Luoshi Neiyi Prescription inhibits estradiol synthesis and inflammation in endometriosis through the HIF1A/EZH2/SF-1 pathway.

Autor: Wu L; The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, China., Lan D; Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China., Sun B; Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China., Su R; Department of Gynecology, Guangzhou Hospital of Integrated Traditional Chinese and Western Medicine, Guangzhou, Guangdong, 510801, China., Pei F; Department of Gynecology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, China. Electronic address: peifangli5369@gzucm.edu.cn., Kuang Z; Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China., Su Y; Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China., Lin S; Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China., Wang X; Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China., Zhang S; Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China., Chen X; Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China., Jia J; Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China., Zeng C; Department of Gynecology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, China. Electronic address: drzcheng@gzucm.edu.cn.
Jazyk: angličtina
Zdroj: Journal of ethnopharmacology [J Ethnopharmacol] 2024 Dec 05; Vol. 335, pp. 118659. Date of Electronic Publication: 2024 Aug 02.
DOI: 10.1016/j.jep.2024.118659
Abstrakt: Ethnopharmacological Relevance: Endometriosis (EMS) is a common gynecological disease that causes dysmenorrhea, chronic pelvic pain and infertility. Luoshi Neiyi Prescription (LSNYP), a traditional Chinese medicine (TCM) formula, is used to relieve EMS in the clinic.
Aims: This study aimed to examine the active components of LSNYP and the possible mechanism involved in its treatment of EMS.
Materials and Methods: Ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) was used to identify the chemical components of LSNYP. Human primary ectopic endometrial stromal cells (ecESCs) and eutopic endometrial stromal cells (euESCs) were isolated, and the expression levels of hypoxia inducible factor 1A (HIF1A), enhancer of zeste homolog 2 (EZH2) and steroidogenic factor 1 (SF-1) were detected by immunofluorescence and qPCR. Cobalt chloride (CoCl 2 ) was utilized to construct an in vitro hypoxic environment, and lentiviruses were engineered to downregulate HIF1A and EZH2 and upregulate EZH2. Subsequently, the expression levels of HIF1A, EZH2, and SF-1 were measured using qPCR or western blotting. The binding of EZH2 to the SF-1 locus in ESCs was examined via ChIP. Furthermore, the effects of LSNYP on the HIF1A/EZH2/SF-1 pathway were evaluated both in vitro and in vivo.
Results: A total of 185 components were identified in LSNYP. The protein and gene expression levels of HIF1A and SF-1 were increased, whereas those of EZH2 were decreased in ecESCs. After treating euESCs with 50 μmol L -1 CoCl 2 for 24 h, cell viability and estradiol (E 2 ) production were enhanced. Hypoxia decreased EZH2 protein expression, while si-HIF1A increased it. SF-1 was increased when EZH2 was downregulated in normal and hypoxic environments, whereas the overexpression of EZH2 led to a decrease in SF-1 expression. ChIP revealed that hypoxia reduced EZH2 binding to the SF-1 locus in euESCs. In vitro, LSNYP-containing serum decreased E 2 and prostaglandin E 2 (PGE 2 ) production, inhibited cell proliferation and invasion, and reduced the expression of HIF1A, SF-1, steroidogenic acute regulatory protein (StAR), and aromatase cytochrome P450 (P450arom). In vivo, LSNYP suppressed inflammation and adhesion and inhibited the HIF1A/EZH2/SF-1 pathway in endometriotic tissues.
Conclusions: LSNYP may exert pharmacological effects on EMS by inhibiting E 2 synthesis and inflammation through regulation of the HIF1A/EZH2/SF-1 pathway. These results suggest that LSNYP may be a promising candidate for the treatment of EMS.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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