A Network Pharmacology Approach to Explore the Mechanism of HuangZhi YiShen Capsule for Treatment of Diabetic Kidney Disease

Xue-Feng Zhou; Wei-E Zhou; Wen-Jing Liu; Min-Jing Luo; Xia-Qing Wu; Ying Wang; Peng Liu; Yu-Min Wen; Jia-Lin Li; Ting-Ting Zhao; Hao-Jun Zhang; Hai-Ling Zhao; Ping Li

doi:10.2478/jtim-2021-0020

A Network Pharmacology Approach to Explore the Mechanism of HuangZhi YiShen Capsule for Treatment of Diabetic Kidney Disease

J Transl Int Med. 2021 Jun 18;9(2):98-113. doi: 10.2478/jtim-2021-0020. eCollection 2021 Jun.

Authors

Xue-Feng Zhou^{1

2}, Wei-E Zhou^{2

3}, Wen-Jing Liu¹, Min-Jing Luo^{1

2}, Xia-Qing Wu⁴, Ying Wang^{1

2}, Peng Liu², Yu-Min Wen², Jia-Lin Li^{1

2}, Ting-Ting Zhao², Hao-Jun Zhang², Hai-Ling Zhao², Ping Li²

Affiliations

¹ Beijing University of Chinese Medicine, Beijing100029, China.
² Beijing Key Laboratory for Immune-Mediated Inflammatory Diseases, Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing100029, China.
³ Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing100730, China.
⁴ Faculty of Life Science and Medicine, Northwest University, No. 229 Taibai North Road, Xi'an, Shaanxi710069, China.

Abstract

Background and objective: HuangZhi YiShen Capsule (HZYS) is a Chinese patent herbal drug that protects kidney function in diabetic kidney disease (DKD) patients. However, the pharmacologic mechanisms of HZYS remain unclear. This study would use network pharmacology to explore the pharmacologic mechanisms of HZYS.

Methods: Chemical constituents of HZYS were obtained through the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and literature search. Potential targets of HZYS were identified by using the TCMSP and the SwissTarget Prediction databases. DKD-related target genes were collected by using the Online Mendelian Inheritance in Man, Therapeutic Target Database, GeneCards, DisGeNET, and Drugbank databases. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out to further explore the mechanisms of HZYS in treating DKD. Molecular docking was conducted to verify the potential interactions between the prime compounds and the hub genes.

Results: 179 active compounds and 620 target genes were obtained, and 571 common targets were considered potential therapeutic targets. The top 10 main active compounds of HZYS were heparin, quercetin, kaempferol, luteolin, methyl14-methylpentadecanoate, methyl (Z)-11-hexadecenoate, 17-hydroxycorticosterone, 4-pregnene-17α, 20β, 21-triol-3, 11-dione, wogonin, and hydroxyecdysone. Hub signaling pathways by which HZYS treating DKD were PI3K-Akt, MAPK, AGE-RAGE in diabetic complications, TNF, and apoptosis. The top 10 target genes associated with these pathways were IL6, MAPK1, AKT1, RELA, BCL2, JUN, MAPK3, MAP2K1, CASP3, and TNF. Quercetin and Luteolin were verified to have good binding capability with the hub potential targets IL6, MAPK1, AKT1 through molecular docking.

Conclusion: HZYS appeared to treat DKD by regulating the inflammatory, oxidative stress, apoptotic, and fibrosis signaling pathways. This study provided a novel perspective for further research of HZYS.

Keywords: HuangZhi YiShen Capsule; diabetic kidney disease; molecular docking; network pharmacology.