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

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.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.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.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.