Tian Xuyan, Tang Lipeng, Wei Fengjiao, Chen Huanpeng, Sheng Longxiang, Yang Yuying, Zhou Xiaoqing, Li Yongchao, Xu Xiaoting, Zhang Boyang, Liu Zhonghua, Lei Yu, Yu Bolan, Bai Chuan, He Xixin, Huang Zhaofeng
Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China; Key Laboratory of Tropical Disease Control (Sun Yat-Sen University), Ministry of Education, Guangzhou, China.
Department of Pharmacology of Traditional Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
Mol Immunol. 2021 Apr;132:30-40. doi: 10.1016/j.molimm.2021.01.019. Epub 2021 Feb 2.
Psoriasis is a refractory inflammatory skin disease affecting 2 %-3 % of the world population, characterized by the infiltration and hyper-proliferation of inflammatory cells and aberrant differentiation of keratinocytes. Targeting the IL-23/ Th17 axis has been well recognized as a promising therapeutic strategy, as the IL-23/ Th17 signal plays a vital role in the pathology of psoriasis. Three pentacyclic triterpene compounds isolated from loquat leaves have been reported with significant inhibitory effects on RORγt transcription activity and Th17 cell differentiation, and excellent performance in preventing lupus nephritis pathogenesis. However, the potential effects of these pentacyclic triterpene compounds on psoriasis remain unknown. In this study, we demonstrated the potent therapeutic effects of these pentacyclic triterpene compounds on psoriasis. These three pentacyclic triterpene compounds significantly alleviated skin inflammation as well as aberrant keratinocyte proliferation in an imiquimod-induced mouse psoriasis model. These compounds also inhibited the infiltration of immune cells and the level of pro-inflammatory cytokine in the dermis, as well as the cells number and changed the cytokine profiling expression of Th17 cells. These compounds could reduce the amount of CD4 and CD8 T cells in local lymph node, but not in spleen, which is different from hydrocortisone, the positive control treatment. These results suggest better performance of these compounds than steroids on treating psoriasis with less side effects on the integrated immune system. In summary, our findings uncover the potent therapeutic effects of pentacyclic triterpene compounds on psoriasis, providing potential candidate compounds for drug development.
银屑病是一种难治性炎症性皮肤病，影响着全球2%-3%的人口，其特征为炎症细胞浸润、过度增殖以及角质形成细胞的异常分化。靶向白细胞介素-23/辅助性T细胞17（IL-23/Th17）轴已被公认为一种有前景的治疗策略，因为IL-23/Th17信号在银屑病的病理过程中起着至关重要的作用。据报道，从枇杷叶中分离出的三种五环三萜化合物对维甲酸相关孤儿受体γt（RORγt）转录活性和Th17细胞分化具有显著抑制作用，并且在预防狼疮性肾炎发病机制方面表现出色。然而，这些五环三萜化合物对银屑病的潜在影响尚不清楚。在本研究中，我们证明了这些五环三萜化合物对银屑病具有显著的治疗效果。在咪喹莫特诱导的小鼠银屑病模型中，这三种五环三萜化合物显著减轻了皮肤炎症以及角质形成细胞的异常增殖。这些化合物还抑制了免疫细胞在真皮中的浸润和促炎细胞因子水平，以及Th17细胞的数量并改变了其细胞因子谱表达。这些化合物可以减少局部淋巴结中CD4和CD8 T细胞的数量，但不会减少脾脏中的数量，这与阳性对照药物氢化可的松不同。这些结果表明，这些化合物在治疗银屑病方面比类固醇具有更好的效果，并且对整体免疫系统的副作用更小。总之，我们的研究结果揭示了五环三萜化合物对银屑病的显著治疗效果，为药物开发提供了潜在的候选化合物。
