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

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.

Evaluation of the Efficacy and Adverse Reactions of Mirena Combined with Hysteroscopic Surgery When Treating AUB: Based on a Retrospective Cohort Study

“…There are some problems such as poor compliance during treatment and easy recurrence after treatment. Other studies have indicated that, long-term oral hormone drugs increased the incidence of cardiovascular and cerebrovascular diseases, endometrial cancer, and breast cancer to a certain extent [ 15 ]. The perimenopausal AUB-O patients with poor effect of repeated drugs and conservative treatment finally need to choose surgical hysterectomy, but conventional hysterectomy has some problems, such as trauma, long recovery period, operation, and postoperative complications [ 16 ].…”

Elucidating the anti-aging mechanism of Si Jun Zi Tang by integrating network pharmacology and experimental validation in vivo

“…To improve the accuracy of the connection between small molecular compounds and the core target proteins, we used molecular docking to evaluate the interactions between compounds and target proteins. It is generally believed that when the binding energy of a ligand and receptor is <−4 kcal/mol, there is potential binding activity between the ligand and receptor [ 35 ]. A binding energy score less than −5 kcal/mol suggests strong binding between the ligand and receptor [ 36 , 37 ].…”

Exploring the Therapeutic Mechanism of Tingli Dazao Xiefei Decoction on Heart Failure Based on Network Pharmacology and Experimental Study

“…Because beta-carotene has no free hydrogen bond, it cannot stably bind to the target through hydrogen bond, so it is eliminated. It is generally believed that when the binding energy of ligand and receptor is <−4 kcal/mol, there is potential binding activity between them; binding energy <−5 kcal/mol suggests a significant binding ability between them [ 32 ]. Our docking results showed that the binding energy of the receptor proteins and the active ingredients were all lower than −5 kcal/mol, indicating that the receptor proteins and the active ingredients were well bound, which further provides evidence support for TDXD treatment of HF ( Table 1 ).…”