The Mechanism of Compound Danshen Dripping Pills in the Treatment of Diabetic Retinopathy Based on Network Pharmacology and Molecular Docking

Abstract

BackgroundOur previous randomized, double-blind, placebo-controlled, multi-center clinical study showed that Compound Danshen Dripping Pills (CDDP) had a significant and safe effect in the treatment of diabetic retinopathy (DR), but its mechanism is still unclear, which we would explain based on network pharmacology and molecular docking.MethodThe active ingredients of CDDP (composed of Panax notoginseng, Salvia miltiorrhiza Bge., and Borneol) were searched in the TCMSP database. The validated target and Smiles number of the active ingredient are queried through the PubChem database, and the predicted target of the active ingredient is obtained through the Swisstarget Prediction database. The Drugbank, TTD, and DisGeNET databases were retrieved to obtain the related targets of DR. The core targets were obtained by the cluster analysis function of Cytoscape, and then the Protein-Protein Interaction was performed. The GO and KEGG signal pathways were enriched and clustered in David database. The potential active components and targets were docking with Autodock Vina, and the results were visualized by PyMOL.Result51 active components and 922 validation and prediction targets of CDDP, 715 targets of DR and 154 co-targets were obtained. Cluster analysis showed that there were two clusters, a total of 64 targets. Go and KEGG signal pathway enrichment analysis showed that the top 20 mainly included TNF and HIF-1 signaling pathway. In GO analysis, BP mainly includes positive regulation of smooth muscle cell proliferation and response to hypoxia, CC mainly includes extracellular space and extracellular domain, MF mainly includes protein binding and protein binding recognition. In KEGG database, the key genes in the TNF signaling pathway were TNF, NFkB and VEGF, in HIF-1 signaling pathway were the IL-6, STAT3, HIF1A and VEGF. Molecular docking results showed that all components of CDDP had a certain docking ability with TNF, NFkB, VEGF, IL-6, STAT3 and HIF1A, which of Asiatic acid and Salvianolic acid j was the strongest.Conclusion Based on the network pharmacology and molecular docking, the core active components of CDDP, mainly including Asiatic acid and Salvianolic acid j, which may play a role in regulating cell proliferation and response to inflammation and hypoxia by regulating the binding and recognition of intracellular and extracellular proteins, that is, mainly through TNF signaling pathway and HIF-1 signaling pathway.

Mechanism of traditional Chinese medicine in elderly diabetes mellitus and a systematic review of its clinical application

“…The age range of the included population ranged from 50 to 94 years old and the intervention period was 12 weeks to 6 months (Supplementary Table S4; Supplementary Table S5). (Wang and Su, 2007;Bai et al, 2008;Yi et al, 2009;Hong, 2010;Huang et al, 2010;Shu et al, 2010;Sun et al, 2012a;Sun et al, 2012b;Peng and Guo, 2013;Shen et al, 2013;Zhang et al, 2014a;Huang, 2014;Zhu, 2014;Hu et al, 2016;Li and Wang, 2016;Pan and Shang, 2016;Wang et al, 2016;Xie et al, 2016;Yang and Liu, 2016;Ma, 2017a;Chen, 2018;Hu, 2018;Wang, 2018;Wang and Cao, 2018;Fang et al, 2019;Lin et al, 2019;Shi et al, 2019;Su, 2020a;Li and Zhou, 2020;Zhong et al, 2020;Guo, 2021;Shen et al, 2021;Yu et al, 2021;Wang, 2022b;Liu et al, 2023a;Wang et al, 2023) The studies involved a total of 13 Traditional Chinese patent medicines, including Bailing Capsules (10 RCTs), Compound Danshen Dripping Pills (7 RCTs), Shenyan Kangfu Tablets (4 RCTs), Yishen Huashi Granules (4 RCTs), Jinshuibao Capsules (4 RCTs), Huangkui Capsules (2 RCTs), Bailing Tablets (1 RCTs), Congrong Yishen Granul...…”