Network pharmacology and biochemical experiments reveal the antiapoptotic mechanism of huperzine A for treating diabetic retinopathy.

IF 3.7 2区医学 Q1 OPHTHALMOLOGY British Journal of Ophthalmology Pub Date : 2024-06-20 DOI:10.1136/bjo-2023-323639

Ying Zhang, Wunan Huang, Qing Tian, Guannan Bai, Wei Wu, Houfa Yin, Lidan Hu, Xiangjun Chen

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Abstract

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.

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网络药理学和生化实验揭示了胡朴素 A 治疗糖尿病视网膜病变的抗凋亡机制。

背景/目的：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，但目前尚无药物获准用于延缓或逆转视网膜神经变性。从蛇床子中分离出的天然生物碱 Huperzine A 在治疗神经退行性疾病方面具有保护神经和抗细胞凋亡的作用。我们的研究旨在探讨石杉碱甲在预防糖尿病视网膜病变的视网膜神经变性方面的作用及其可能的机制：方法：用链脲佐菌素诱导糖尿病视网膜病变模型。方法：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的病理损伤程度。网络药理学分析未揭示可能的分子机制，生化实验进一步验证了这一机制：结果：我们的研究表明，在糖尿病大鼠模型中，胡朴素 A 对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，胡朴素 A 可通过关键靶点 HSP27 和细胞凋亡相关途径治疗糖尿病视网膜病变。结论：我们的研究结果表明，Huperzine A 可能是一种预防糖尿病视网膜病变的潜在治疗药物。这是首次将网络药理学分析与生化研究结合起来，探讨胡朴素 A 预防糖尿病视网膜病变的机制。

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来源期刊

British Journal of Ophthalmology 医学-眼科学

CiteScore

10.30

自引率

2.40%

发文量

213

审稿时长

3-6 weeks

期刊介绍： The British Journal of Ophthalmology (BJO) is an international peer-reviewed journal for ophthalmologists and visual science specialists. BJO publishes clinical investigations, clinical observations, and clinically relevant laboratory investigations related to ophthalmology. It also provides major reviews and also publishes manuscripts covering regional issues in a global context.