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Iranian Journal of Basic Medical Sciences، جلد ۲۹، شماره ۱، صفحات ۹۰-۱۰۰
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عنوان انگلیسی Parthenolide attenuated the endometriosis-like lesions by activating autophagy and suppressing NLRP3 inflammasome activity
چکیده انگلیسی مقاله Objective(s): Parthenolide (PTL) has significant anti-inflammatory and immunomodulatory effects, but its regulatory mechanisms in endometriosis (EMs) remain unclear. This study aimed to systematically evaluate the effects of PTL on cellular models and a murine EMs model, with a focus on its regulatory roles in autophagy and the NLRP3 inflammasome pathway.Materials and Methods: Human monocytic leukemia THP-1 cells, murine immortalized bone marrow-derived macrophages, and 30 female C57BL/6 mice were used. Autophagy-related proteins (Beclin1, LC3, p62) and inflammasome components (NLRP3, ASC, caspase-1) were detected by Western blotting, and the activation of the AMPK/ULK1 signaling pathway was assessed after treating with PTL at a concentration of 10 mg/ml for 1 hr. A murine EMs model was established by peritoneal implantation, followed by intraperitoneal injections of PTL (10 mg/ml). Immunohistochemical staining was performed to detect the expression of NLRP3, caspase-1, IL-1β, and GSDMD in ectopic lesions.Results: In vitro, PTL (10 mg/ml) significantly inhibited the activation of NLRP3, caspase-1-p20, IL-1β, and GSDMD, while increasing the phosphorylation levels of Beclin1 and AMPK/ULK1, and decreasing the expression of p62 and LC3, indicating enhanced autophagic flux. In vivo, PTL treatment markedly reduced the number, surface area, and weight of ectopic lesions in mice, and significantly suppressed the expression of inflammatory proteins in the lesions.Conclusion: PTL exerts its therapeutic effect on EMs by simultaneously activating autophagy through the AMPK/ULK1 signaling pathway and inhibiting the NLRP3 inflammasome and its downstream effectors.
کلیدواژه‌های انگلیسی مقاله Autophagic, Endometriosis, Inflammasomes, Inflammatory response, NLRP3 protein, Parthenolide
نویسندگان مقاله | Luhongyuan Jin
Department of Gynecology and Obstetrics, The Fourth Affiliated Hospital of Soochow University, Suzhou 215000, China


| Tingting Fu
Department of Orthopedics, The Fourth Affiliated Hospital of Soochow University, Suzhou 215000, China


| Chi Chi
Nanjing University of Chinese Medicine, Nanjing 210003, China


| Jiayi Zhou
Department of Gynecology and Obstetrics, The Fourth Affiliated Hospital of Soochow University, Suzhou 215000, China


| Jun Lin
Department of Orthopedics, The Fourth Affiliated Hospital of Soochow University, Suzhou 215000, China


| Wenjie Hou
Department of Gynecology and Obstetrics, The Fourth Affiliated Hospital of Soochow University, Suzhou 215000, China
نشانی اینترنتی https://ijbms.mums.ac.ir/article_26995.html
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