Article ; Online: Juan-tong-yin potentially impacts endometriosis pathophysiology by enhancing autophagy of endometrial stromal cells via unfolded protein reaction-triggered endoplasmic reticulum stress.
2024 Volume 325, Page(s) 117859
Abstract: ... Although traditional Chinese medicines-such as Juan-Tong-Yin (JTY)-have shown promising results, their mechanisms of action remain ...
| Abstract | Ethnopharmacological relevance: Endometriosis (EMs) is characterized by inflammatory lesions, dysmenorrhea, infertility, and chronic pelvic pain. Single-target medications often fail to provide systemic therapeutic results owing to the complex mechanism underlying endometriosis. Although traditional Chinese medicines-such as Juan-Tong-Yin (JTY)-have shown promising results, their mechanisms of action remain largely unknown. Aim of the study: To elucidate the therapeutic mechanism of JTY in EMs, focusing on endoplasmic reticulum (ER) stress-induced autophagy. Materials and methods: The major components of JTY were detected using high-performance liquid chromatography-mass spectrometry (HPLC-MS). The potential mechanism of JTY in EMs treatment was predicted using network pharmacological analysis. Finally, the pathogenesis of EMs was validated in a clinical case-control study and the molecular mechanism of JTY was validated in vitro using endometrial stromal cells (ESCs). Results: In total, 241 compounds were analyzed and identified from JTY using UPLC-MS. Network pharmacology revealed 288 targets between the JTY components and EMs. Results of the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses indicated that regulating autophagy, migration, apoptosis, and inflammation were the key mechanisms of JTY in treating EMs. Meanwhile, we found that protein kinase R-like endoplasmic reticulum kinase (PERK), Beclin-1, and microtubule-associated protein light chain 3 B (LC3B) expressions were lower in endometria of patients with EMs than in those with normal eutopic endometria (p < 0.05). Additionally, during in vitro experiments, treatment with 20% JTY-containing serum significantly suppressed ESC proliferation, achieving optimal effects after 48 h. Electron microscopy revealed significantly increased autophagy flux in the JTY group compared with the control group. Moreover, JTY treatment significantly reduced the migratory and invasive abilities of ESCs and upregulated protein expression of PERK, eukaryotic initiation factor 2α (eIF2α)/phospho-eukaryotic initiation factor 2α (p-eIF2α), activating Transcription Factor-4 (ATF4), Beclin-1, and LC3BII/I, while subsequently downregulating NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and interleukin 18 (IL-18) expression. However, administration of GSK2656157-a highly selective PERK inhibitor-reversed these changes. Conclusion: JTY ameliorates EMs by activating PERK associated with unfolded protein reaction, enhancing cell ER stress and autophagy, improving the inflammatory microenvironment, and decreasing the migration and invasion of ESCs. |
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| MeSH term(s) | Female ; Humans ; Signal Transduction ; Beclin-1/metabolism ; Endometriosis/pathology ; Case-Control Studies ; Chromatography, Liquid ; Tandem Mass Spectrometry ; Endoplasmic Reticulum Stress ; Autophagy ; Apoptosis ; Stromal Cells/metabolism ; Stromal Cells/pathology ; Peptide Initiation Factors/metabolism ; Peptide Initiation Factors/pharmacology |
| Chemical Substances | Beclin-1 ; Peptide Initiation Factors |
| Language | English |
| Publishing date | 2024-02-03 |
| Publishing country | Ireland |
| Document type | Journal Article |
| ZDB-ID | 134511-4 |
| ISSN | 1872-7573 ; 0378-8741 |
| ISSN (online) | 1872-7573 |
| ISSN | 0378-8741 |
| DOI | 10.1016/j.jep.2024.117859 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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