Background/aims Diabetic retinopathy is the most common eye disease that causes blindness in the working population. Neurodegeneration is the early sign of diabetic retinopathy, but no drug has been approved for delaying or reversing retinal neurodegeneration. Huperzine A, a natural alkaloid isolated from Huperzia serrata, displays neuroprotective and antiapoptotic effects in treating neurodegenerative disorders. Our study aims to investigate the effect of huperzine A in preventing retinal neurodegeneration of diabetic retinopathy and its possible mechanism. Methods Diabetic retinopathy model was induced by streptozotocin. H&E staining, optical coherence tomography, immunofluorescence staining and angiogenic factors were used to determine the degree of retinal pathological injury. The possible molecular mechanism was unrevealed by network pharmacology analysis and further validated by biochemical experiments. Results In our study, we demonstrated that huperzine A has a protective effect on the diabetes retina in a diabetic rat model. Based on the network pharmacology analysis and biochemical studies, huperzine A may treat diabetic retinopathy via key target HSP27 and apoptosis-related pathways. Huperzine A may modulate the phosphorylation of HSP27 and activate the antiapoptotic signalling pathway. Conclusion Our findings revealed that huperzine A might be a potential therapeutic drug to prevent diabetic retinopathy. It is the first-time combining network pharmacology analysis with biochemical studies to explore the mechanism of huperzine A in preventing diabetic retinopathy. No data are available.

中文翻译：

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网络药理学和生化实验揭示石杉碱甲治疗糖尿病视网膜病变的抗凋亡机制


背景/目标 糖尿病视网膜病变是导致工作人群失明的最常见眼病。神经变性是糖尿病视网膜病变的早期征兆，但尚未批准用于延迟或逆转视网膜神经变性的药物。石杉碱甲 (Huperzine A) 是一种从锯齿石杉 (Huperzia serrata) 中分离出来的天然生物碱，在治疗神经退行性疾病中表现出神经保护和抗细胞凋亡作用。本研究旨在探讨石杉碱甲预防糖尿病视网膜病变视网膜神经变性的作用及其可能机制。方法采用链脲佐菌素诱导糖尿病视网膜病变模型。采用H&E染色、光学相干断层扫描、免疫荧光染色和血管生成因子测定视网膜病理损伤程度。网络药理学分析揭示了可能的分子机制，并通过生化实验进一步验证。结果在我们的研究中，我们证明石杉碱甲对糖尿病大鼠模型的糖尿病视网膜具有保护作用。基于网络药理学分析和生化研究，石杉碱甲可能通过关键靶标HSP27和细胞凋亡相关途径治疗糖尿病视网膜病变。石杉碱甲可能调节 HSP27 的磷酸化并激活抗凋亡信号通路。结论 我们的研究结果表明石杉碱甲可能是预防糖尿病视网膜病变的潜在治疗药物。首次将网络药理学分析与生化研究相结合，探讨石杉碱甲预防糖尿病视网膜病变的作用机制。无可用数据。