Dissecting the mechanism of Yuzhi Zhixue granule on ovulatory dysfunctional uterine bleeding by network pharmacology and molecular docking

Jialin Li; Hua Luo; Xinkui Liu; Jingyuan Zhang; Wei Zhou; Siyu Guo; Xiuping Chen; Yingying Liu; Shanshan Jia; Haojia Wang; Bingbing Li; Guoliang Cheng; Jiarui Wu

doi:10.1186/s13020-020-00392-0

Dissecting the mechanism of Yuzhi Zhixue granule on ovulatory dysfunctional uterine bleeding by network pharmacology and molecular docking

Chin Med. 2020 Oct 23:15:113. doi: 10.1186/s13020-020-00392-0. eCollection 2020.

Authors

Jialin Li^#¹, Hua Luo^#², Xinkui Liu¹, Jingyuan Zhang¹, Wei Zhou¹, Siyu Guo¹, Xiuping Chen², Yingying Liu¹, Shanshan Jia¹, Haojia Wang¹, Bingbing Li³, Guoliang Cheng³, Jiarui Wu¹

Affiliations

¹ Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, No. 11 of North Three-ring East Road, Chao Yang District, Beijing, 100102 China.
² Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macao, China.
³ State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Linyi, 276000 China.

^# Contributed equally.

Abstract

Background: Yuzhi Zhixue Granule (YZG) is a traditional Chinese patent medicine for treating excessive menstrual flow caused by ovulatory dysfunctional uterine bleeding (ODUB) accompanied by heat syndrome. However, the underlying molecular mechanisms, potential targets, and active ingredients of this prescription are still unknown. Therefore, it is imperative to explore the molecular mechanism of YZG.

Methods: The active compounds in YZG were screened by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The putative targets of YZG were collected via TCMSP and Search Tool for Interacting Chemicals (STITCH) databases. The Therapeutic Target Database (TTD) and Pharmacogenomics Knowledgebase (PharmGKB) databases were used to identify the therapeutic targets of ODUB. A protein-protein interaction (PPI) network containing both the putative targets of YZG and known therapeutic targets of ODUB was built. Furthermore, bioinformatics resources from the database for annotation, visualization and integrated discovery (DAVID) were utilized for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Finally, molecular docking was performed to verify the binding effect between the YZG screened compounds and potential therapeutic target molecules.

Results: The study employed a network pharmacology method, mainly containing target prediction, network construction, functional enrichment analysis, and molecular docking to systematically research the mechanisms of YZG in treating ODUB. The putative targets of YZG that treat ODUB mainly involved PTGS1, PTGS2, ALOX5, CASP3, LTA4H, F7 and F10. The functional enrichment analysis suggested that the produced therapeutic effect of YZG against ODUB is mediated by synergistical regulation of several biological pathways, including apoptosis arachidonic acid (AA) metabolism, serotonergic synapse, complement and coagulation cascades and C-type lectin receptor signaling pathways. Molecular docking simulation revealed good binding affinity of the seven putative targets with the corresponding compounds.

Conclusion: This novel and scientific network pharmacology-based study holistically elucidated the basic pharmacological effects and the underlying mechanisms of YZG in the treatment of ODUB.

Keywords: Mechanisms; Molecular Docking; Network pharmacology; Ovulatory Dysfunctional Uterine Bleeding; Yuzhi zhixue granule.