The Efficacy Mechanism of Epigallocatechin Gallate against Pre-Eclampsia based on Network Pharmacology and Molecular Docking

Pre-eclampsia (PE), a pregnancy complication, affects 3-5% of all pregnancies worldwide and is the main cause of maternal and perinatal morbidity. However, there is no drug which can clearly slow this disease progression. Epigallocatechin gallate (EGCG), a natural compound extracted from green tea, has been found to enhance the treatment efficacy of oral nifedipine against pregnancy-induced severe PE. This study aims to clarify the potential targets and pharmacological mechanisms of EGCG in treatment of PE. We used Traditional Chinese Medicine Systems Pharmacology database and Gene Cards database to obtain 179 putative target proteins of EGCG, 550 PE-related hub genes and 39 intersecting targets between EGCG and PE. By using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses, we got the gene entries and enrichment pathways closely related to the intersecting targets. The top 10 enrichment pathways were pathway in cancer, proteoglycans in cancer, HIF-1 signaling pathway, AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, bladder cancer, hepatitis B, IL-17 signaling pathway, toxoplasmosis, PI3K-Akt signaling pathway. Furthermore, compound-target-pathway (CTP) and protein-protein interaction (PPI) network analysis were employed to explore the interaction of the top twelve targets for EGCG in treating PE. Molecular docking analysis showed combinations between these targets and EGCG, and the interaction between EGCG and the targets IL-6 and EGFR was confirmed by using molecular dynamic simulation. In conclusion, these findings hint the underlying mechanism of EGCG in the treatment of PE and point out directions in further studies on PE.