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Introduction: Endometriosis (EMS) is characterized as a prevalent gynecological inflammatory disorder marked by the existence of endometrial tissues situated beyond the uterus. This condition leads to persistent pelvic pain and may contribute to infertility. In this investigation, we explored the potential mechanism underlying the development of endometriosis (EMS) triggered by transient exposure to either latent membrane protein 1 (LMP1) or Epstein-Barr virus (EBV) in a mouse model. Additionally, we examined the potential inhibitory effect of evodiamine (EDM) on EMS.Methods: Immortalized human endometrial stromal cells (HESC) or epithelial cells (HEEC) were transiently exposed to either EBV or LMP1. The presence of evodiamine (EDM) was assessed for its impact on estrogen receptor β (ERβ) expression, as well as on cell metabolism parameters such as redox balance, mitochondrial function, inflammation, and proliferation. Additionally, a mixture of LMP1-treated HESC and HEEC was administered intraperitoneally to generate an EMS mouse model. Different dosages of EDM were employed for treatment to evaluate its potential suppressive effect on EMS development.Results: Transient exposure to either EBV or LMP1 triggers persistent ERβ expression through epigenetic modifications, subsequently modulating related cell metabolism for EMS development. Furthermore, 4.0 µM of EDM can efficiently reverse this effect in in vitro cell culture studies. Additionally, 20 mg/kg body weight of EDM treatment can partly suppress EMS development in the in vivo EMS mouse model.Conclusion: Transient EBV/LMP1 exposure triggers permanent ERβ expression, favoring later EMS development, EDM inhibits EMS development through ERβ suppression. This presents a novel mechanism for the development of endometriosis (EMS) in adulthood stemming from early Epstein-Barr virus (EBV) exposure during childhood. Moreover, evodiamine (EDM) stands out as a prospective candidate for treating EMS.

Importance: The incidence of dyslipidemia increases after menopause. Menopause hormone therapy (MHT) is recommended for menopause related disease. However, it is benefit for lipid profiles is inconclusive.Objective: To conduct a systematic review and meta-analysis of randomized controlled trials to evaluate the effects of MHT on lipid profile in postmenopausal women.Evidence Review: Related articles were searched on PubMed/Medline, EMBASE, Web of Science, and Cochrane Library databases from inception to December 2020. Data extraction and quality evaluation were performed independently by two reviewers. The methodological quality was assessed using the “Cochrane Risk of Bias checklist”.Results: Seventy-three eligible studies were selected. The results showed that MHT significantly decreased the levels of TC (WMD: −0.43, 95% CI: −0.53 to −0.33), LDL-C (WMD: −0.47, 95% CI: −0.55 to −0.40) and LP (a) (WMD: −49.46, 95% CI: −64.27 to −34.64) compared with placebo or no treatment. Oral MHT led to a significantly higher TG compared with transdermal MHT (WMD: 0.12, 95% CI: 0.04–0.21). The benefits of low dose MHT on TG was also concluded when comparing with conventional-dose estrogen (WMD: −0.18, 95% CI: −0.32 to −0.03). The results also showed that conventional MHT significantly decreased LDL-C (WMD: −0.35, 95% CI: −0.50 to −0.19), but increase TG (WMD: 0.42, 95%CI: 0.18–0.65) compared with tibolone. When comparing with the different MHT regimens, estrogen (E) + progesterone (P) regimen significantly increased TC (WMD: 0.15, 95% CI: 0.09 to 0.20), LDL-C (WMD: 0.12, 95% CI: 0.07–0.17) and Lp(a) (WMD: 44.58, 95% CI:28.09–61.06) compared with estrogen alone.Conclusion and Relevance: MHT plays a positive role in lipid profile in postmenopausal women, meanwhile for women with hypertriglyceridemia, low doses or transdermal MHT or tibolone would be a safer choice. Moreover, E + P regimen might blunt the benefit of estrogen on the lipid profile.Clinical Trial Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42018092924], identifier [No. CRD42018092924].

Endometriosis is a common gynecological disease and causes severe chronic pelvic pain and infertility. Growing evidence showed that traditional Chinese medicine (TCM) plays an active role in the treatment of endometriosis. ELeng Capsule (ELC) is a Chinese medicine formula used for the treatment of endometriosis for several years. However, the mechanisms of ELC have not been fully characterized. In this study, network pharmacology and mRNA transcriptome analysis were used to study various therapeutic targets in ELC. As a result, 40 compounds are identified, and 75 targets overlapped with endometriosis-related proteins. The mechanism of ELC for the treatment of endometriosis is based on the function modules of inducing apoptosis, inhibiting angiogenesis, and regulating immunity mainly through signaling molecules and interaction (neuroactive ligand–receptor interaction), immune system–associated pathways (toll-like receptor signaling pathway), vascular endothelial growth factor (VEGF) signaling, and MAPK signaling pathway based on network pharmacology. In addition, based on RNA-sequence analysis, we found that the mechanism of ELC was predominantly associated with the regulation of the function modules of actin and cytoskeleton, epithelial–mesenchymal transition (EMT), focal adhesion, and immunity-associated pathways. In conclusion, ELC exerted beneficial effects on endometriosis, and the potential mechanism could be realized through functional modules, such as inducing apoptosis and regulating angiogenesis, cytoskeleton, and EMT. This work not only provides insights into the therapeutic mechanism of TCM for treating endometriosis but also offers an efficient way for drug discovery and development from herbal medicine.

Endometriosis is a common benign disease in women of reproductive age. It has been defined as a disorder characterized by inflammation, compromised immunity, hormone dependence, and neuroangiogenesis. Unfortunately, the mechanisms of endometriosis have not yet been fully elucidated, and available treatment methods are currently limited. The discovery of new therapeutic drugs and improvements in existing treatment schemes remain the focus of research initiatives. Chinese medicine can improve the symptoms associated with endometriosis. Many Chinese herbal medicines could exert antiendometriosis effects via comprehensive interactions with multiple targets. However, these interactions have not been defined. This study used association rule mining and systems pharmacology to discover a method by which potential antiendometriosis herbs can be investigated. We analyzed various combinations and mechanisms of action of medicinal herbs to establish molecular networks showing interactions with multiple targets. The results showed that endometriosis treatment in Chinese medicine is mainly based on methods of supplementation with blood-activating herbs and strengthening qi. Furthermore, we used network pharmacology to analyze the main herbs that facilitate the decoding of multiscale mechanisms of the herbal compounds. We found that Chinese medicine could affect the development of endometriosis by regulating inflammation, immunity, angiogenesis, and other clusters of processes identified by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The antiendometriosis effect of Chinese medicine occurs mainly through nervous system–associated pathways, such as the serotonergic synapse, the neurotrophin signaling pathway, and dopaminergic synapse, among others, to reduce pain. Chinese medicine could also regulate VEGF signaling, toll-like reporter signaling, NF-κB signaling, MAPK signaling, PI3K-Akt signaling, and the HIF-1 signaling pathway, among others. Synergies often exist in herb pairs and herbal prescriptions. In conclusion, we identified some important targets, target pairs, and regulatory networks, using bioinformatics and data mining. The combination of data mining and network pharmacology may offer an efficient method for drug discovery and development from herbal medicines.