Gao Qing, Peng Jun, Xiong Meng, Zhou Shunhua, Wang Xiaojuan, Lu Jing, Guo Yuanyi, Peng Qinghua, Zeng Meiyan, Song Houpan
Hunan Provincial Key Laboratory of Traditional Chinese Medicine Diagnostics, Hunan University of Chinese Medicine, Changsha, Hunan Province, China; School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan Province, China.
The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, China.
Eur J Pharmacol. 2025 Jun 5;996:177571. doi: 10.1016/j.ejphar.2025.177571. Epub 2025 Apr 1.
Uveitis is an inflammatory ocular condition characterized by an autoimmune etiology. Sinomenine (SIN), the main active constituent of the rhizome of Sinomenium acutum (Thunb.) Rehd. et Wils., exhibits both anti-inflammatory and immunosuppressive properties. The present study sought to investigate the therapeutic effects of SIN on experimental autoimmune uveitis (EAU) in rats and to elucidate its underlying mechanisms. A bioinformatics analysis was conducted to identify signaling pathways implicated in the pathogenesis of uveitis, leading to the identification of the PI3K/AKT and NF-κB pathways for further experimental validation. An EAU model was subsequently established, and the ocular surface morphology was examined using slit lamp microscopy and hematoxylin-eosin staining. Immunofluorescence was utilized to measure the protein expression and distribution. Enzyme-linked immunosorbent assay was used to determine the expression of inflammatory cytokines. Experimental findings demonstrated that SIN significantly decreased ocular inflammation scores. Further validation revealed that SIN significantly elevated levels of interleukin-10 (IL-10) while reducing levels of IL-17, tumor necrosis factor-α (TNF-α), and IL-1β in EAU rats. SIN significantly suppressed the expression of phosphorylated proteins in the PI3K/AKT and NF-κB pathways. In addition, it reduced the expression of RORγt while enhancing the expression of Foxp3, the transcription factors associated with Th17 cells and Tregs, respectively. In summary, our data demonstrate that SIN alleviates EAU inflammation by inhibiting the activation of the PI3K/AKT and NF-κB signaling pathways and restoring the balance between Th17 and Tregs. These findings highlight SIN as a promising therapeutic agent for the treatment of uveitis.
葡萄膜炎是一种以自身免疫病因学为特征的眼部炎症性疾病。青藤碱（SIN）是青风藤根茎的主要活性成分，具有抗炎和免疫抑制特性。本研究旨在探讨青藤碱对大鼠实验性自身免疫性葡萄膜炎（EAU）的治疗作用，并阐明其潜在机制。进行了生物信息学分析以确定与葡萄膜炎发病机制相关的信号通路，从而确定PI3K/AKT和NF-κB通路以进行进一步的实验验证。随后建立了EAU模型，并使用裂隙灯显微镜和苏木精-伊红染色检查眼表形态。利用免疫荧光法测量蛋白质表达和分布。采用酶联免疫吸附测定法测定炎症细胞因子的表达。实验结果表明，青藤碱显著降低了眼部炎症评分。进一步验证表明，青藤碱显著提高了EAU大鼠白细胞介素-10（IL-10）的水平，同时降低了IL-17、肿瘤坏死因子-α（TNF-α）和IL-1β的水平。青藤碱显著抑制了PI3K/AKT和NF-κB通路中磷酸化蛋白的表达。此外，它降低了RORγt的表达，同时增强了分别与Th17细胞和调节性T细胞（Tregs）相关的转录因子Foxp3的表达。总之，我们的数据表明，青藤碱通过抑制PI3K/AKT和NF-κB信号通路的激活以及恢复Th17和Tregs之间的平衡来减轻EAU炎症。这些发现突出了青藤碱作为治疗葡萄膜炎的一种有前景的治疗药物。
