2. Academic Validation
  3. Gallic acid ameliorates endometrial hyperplasia through the inhibition of the PI3K/AKT pathway and the down-regulation of cyclin D1 expression

Gallic acid ameliorates endometrial hyperplasia through the inhibition of the PI3K/AKT pathway and the down-regulation of cyclin D1 expression

  • J Pharmacol Sci. 2024 May;155(1):1-13. doi: 10.1016/j.jphs.2024.02.015.
Caijie Zheng 1,  Yi Wang 2,  Beilei Bi 3,  Wencheng Zhou 4,  Xinran Cao 5,  Chenyang Zhang 5,  Wentian Lu 6,  Yang Sun 7,  Jiao Qu 8,  Wen Lv 9
Affiliations

Affiliations

  • 1 The Second Clinical School of Zhejiang Chinese Medicine University, Hangzhou, 310053, China.
  • 2 Colon and Rectal Surgery, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210001, China.
  • 3 Department of Gynecology, Tongde Hospital of Zhejiang Province, 234 Gucui Road, Hangzhou, 310012, China.
  • 4 The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, 310006, China.
  • 5 State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing, 210023, China.
  • 6 The First Clinical Medical College, Nanjing University of Chinese Medicine, 155 Hanzhong Road, Nanjing, Jiangsu, 210029, China.
  • 7 State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing, 210023, China; Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine in Prevention and Treatment of Tumor, Nanjing, Jiangsu, 210029, China. Electronic address: [email protected].
  • 8 State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 163 Xianlin Avenue, Nanjing, 210023, China. Electronic address: [email protected].
  • 9 Department of Gynecology, Tongde Hospital of Zhejiang Province, 234 Gucui Road, Hangzhou, 310012, China. Electronic address: [email protected].
PMID: 38553133 DOI: 10.1016/j.jphs.2024.02.015
Abstract

Background: Gallic acid (GA) is an organic compound with phenolic properties that occurs naturally and can be found in Guizhi Fuling capsules, showcasing a wide range of biological functionalities.

Purpose: The objective of this study was to examine the influence of GA on endometrial hyperplasia (EH) and elucidate its underlying mechanism.

Methods: Initially, the induction of EH was achieved by administering estradiol to mice via continuous subcutaneous injection for a duration of 21 days. Concurrently, GA treatment was administered, and subsequently, the uterine tissue structure was assessed using hematoxylin and eosin (H&E) staining. Following this, the proliferation of human endometrial cells treated by GA was determined utilizing the CCK-8 method. Furthermore, network pharmacology and single-cell-RNA-seq data were employed to identify the target of GA action. In addition, we will employ immunofluorescence (IF), immunohistochemistry (IHC), flow cytometry, western blot and RT-qPCR methodologies to investigate the impact of GA on the expression level of cyclin D1, PI3K, p-PI3K, Akt, p-AKT.

Results: GA treatment ameliorated histopathological alterations in the uterus and suppress proliferation. Estradiol stimulation can activate the PI3K/Akt pathway, leading to up-regulation of cyclin D1 expression, whereas GA treatment results in down-regulation of its expression.

Conclusions: The expression of cyclin D1 is down-regulated by GA through the inhibition of the PI3K/Akt pathway, effectively mitigating estradiol-induced EH in mice.

Keywords

Cyclin D1; Endometrial hyperplasia; Estradiol; Gallic acid; Network pharmacology; PI3K/AKT.

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