Mechanism of quercetin in the treatment of endometriosis based on network pharmacology and transcriptome sequencing

This study explores how quercetin may treat endometriosis (EMs) by combining network pharmacology and transcriptome sequencing approaches. Through network pharmacology, 132 shared targets between quercetin and EMs were identified, with KEGG pathway analysis suggesting that the MAPK signaling pathway could be a significant therapeutic target. Transcriptome sequencing revealed that PDGFRB was highly expressed in ectopic endometrial tissue, a finding confirmed by immunohistochemistry (IHC) showing elevated levels of PDGFRB, RAS, RAF1, and ERK1/2 in ectopic lesions. In an EMs mouse model, quercetin treatment led to a marked reduction in ectopic lesion volume, lowered adhesion scores, and decreased expression of PDGFRB, RAS, RAF1, and ERK1/2 in endometrial tissues. Additionally, the knockdown of PDGFRB in endometriosis cells inhibited their proliferation, invasion, and migration, processes critical to EMs pathology. Quercetin treatment further suppressed cell viability and downregulated the protein expression of RAS, phosphorylated RAF1, RAF1, phosphorylated ERK, and ERK1/2. These findings collectively suggest that quercetin exerts its therapeutic effect in endometriosis by regulating the MAPK signaling pathway via PDGFRB, thereby reducing EMs cell proliferation, invasion, and migration. This study provides insights into quercetin's multi-targeted mechanism of action in endometriosis treatment. Overall design: Ectopic endometrial tissue and endometrial tissue were obtained from patients undergoing ovarian endometriosis resection in Shanghai Hospital of Traditional Chinese Medicine Affiliated to Shanghai University of Traditional Chinese Medicine from 2019 to 2020. The inclusion criteria were: endometriosis confirmed by pathological diagnosis. This study was approved by the Research Ethics Committee of Shanghai Hospital of Traditional Chinese Medicine, and all patients signed written informed consent. Statement: (1) The experiments were approved by the Ethics Committee of the Shanghai Hospital of Traditional Chinese Medicine (Approval No: 2020SHL-KYYS-102) and registered under clinical trial number SHDC2020CR4056 at the China Clinical Research Trial Registration Center (Registration No: ChiCTR2000036994). (1) All experiments were conducted in strict accordance with relevant guidelines and regulations. Patients for the study were recruited from the Shanghai Hospital of Traditional Chinese Medicine.Transcriptome sequencing was performed using 6 human ectopic endometrial tissue as well as endometrial tissue. poly (A)+ mRNA in total rna was enriched by oligo (dt) magnetic beads, and the library was purified and constructed. next generation sequencing (NGS) technology was used, and the library was paired-end based on Illumina sequencing platform, PE sequencing.