2. Academic Validation
  3. Paeonol ameliorates endometrial hyperplasia in mice via inhibiting PI3K/AKT pathway-related ferroptosis

Paeonol ameliorates endometrial hyperplasia in mice via inhibiting PI3K/AKT pathway-related ferroptosis

  • Phytomedicine. 2023 Jan:109:154593. doi: 10.1016/j.phymed.2022.154593.
Songjun Liu 1,  Xinran Cao 2,  Tao Zhang 2,  Chenyang Zhang 2,  Jiao Qu 2,  Yang Sun 3,  Wen Lv 4,  Fan Qu 5
Affiliations

Affiliations

  • 1 Women's Hospital, School of Medicine, Zhejiang University, 1 Xueshi Road, Hangzhou 310006, Zhejiang, China; Department of Gynecology, Tongde Hospital of Zhejiang Province, 234 Gucui Road, Hangzhou 310012, Zhejiang, China.
  • 2 State Key Laboratory of Pharmaceutical Biotechnology, Department of Biotechnology and Pharmaceutical Sciences, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing 210023, China.
  • 3 State Key Laboratory of Pharmaceutical Biotechnology, Department of Biotechnology and Pharmaceutical Sciences, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing 210023, China. Electronic address: [email protected].
  • 4 Department of Gynecology, Tongde Hospital of Zhejiang Province, 234 Gucui Road, Hangzhou 310012, Zhejiang, China. Electronic address: [email protected].
  • 5 Women's Hospital, School of Medicine, Zhejiang University, 1 Xueshi Road, Hangzhou 310006, Zhejiang, China. Electronic address: [email protected].
PMID: 36610113 DOI: 10.1016/j.phymed.2022.154593
Abstract

Background: Paeonol (Pae) is one of the active ingredients from components of Guizhi Fuling Capsule, a traditional Chinese medicine widely used for the treatment of women's diseases, which exhibits various biological and pharmacological activities.

Purpose: The objective of this study was to investigate the molecular mechanism underlying the role of Pae in protecting against endometrial hyperplasia (EH).

Methods: CCK-8 assay was performed to detect the effect of Pae on cell proliferation. Hematoxylin and eosin (H&E) staining was performed to evaluate uterine tissue structure. A network pharmacology study was performed to search the disease targets. Single-cell transcriptome analysis was performed with uterine tissues from 3 healthy donors and 3 EH patients on 10X Genomics platform. Changes in lipid peroxidation were detected by the MDA reaction. IHC assay, Western blot, immunofluorescence and RT-qPCR were used to study the effects of estradiol and Pae on the expression levels of GPX4, PI3K, Akt, p-PI3K, p-AKT in mice.

Results: Pae treatment resulted in a decrease in cell viability of endometrial epithelial cells. Loss of uterus weight and morphology changes were observed in mice. In addition, Fe iron concentration and MDA levels increased, while the expression of GPX4, p-PI3K and p-AKT diminished.

Conclusions: Pae exhibited obvious alleviative activity in estradiol-induced mice via PI3K/Akt signaling pathway-regulated Ferroptosis.

Keywords

Endometrial hyperplasia; Ferroptosis; PI3K/AKT; Paeonol; TCM.

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