Park Ju Ho, Choi Ji Yeon, Son Dong Ju, Park Eun Kyung, Song Min Jong, Hellström Mats, Hong Jin Tae
College of Pharmacy and Medical Research Center, Chungbuk National University, 194-31 Osongsaengmyeong 1-ro, Osong-eup, Heungduk-gu, Cheongju 361-951, Korea.
Department of Obstetrics & Gynecology, Daejeon St. Mary's Hospital, The Catholic University of Korea, 64 Daeheung-Ro (Daeheung-dong), Jung-gu, Daejeon 301-723, Korea.
Int J Mol Sci. 2017 Mar 30;18(4):738. doi: 10.3390/ijms18040738.
has potent antioxidant and anti-inflammatory properties. However, its anti-dermatitic effect has not yet been reported. In this study, we investigated the anti-dermatitic effects of titrated extract of Centella asiatica (TECA) in a phthalic anhydride (PA)-induced atopic dermatitis (AD) animal model as well as in vitro model. An AD-like lesion was induced by the topical application of five percent PA to the dorsal skin or ear of Hos:HR-1 mouse. After AD induction, 100 μL of 0.2% and 0.4% of TECA (40 μg or 80 μg/cm²) was spread on the dorsum of the ear or back skin three times a week for four weeks. We evaluated dermatitis severity, histopathological changes and changes in protein expression by Western blotting for inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and NF-κB activity, which were determined by electromobility shift assay (EMSA). We also measured TNF-α, IL-1β, IL-6, and IgE concentration in the blood of AD mice by enzyme-linked immunosorbent assay (ELISA). TECA treatment attenuated the development of PA-induced atopic dermatitis. Histological analysis showed that TECA inhibited hyperkeratosis, mast cells and infiltration of inflammatory cells. TECA treatment inhibited expression of iNOS and COX-2, and NF-κB activity as well as the release of TNF-α, IL-1β, IL-6, and IgE. In addition, TECA (1, 2, 5 μg/mL) potently inhibited Lipopolysaccharide (LPS) (1 μg/mL)-induced NO production, expression of iNOS and COX-2, and NF-κB DNA binding activities in RAW264.7 macrophage cells. Our data demonstrated that TECA could be a promising agent for AD by inhibition of NF-κB signaling.
具有强大的抗氧化和抗炎特性。然而,其抗皮炎作用尚未见报道。在本研究中,我们研究了积雪草滴定提取物(TECA)在邻苯二甲酸酐(PA)诱导的特应性皮炎(AD)动物模型以及体外模型中的抗皮炎作用。通过将5%的PA局部涂抹于Hos:HR-1小鼠的背部皮肤或耳部来诱导类似AD的损伤。AD诱导后,每周三次将100μL的0.2%和0.4%的TECA(40μg或80μg/cm²)涂抹于耳背或背部皮肤,持续四周。我们通过蛋白质免疫印迹法评估皮炎严重程度、组织病理学变化以及诱导型一氧化氮合酶(iNOS)、环氧化酶-2(COX-2)和NF-κB活性的蛋白质表达变化,通过电泳迁移率变动分析(EMSA)来测定NF-κB活性。我们还通过酶联免疫吸附测定(ELISA)测量AD小鼠血液中TNF-α、IL-1β、IL-6和IgE的浓度。TECA治疗减轻了PA诱导的特应性皮炎的发展。组织学分析表明,TECA抑制了角化过度、肥大细胞和炎性细胞浸润。TECA治疗抑制了iNOS和COX-2的表达、NF-κB活性以及TNF-α、IL-1β、IL-6和IgE的释放。此外,TECA(1、2、5μg/mL)在RAW264.7巨噬细胞中有效抑制脂多糖(LPS)(1μg/mL)诱导的NO产生、iNOS和COX-2的表达以及NF-κB DNA结合活性。我们的数据表明,TECA通过抑制NF-κB信号通路可能成为治疗AD的有前景的药物。