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Network pharmacology and biochemical experiments reveal the antiapoptotic mechanism of huperzine A for treating diabetic retinopathy
  1. Ying Zhang1,2,3,
  2. Wunan Huang4,
  3. Qing Tian1,2,3,
  4. Guannan Bai5,
  5. Wei Wu1,2,
  6. Houfa Yin1,2,
  7. Lidan Hu5,
  8. Xiangjun Chen1,2,3
  1. 1 Eye Center of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
  2. 2 Zhejiang Provincial Key Lab of Ophthalmology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
  3. 3 Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
  4. 4 Lanzhou University First Affiliated Hospital, Lanzhou University, Lanzhou, Gansu, China
  5. 5 National Clinical Research Center for Child Health, Zhejiang University School of Medicine Children's Hospital, Hangzhou, Zhejiang, China
  1. Correspondence to Dr Xiangjun Chen, Zhejiang University School of Medicine, Hangzhou 310020, China; chenxiangjun{at}zju.edu.cn; Mrs Lidan Hu; hulidan{at}zju.edu.cn

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.

  • pharmacology
  • retina
  • treatment medical
  • experimental and animal models
  • apotosis

Data availability statement

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Footnotes

  • YZ, WH and QT contributed equally.

  • Correction notice This paper has been amended since it was first published. An additiional corresponding author has been added.

  • Contributors YZ: performed experiments, methodology, investigation, original draft; WH: performed experiments, methodology; QT: performed experiments, analysed the data; GB: original draft, writing—review and editing; WW: writing—review and editing; HY: analysed the data; LH: conceived and designed the experiments, writing—review and editing; XC: supervision, writing—review and editing, funding acquisition. Xiangjun Chen is guarantor.

  • Funding This research was supported by the National Natural Science Foundation of China (No. grants 32271311 and 82200784 to LH, 31872724, and 81900837 to XC, 82271065 to WW, 82204713 to HF).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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