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

Abstract

BackgroundGallic 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. PurposeThe objective of this study was to examine the influence of GA on endometrial hyperplasia (EH) and elucidate its underlying mechanism. MethodsInitially, 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. ResultsGA 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. ConclusionsThe expression of cyclin D1 is down-regulated by GA through the inhibition of the PI3K/AKT pathway, effectively mitigating estradiol-induced EH in mice.