2. Academic Validation
  3. Baicalin prevents experimental autoimmune uveitis by promoting macrophage polarization balance through inhibiting the HIF-1α signaling pathway

Baicalin prevents experimental autoimmune uveitis by promoting macrophage polarization balance through inhibiting the HIF-1α signaling pathway

  • Sci Rep. 2025 May 12;15(1):16424. doi: 10.1038/s41598-025-01286-7.
Bin Liu # 1,  Yuan Peng # 1,  Congling Wang 1,  Huixia Wei 2 3,  Shuqin Xu 1,  Yunfeng Liu 1,  Xuewei Yin 2 3,  Hongsheng Bi 2 3,  Dadong Guo # 4 5 6
Affiliations

Affiliations

  • 1 Shandong University of Traditional Chinese Medicine, No. 4655#, Daxue Road, Jinan, 250355, China.
  • 2 Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250002, China.
  • 3 Shandong Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases, Jinan, 250002, China.
  • 4 Shandong Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases, Jinan, 250002, China. dadonggene@sdutcm.edu.cn.
  • 5 Medical College of Optometry and Ophthalmology, Shandong University of Traditional Chinese Medicine, Jinan, 250002, China. dadonggene@sdutcm.edu.cn.
  • 6 Shandong Academy of Eye Disease Prevention and Therapy, No. 48#, Yingxiongshan Road, Jinan, 250002, China. dadonggene@sdutcm.edu.cn.
  • # Contributed equally.
PMID: 40355594 DOI: 10.1038/s41598-025-01286-7
Abstract

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.

Keywords

Baicalin; HIF-1α; Inflammation; M1/M2 macrophage; Uveitis.

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