Journal of Otolaryngology and Ophthalmology of Shandong University ›› 2023, Vol. 37 ›› Issue (1): 94-104.doi: 10.6040/j.issn.1673-3770.0.2021.481

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Analysis of the effect of berberine on diabetic retinopathy in the immune microenvironment based on network pharmacology and experimental verification

LIU Tong1, LIN Wei2, FENG Meng2, YANG Yi1, LIU Tingting3, ZHANG Min1   

  1. 1. Basic Medical School, Xizang Minzu University, Xianyang 712082, Shan xi China;
    2. School of Clinical and Basic Medicine(Institute of Basic Medicine), Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan 250032, Shandong, China;
    3. Internal Medicine of Fundus Diseases, Eye Hospital of Shandong First Medical University (Shandong Eye Hospital), Jinan 250021, Shandong, China
  • Published:2023-02-06

Abstract: Objective To study the immune mechanism of berberine(BBR)in the treatment of diabetic retinopathy(DR)using network pharmacology and animal model experiments. Methods Chemical constituents and potential BBR targets were obtained from a traditional Chinese medicine database(HERB), target genes related to DR pathogenesis were identified in the DisGeNET and GeneCards databases, and the protein interaction network was drawn using a combination of the String database and Cytoscape software. The BBR target(s)acting on DR were screened out by network topology analysis and the GO cell composition, biological processes, molecular function, and KEGG pathways of these targets were analyzed using the Metascape bioinformatics database. Following this, a BBR “target-path” network diagram was constructed and analyzed with Cytoscape, the molecular docking ability of drug ligands and targets was predicted with Pymol, and, finally, a diabetic mouse model was established, treated with BBR 100 mg/(kg·d)for 8 weeks, and then had retinal tissue sections taken and stained to detect the degree of pathological change. The proportion of CD4+ and IL-17+ T cells in the eyes and lymph nodes of diabetic mice was determined by flow cytometry. Results 67 common BBR and DR targets were screened from the traditional Chinese medicine database, including INS, IL-6, CASP3, TNF and VEGFA as the core BBR targets which affect DR. The GO analysis suggested that BBR could play a role in the treatment of DR through response to oxidative stress and regulation of apoptotic signaling pathway. KEGG pathway enrichment analysis identified the IL-17 signaling and Th17 differentiation pathways as potential target pathways for BBR suppression of immune inflammation. The core targets identified were RELA, MAPK1, IL-6, NFKBIA, and TNF. Molecular docking showed a strong binding force between BBR and RELA, MAPK1, and IL-6. The tissue sections from diabetic mice revealed alleviated retinal pathology following BBR treatment, and the number of CD4+ and IL-17+ T cells were significantly lower in the treatment group. Conclusion BBR can inhibit the DR inflammatory response by regulating the Th17/IL-17 signaling pathway. This is a newly identified immune mechanism of BBR, and provides a theoretical basis for further exploration of the pharmacological targets and mechanisms of BBR in the treatment of DR.

Key words: Diabetic retinopathy, Berberine, Immune microenvironment, Network pharmacology, Molecular docking

CLC Number: 

  • R774.1
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