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滴定提取物与虾青素在邻苯二甲酸酐诱导的特应性皮炎小鼠模型中的联合作用。

Combination Effect of Titrated Extract of and Astaxanthin in a Mouse Model of Phthalic Anhydride-Induced Atopic Dermatitis.

作者信息

Park Ju Ho, Yeo In Jun, Jang Jun Sung, Kim Ki Cheon, Park Mi Hee, Lee Hee Pom, Han Sang Bae, Hong Jin Tae

机构信息

College of Pharmacy and Medical Research Center, Chungbuk National University, Cheongju, Korea.

出版信息

Allergy Asthma Immunol Res. 2019 Jul;11(4):548-559. doi: 10.4168/aair.2019.11.4.548.

Abstract

PURPOSE

In our previous study, we demonstrated that both titrated extract of (TECA) and astaxanthin (AST) have anti-inflammatory effects in a 5% phthalic anhydride (PA) mouse model of atopic dermatitis (AD). The increasing prevalence of AD demands new therapeutic approaches for treating the disease. We investigated the therapeutic efficacy of the ointment form of TECA, AST and a TECA + AST combination in a mouse model of AD to see whether a combination of the reduced doses of 2 compounds could have a synergistic effect.

METHODS

An AD-like lesion was induced by the topical application of 5% PA to the dorsal ear and back skin of an Hos:HR-1 mouse. After AD induction, TECA (0.5%), AST (0.5%) and the TECA (0.25%) + AST (0.25%) combination ointment (20 μg/cm²) were spread on the dorsum of the ear or back skin 3 times a week for 4 weeks. We evaluated dermatitis severity, histopathological changes and changes in protein expression by Western blotting for inducible nitric oxide synthase (iNOS), cyclocxygenase (COX)-2, and nuclear factor (NF)-κB activity. We also measured the concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and immunoglobulin E (IgE) in the blood of AD mice by enzyme-linked immunosorbent assay (ELISA).

RESULTS

PA-induced skin morphological changes and ear thickness were significantly reduced by TECA, AST and TECA + AST treatments, but these inhibiting effects were more pronounced in the TECA + AST treatment. TECA, AST and the TECA+AST reatments inhibited the expression of iNOS and COX-2; NF-κB activity; and the release of TNF-α, IL-6 and IgE. However, the TECA+AST treatment showed additive or synergistic effects on AD.

CONCLUSIONS

Our results demonstrate that the combination of TECA and AST could be a promising therapeutic agent for AD by inhibiting NF-κB signaling.

摘要

目的

在我们之前的研究中,我们证明了滴定提取物(TECA)和虾青素(AST)在5%邻苯二甲酸酐(PA)诱导的特应性皮炎(AD)小鼠模型中均具有抗炎作用。AD患病率的不断上升需要新的治疗方法来治疗该疾病。我们研究了TECA、AST软膏形式以及TECA + AST组合在AD小鼠模型中的治疗效果,以观察两种化合物的低剂量组合是否具有协同作用。

方法

通过将5% PA局部涂抹于Hos:HR-1小鼠的背部耳朵和背部皮肤来诱导类似AD的病变。AD诱导后,将TECA(0.5%)、AST(0.5%)和TECA(0.25%)+ AST(0.25%)组合软膏(20μg/cm²)每周3次涂抹于耳背或背部皮肤,持续4周。我们通过蛋白质免疫印迹法评估了皮炎严重程度、组织病理学变化以及诱导型一氧化氮合酶(iNOS)、环氧化酶(COX)-2和核因子(NF)-κB活性的蛋白质表达变化。我们还通过酶联免疫吸附测定(ELISA)测量了AD小鼠血液中肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6和免疫球蛋白E(IgE)的浓度。

结果

TECA、AST和TECA + AST处理均显著减轻了PA诱导的皮肤形态变化和耳朵厚度,但这些抑制作用在TECA + AST处理中更为明显。TECA、AST和TECA + AST处理均抑制了iNOS和COX-2的表达;NF-κB活性;以及TNF-α、IL-6和IgE的释放。然而,TECA + AST处理对AD显示出相加或协同作用。

结论

我们的结果表明,TECA和AST的组合通过抑制NF-κB信号通路可能是一种有前景的AD治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c24/6557773/26b4e11470aa/aair-11-548-g001.jpg

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