Exploration of the Specific Pathology of HXMM Tablet Against Retinal Injury Based on Drug Attack Model to Network Robustness

Abstract

Retinal degenerative diseases are related to retinal injury because of the activation of the complement cascade, oxidative stress-induced cell death mechanisms, dysfunctional mitochondria, chronic neuroinflammation, and production of the vascular endothelial growth factor. Anti-VEGF therapy demonstrates remarkable clinical effects and benefits in retinal degenerative disease patients. Hence, new drug development is necessary to treat patients with severe visual loss. He xue ming mu (HXMM) tablet is a CFDA-approved traditional Chinese medicine (TCM) for retinal degenerative diseases, which can alleviate the symptoms of age-related macular degeneration (AMD) and diabetic retinopathy (DR) alone or in combination with anti-VEGF agents. To elucidate the mechanisms of HXMM, a quantitative evaluation algorithm for the prediction of the effect of multi-target drugs on the disturbance of the disease network has been used for exploring the specific pathology of HXMM and TCM precision positioning. Compared with anti-VEGF agents, the drug disturbance of HXMM on the functional subnetwork shows that HXMM reduces the network robustness on the oxidative stress subnetwork and inflammatory subnetwork to exhibit the anti-oxidation and anti-inflammation activity. HXMM provides better protection to ARPE-19 cells against retinal injury after H2O2 treatment. HXMM can elevate GSH and reduce LDH levels to exhibit antioxidant activity and suppress the expression of IL-6 and TNF-α for anti-inflammatory activity, which is different from the anti-VEGF agent with strong anti-VEGF activity. The experimental result confirmed the accuracy of the computational prediction. The combination of bioinformatics prediction based on the drug attack on network robustness and experimental validation provides a new strategy for precision application of TCM.