Liu Bin, Peng Yuan, Wang Congling, Wei Huixia, Xu Shuqin, Liu Yunfeng, Yin Xuewei, Bi Hongsheng, Guo Dadong
Shandong University of Traditional Chinese Medicine, No. 4655#, Daxue Road, Jinan, 250355, China.
Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250002, China.
Sci Rep. 2025 May 12;15(1):16424. doi: 10.1038/s41598-025-01286-7.
Uveitis is a series of autoimmune eye diseases that can seriously damage people's eyesight. This study aimed to explore the therapeutic potential of baicalin in treating uveitis, focusing on its modulation of HIF-1α expression and macrophage polarization. Using an experimental autoimmune uveitis (EAU) rat model, we found that baicalin can significantly reduce fundus inflammation in EAU rats. Spectral-domain optical coherence tomography revealed retinal vascular thickening in the EAU group, indicating severe inflammation, which baicalin effectively mitigated. Histopathological analysis confirmed reduced inflammatory cell infiltration in the ciliary body and retina. Co-immunoprecipitation analyses showed that HIF-1αinteracted with macrophage-related factors, including iNOS and ARG1. Baicalin downregulated HIF-1α and iNOS while upregulating ARG1, balancing pro-inflammatory M1 and anti-inflammatory M2 macrophage polarization. Flow cytometry demonstrated a reversal of M1/M2 macrophage ratios in the EAU group after baicalin treatment. Additionally, baicalin improved macrophage mitochondrial membrane potential and decreased reactive oxygen species (ROS) levels, shifting macrophage polarization toward an anti-inflammatory state. These findings confirm that baicalin can effectively reduce inflammation and restore immune balance by orchestrating the HIF-1α pathway, establishing a promising therapeutic candidate for uveitis and highlighting the potential of natural bioactive compounds in treating and preventing inflammatory diseases through targeted immune modulation.
葡萄膜炎是一系列自身免疫性眼病，可严重损害人的视力。本研究旨在探讨黄芩苷治疗葡萄膜炎的潜在疗效，重点关注其对缺氧诱导因子-1α（HIF-1α）表达和巨噬细胞极化的调节作用。利用实验性自身免疫性葡萄膜炎（EAU）大鼠模型，我们发现黄芩苷可显著减轻EAU大鼠的眼底炎症。频域光学相干断层扫描显示EAU组视网膜血管增厚，表明存在严重炎症，而黄芩苷可有效减轻这种炎症。组织病理学分析证实睫状体和视网膜中的炎性细胞浸润减少。免疫共沉淀分析表明，HIF-1α与包括诱导型一氧化氮合酶（iNOS）和精氨酸酶1（ARG1）在内的巨噬细胞相关因子相互作用。黄芩苷下调HIF-1α和iNOS，同时上调ARG1，平衡促炎性M1和抗炎性M2巨噬细胞极化。流式细胞术显示黄芩苷治疗后EAU组M1/M2巨噬细胞比例发生逆转。此外，黄芩苷改善了巨噬细胞线粒体膜电位并降低了活性氧（ROS）水平，使巨噬细胞极化向抗炎状态转变。这些发现证实黄芩苷可通过调控HIF-1α途径有效减轻炎症并恢复免疫平衡，为葡萄膜炎建立了一种有前景的治疗候选药物，并突出了天然生物活性化合物通过靶向免疫调节治疗和预防炎症性疾病的潜力。
