Wen Jiaolin, Pei Heying, Wang Xianhuo, Xie Caifeng, Li Shucai, Huang Li, Qiu Neng, Wang Wenwen, Cheng Xia, Chen Lijuan
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
J Dermatol Sci. 2014 Jun;74(3):242-50. doi: 10.1016/j.jdermsci.2014.03.001. Epub 2014 Mar 15.
Psoriasis is a chronic T cell-mediated inflammatory skin disease. Studies have shown that angiogenesis plays an important role in the pathogenesis of psoriasis. Studies have also indicated that Gambogic acid (GA) inhibits angiogenesis and may be a viable drug candidate in anti-angiogenesis therapies.
The aim of this study was to investigate the anti-psoriatic effect of GA and the possible mechanisms.
MTT test on HaCaT cells and immunofluorescence on HUVEC cells were processed. An O/W cream of GA was prepared and topically applied to the ears of K14-VEGF transgenic mice and psoriasis-like guinea-pigs, and the tail skin of Balb/C mice independently. Furthermore, hematoxylin-eosin staining of tissues from three models and immunohistochemistry staining of ear samples from K14-VEGF mice were performed.
In vitro, GA inhibited proliferation of HaCaTs and TNF-α-induced activation of NF-κB in HUVECs. In vivo, animals treated with GA showed significant morphological and histological improvements. Immunohistochemical analysis of K14-VEGF transgenic mice revealed that hyperplastic and inflamed vessels were suppressed with GA treatment. The expression of adhesion molecules such as ICAM-1 and E-selectin was significantly decreased. GA inhibited angiogenesis and the expression of VEGFR2 and p-VEGFR2. T lymphocyte infiltration and the expression of IL-17 and IL-22 were also reduced by GA treatment.
Our results suggest that GA has anti-psoriatic efficacy through inhibition of angiogenesis and inflammation. Therefore, GA is attractive and offers future potential for application in patients with psoriasis.
银屑病是一种慢性T细胞介导的炎症性皮肤病。研究表明，血管生成在银屑病的发病机制中起重要作用。研究还表明，藤黄酸（GA）可抑制血管生成，可能是抗血管生成治疗中一种可行的候选药物。
本研究旨在探讨GA的抗银屑病作用及其可能机制。
对HaCaT细胞进行MTT试验，对人脐静脉内皮细胞（HUVEC）进行免疫荧光检测。制备GA的水包油乳膏，并分别局部应用于K14-VEGF转基因小鼠、银屑病样豚鼠的耳部以及Balb/C小鼠的尾部皮肤。此外，对三种模型的组织进行苏木精-伊红染色，对K14-VEGF小鼠的耳部样本进行免疫组织化学染色。
在体外，GA抑制HaCaT细胞的增殖以及HUVEC细胞中肿瘤坏死因子-α（TNF-α）诱导的核因子-κB（NF-κB）激活。在体内，用GA治疗的动物在形态和组织学上有显著改善。对K14-VEGF转基因小鼠的免疫组织化学分析显示，GA治疗可抑制增生和发炎的血管。细胞间黏附分子-1（ICAM-1）和E-选择素等黏附分子的表达显著降低。GA抑制血管生成以及血管内皮生长因子受体2（VEGFR2）和磷酸化VEGFR2（p-VEGFR2）的表达。GA治疗还减少了T淋巴细胞浸润以及白细胞介素-17（IL-17）和白细胞介素-22（IL-22）的表达。
我们的结果表明，GA通过抑制血管生成和炎症具有抗银屑病疗效。因此，GA具有吸引力，为银屑病患者的应用提供了未来潜力。
