A Network Pharmacology Based Analysis of The Potential Mechanisms of Compound Danshen Dripping Pill for Treatment of Diabetic Retinopathy

Abstract

Background: Diabetic retinopathy (DR) has become a worldwide concern in recent years because of the high prevalence and vision-threat. The limited therapies have been in stark contrast to its high prevalence. On top of that, almost all the treatments, like laser, are applied only at the end stage of this disease. However, with the development of network pharmacology, a traditional Chinese medicine (TCM), Compound Danshen Dripping Pill (CDDP), may bring some new insights into the early intervention of DR. Methods: The active compounds and potential targets of CDDP and DR-related targets were collected from the TCMSP, UniProt, GeneCards and OMIM databases. And protein-protein interactions (PPI) information was achieved from the STRING database. The gene enrichment analysis of GO and KEGG was carried out by “clusterProfiler” in R software. The collected data was then used to form network maps of compound-target and PPI, or visualized by the software of Cytoscape. Results: 54 compounds and 50 targets were identified for CDDP against DR. Among the predicted effective compounds, 29 tanshinones from Radix Salviae (Danshen) were identified. And the core targets might be estrogen receptor (ESR1), androgen receptor (AR), caspase-3 (CASP3), Interleukin-6 (IL6) and vascular endothelial growth factor A (VEGFA) in 50 targets. There were 266 significantly correlated biological processes such as steroid hormone response, oxidative stress and apoptosis enriched out. Besides, The 50 targets significantly participate in 97 pathways and mainly enriched in advanced glycation end products (AGE)-receptor for advanced glycation end products (RAGE), fluid shear stress and atherosclerosis, apoptosis and VEGF signal pathway et al.Conclusions: The mechanisms of CDDP for treating DR may involve multi-compound, multi-target and multi-pathway synergistic effects. It may participate in the regulation of steroid hormone response, oxidative stress, apoptosis and hemodynamics in diabetic retina. Tanshinones and luteolin from Radix Salviae were probably responsible for the effectiveness of CDDP on DR.

An evidence mapping study based on systematic reviews of TCM for diabetic retinopathy

“…Usual care+Calcium Dobesilate ROB Hu ZY,2022 [35] 1379 Huoxue Huayu Method+Control Calcium Dobesilate ROB Duan JN,2022 [36] 4852 TCM+Control Anti VEGF+Laser photocoagulation surgery ROB Hu ZP,2021 [37] qi ming granule+Control placebo/Usual care ROB Xu JY,2021 [38] 1145 acupuncture Western medicine+TCM ROB Liu WQ,2021 [39] 180 acupuncture+TCM Usual care ROB Pang B,2020 [40] 3430 Huoxue Huayu Method+Control Usual care/placebo ROB An XD,2020 [41] 1522 TCM+Control Western medicine ROB Yang XR,2020 [42] 1250 TCM+Control Western medicine ROB Wang MR,2020 [43] 2601 CDDP+Control Calcium Dobesilate/placebo ROB Su MG,2020 [44] 1664 qi ming granule Usual care Jadad Scale Cheng JJ,2020 [45] 1778 Compound thrombosis capsule+Control Calcium Dobesilate ROB Ou C,2019 [46] 661 Yiqi Yangyin Method+Control…”