Potential mechanism of Taohong Siwu Decoction in uterine fibroid treatment based on integrated strategy of network pharmacology and experimental verification

Abstract

Background: Taohong Siwu Decoction (THSWD) is a widely prescribed Traditional Chinese Medicine (TCM) for treating gynecological diseases. It is used to treat uterine fibroids (UF) in China, while its potential therapeutic effects and mechanism are unknown. Methods: The present study used network pharmacology to identify PI3K/AKT as one of the main THSWD signaling pathways that can be targeted to treat UF. The potential binding sites of miR-21-5p to PTEN were predicted using online databases. We were able to establish a UF rat model successfully. We selected the 15% THSWD serum after preparing THSWD drug-containing serum to culture tumor tissue-derived cells. These studies enabled us to assess the role of THSWD in UF improvement. Results: In vivo, we observed that low, medium, and high doses of THSWD improved histological changes in UF rats by increasing the expression levels of PTEN and miR-21-5p in their uterus while decreasing the expression levels of p-PI3K, p-AKT, and miR-21-5p. Treatment with THSWD medicated serum (15%) effectively inhibited the proliferation of cells derived from human UF and promoted apoptosis in vitro. PI3K phosphorylation, Akt phosphorylation, and miR-21-5p expression were decreased, while PTEN and cleaved caspase-3 were increased. These findings were reversed by administering 740 Y-P (a PI3K/Akt pathway agonist) and a miR-21-5p mimic. In addition, the double luciferase reporter gene assay confirmed the targeted binding relationship between miR-21-5p and PTEN. Conclusions: THSWD inhibited the expression and activation of the PI3K/AKT and miR-21-5p/PTEN pathways, resulting in anti-UF activity in leiomyoma cell models. Our findings suggest that THSWD could be used to treat UF.