Systems-Pharmacology-Based Identification of Antitumor Necrosis Factor Effect in Mimeng Flower Decoction for the Treatment of Diabetic Retinopathy

The traditional Chinese medicine of Mimeng flower decoction (MFD) is effective in treating diabetic retinopathy (DR), but the mechanism is still unclear. This study aims at investigating the mechanism of MFD in treating DR. First, active compounds in MFD were filtered out by the systems pharmacology method and used as bait to fish potential targets. The common genes between the targets and DR-related genes were selected to construct the compound-target-disease network and identify the network hub gene as a key gene. Molecular docking was simulated to assess the binding affinity of active compounds towards the gene protein. Streptozotocin- (STZ-) induced diabetic rat model was administered to evaluate the efficacy of MFD in treating DR and its effects on retinal gene expression. Finally, 53 active compounds were screened out from the seven herbs in MFD, with a total of 136 targets. After intersecting with 210 DR-related genes, 21 common genes were applied to construct the network, and tumor necrosis factor (TNF) was identified as the hub gene. The active compounds of acacetin, kaempferol, luteolin, and quercetin showed a good binding affinity towards TNF (C-score ≥ 4). In diabetic rats, MFD treatment reversed the retinal impairment and decreased retinal TNF expression significantly. In conclusion, this study adopted the method of systems pharmacology to screen out active compounds and construct the compound-target-disease network and found that MFD could ameliorate DR by downregulating the network hub gene of TNF.