Analysis of network pharmacological mechanism of Zhenlian Mingmu Capsule in treatment of diabetic retinopathy

Objective To investigate the mechanism of Zhenlian Mingmu Capsule in the treatment of diabetic retinopathy.

Methods The key targets of Zhenlian Mingmu Capsule in the treatment of diabetic retinopathy were screened by network pharmacology, and the binding sites of active ingredients were predicted by molecular docking. Combined with the results of network pharmacology, a rat model of diabetic retinopathy was established. Sixty rats were randomly divided into normal group, model group, calcium hydroxybenzene sulfonate tablet group and Zhenlian Mingmu Capsule group, with 15 rats in each group. The normal group and the model group were given 2 mL normal saline and gavage once a day; the calcium hydroxybenzene sulfonate tablet group and Zhenlian Mingmu Capsule group were respectively given the corresponding concentration of therapeutic drugs (2 mL), once a day. After 4 weeks of administration, retinal thickness, interleukin (IL) -1β, IL-6, tumor necrosis factor-α (TNF-α) levels, and protein expression levels of vascular endothelial growth factor (VEGF) and nuclear transcription factor-κB (NF-κB) were measured.

Results A total of 2 367 active ingredients of Zhenlian Mingmu Capsule were identified by network pharmacology, with 248 targets, 3 943 targets related to diabetic retinopathy, and 153 intersection targets. According to the analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), it was mainly involved in biological reaction processes such as signal transduction, inflammation and apoptosis, and mainly involved in the regulation of IL-1β, EGF/EGFR/P13K/AKT, IL-6/STAT3, TP53 and CASP3 signal pathways. The results of molecular docking showed that the main active ingredients obtained by screening had strong binding with the target. Compared with the normal group, retinal thickness in the model group was significantly decreased, and IL-1β, IL-6, TNF-α, VEGF, NF-κB were significantly increased (P < 0.05). Compared with the model group, the retinal thickness of rats in the calcium hydroxybenzene sulfonate tablet group was significantly increased, and IL-1β, IL-6, TNF-α, VEGF, NF-κB were significantly decreased (P < 0.05). Compared with the calcium hydroxybenzene sulfonate tablet group, retinal thickness in the Zhenlian Mingmu Capsule group was significantly increased, and IL-1β, IL-6, TNF-α, VEGF, NF-κB were significantly decreased (P < 0.05).

Conclusion Zhenlian Mingmu Capsule may have a positive effect in the treatment of diabetic retinopathy, and its mechanism may be related to the regulation of IL-1β, EGF/EGFR/P13K/AKT, IL6/STAT3, TP53 and CASP3 signaling pathways.