Uncovering the protective mechanism of Taohong Siwu decoction against diabetic retinopathy via HIF-1 signaling pathway based on network analysis and experimental validation

Lei Wang,Jialun Du,Shuyan Li,Kai Lin,Wanhong Miao,Lei Zhang,Leilei Wang

doi:10.1186/s12906-020-03086-0

Abstract

BackgroundDiabetic retinopathy (DR) is a common and serious microvascular complication of diabetes. Taohong Siwu decoction (THSWD), a famous traditional Chinese medicine (TCM) prescription, has been proved to have a good clinical effect on DR, whereas its molecular mechanism remains unclear. Our study aimed to uncover the core targets and signaling pathways of THSWD against DR.MethodsFirst, the active ingredients of THSWD were searched from Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database. Second, the targets of active ingredients were identified from ChemMapper and PharmMapper databases. Third, DR associated targets were searched from DisGeNET, DrugBank and Therapeutic Target Database (TTD). Subsequently, the common targets of active ingredients and DR were found and analyzed in STRING database. DAVID database and ClueGo plug-in software were used to carry out the gene ontology (GO) and KEGG enrichment analysis. The core signaling pathway network of “herb-ingredient-target” was constructed by the Cytoscape software. Finally, the key genes of THSWD against DR were validated by quantitative real-time PCR (qRT-PCR).ResultsA total of 2340 targets of 61 active ingredients in THSWD were obtained. Simultaneously, a total of 263 DR-associated targets were also obtained. Then, 67 common targets were found by overlapping them, and 23 core targets were identified from protein-protein interaction (PPI) network. Response to hypoxia was found as the top GO term of biological process, and HIF-1 signaling pathway was found as the top KEGG pathway. Among the key genes in HIF-1 pathway, the mRNA expression levels of VEGFA, SERPINE1 and NOS2 were significantly down-regulated by THSWD (P < 0.05), and NOS3 and HMOX1 were significantly up-regulated (P < 0.05).ConclusionTHSWD had a protective effect on DR via regulating HIF-1 signaling pathway and other important pathways. This study might provide a theoretical basis for the application of THSWD and the development of new drugs for the treatment of DR.

Highlights

Diabetic retinopathy (DR) is a common and serious microvascular complication of diabetes
Data preparation Searching for active ingredients of Taohong Siwu decoction (THSWD) Ingredients of each herb in THSWD were searched from Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database, a
Candidate targets of THSWD against DR Active ingredients of THSWD A total of 722 ingredients in THSWD were found from TCMSP database

Summary

Introduction

Diabetic retinopathy (DR) is a common and serious microvascular complication of diabetes. Our study aimed to uncover the core targets and signaling pathways of THSWD against DR. Diabetic retinopathy (DR) is a common and serious microvascular complication of diabetes, which is an important cause of permanent vision loss in middle-aged and elderly people. One-third of people with diabetes have DR. [1] Previous study reported that 2.6 million people were visually impaired (moderate to severe vision impairment or even blindness) resulting from DR in 2015 and it was estimated to rise to 3.2 million in 2020 [2]. DR reduces the quality of life, and increases the risk of other diabetes complications and even mortality, which brings severe social and family burdens [3]. It is urgent to discover promising therapeutic targets and develop new therapeutic strategies for DR patients

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