Eun;Kim, Jeong Ah;Woo, Mi Hee;Choi, Jae Sue;Min, Byung Sun
    • Natural Product Sciences
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    • 제28권3호
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    • pp.138-142
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    • 2022
  • Alzheimer's disease (AD) is the most common age-related neurodegenerative disease in industrialized countries. It is estimated that about 47 million people living with dementia and the number of cases will be tripled by 2050. However, the exact mechanism of AD is not known, and full therapy has still not been found. Various tryptophan-derived alkaloids have been reported as promising agents for the treatment of AD. In the present study, a series of tryptophan-derived alkaloids were isolated and characterized from the methanol extract of Hedera rhombea fruit. Based on the analysis of their observed and reported spectroscopic data, their structures were identified as N-[4'-hydroxy-(E)-cinnamoyl]-L-tryptophan (1), N-[3',4'-dihydroxy-(E)-cinnamoyl]-L-tryptophan (2), N-[4'-hydroxy-(E)-cinnamoyl]-L-tryptophan methyl ester (3), and N-[3',4'-dihydroxy-(E)-cinnamoyl]-L-tryptophan methyl ester (4). These compounds were screened for anti-Alzheimer activity via their inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes in vitro. As a result, compounds 3 and 4 showed moderate BChE inhibition with IC50 values of 86.9 and 78.4 μM, respectively, compared to those of the positive control [berberine (IC50 = 11.5 μM)]. However, all four compounds did not show significant inhibition of the AChE enzyme. This is the first time, the AChE and BChE inhibitory activities of these tryptophan-derived alkaloids were investigated and reported.

라벤더와 백리향 혼합오일이 아토피피부염 생쥐의 산화적 스트레스, 면역, 피부상태에 미치는 효과 (Effects of Blending Oil of Lavender and Thyme on Oxidative Stress, Immunity, and Skin Condition in Atopic Dermatitis Induced Mice)

  • 서영미;정석희
    • 대한간호학회지
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    • 제45권3호
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    • pp.367-377
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    • 2015
  • Purpose: The purpose of this study was to evaluate the effects of essential oil on oxidative stress, immunity, and skin condition in atopic dermatitis (AD) induced mice. Methods: This study was a $3{\times}3$ factorial design. Factors were oil type (Lavender, Thyme, and 2:1 mixture of lavender and thyme oil [blending oil]) and treatment period (0 day, 7 days, and 21 days). The samples were 45 mice with AD and randomly assigned to nine groups of five mice per group. The dependent variables such as superoxide radical, IgE, degranulated mast cells, and epidermal thickness were measured. Data were collected from February to April in 2014. Descriptive statistics, One-way ANOVA, Two-way ANOVA, and Tukey's HSD test were performed using the SPSS WIN 20.0 program. Results: Dependent variables were not statistically significantly different by the three oil types (p >.05). Essential oils such as lavender, thyme, and blending oil were all effective in reducing AD symptoms and especially 2:1 blending oil were most effective. There were statistically significant differences by the three treatment periods in all dependent variables (p <.001). There were statistically significant interactions between oil types and treatment periods in all dependent variables (p <.01). For decreasing superoxide radical, degranulated mast cells, and epidermal thickness, 2:1 mixed oil should be applied for at least 21 days. Otherwise to reduce IgE, 2:1 mixed oil should be used for at least 7 days. Conclusion: These findings provide bases for developing effective interventions for AD patients to manage their AD symptoms.

The regulatory effect of AST cream on atopic dermatitis-like skin disease.

  • Han, Na-Ra;Kim, Hyung-Min;Jeong, Hyun-Ja
    • 셀메드
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    • 제9권3호
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    • pp.7.1-7.4
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    • 2019
  • In this study, we investigated an inhibitory effect of AST cream on atopic dermatitis (AD) using a 2,4-dinitrochlorobenzene-induced AD murine model. Topical treatment with AST cream ameliorated the severity of AD-like lesional skin through decreases in infiltration of inflammatory cells and time of scratching behaviors. Also, AST cream reduced histamine and IgE levels in serum. The protein levels of IL-4 and IL-6 in AD-like lesional skin were suppressed by AST cream. These findings suggest that AST cream would be an alternative therapeutic agent for AD-like skin diseases.

아토피성 피부염병변에 치료효과가 있는 천연염료 연구(I) - 대나무 추출물 - (A Study on Natural Dye Having the Effects on the Atopic Dermatitis (Part I ) - Bamboo Extract -)

  • 이정순;정고은
    • 한국염색가공학회지
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    • 제24권3호
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    • pp.189-195
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    • 2012
  • The purpose of this study was to investigate the possibility of bamboo extract as natural dye having the effect on atopic dermatitis(AD). To investigate the effect of bamboo extract on AD in vivo, we applied bamboo extract to the AD-like skin lesion the backs of atopic of NC/Nga mice, an animal model of AD. NC/Nga mice were challenged with DNCB(2.4-Dinitrochlorbenzene) to develope AD-like skin lesions. The efficacy of bamboo extract in the NC/Nga mice was evaluated by measurement of the skin lesion severity(NC mouse score), the serum IgE level, epidermal thickness changes, and mast cell number. Bamboo extracts improved skin lesions in NC/Nga mice. The serum IgE levels were decreased after treatment with bamboo extract. Histological examinations revealed a decrease in epidermal thickness and mast cell number after treatment with bamboo extract. To conclude, the topical application of bamboo extract suppressed the progression of AD-like skin lesions.