桃红四物汤（THSWD）是广泛应用于治疗妇科疾病的传统中药。在中国，它被用于治疗子宫肌瘤（UF），但其潜在的治疗效果和机制尚不清楚。本研究使用网络药理学方法确定PI3K/AKT作为THSWD的主要信号通路之一，可作为治疗UF的靶点。使用在线数据库预测miR-21-5p与PTEN的潜在结合位点。成功建立了UF大鼠模型。我们选择制备THSWD药物含量血清后的15％血清，用于培养肿瘤组织来源细胞。这些研究使我们能够评估THSWD在改善UF中的作用。体内观察到，低、中、高剂量的THSWD通过增加子宫中PTEN和miR-21-5p的表达水平，降低p-PI3K、p-AKT和miR-21-5p的表达水平，改善了UF大鼠的组织学变化。用THSWD药物血清（15％）处理有效抑制了来源于人类UF的细胞的增殖，并在体外促进了凋亡。PI3K磷酸化、Akt磷酸化和miR-21-5p表达减少，而PTEN和剪切的caspase-3增加。这些发现通过给予740 Y-P（一种PI3K/Akt途径激动剂）和miR-21-5p模拟物来逆转。此外，双荧光素酶报告基因实验证实了miR-21-5p与PTEN之间的靶向结合关系。THSWD抑制了PI3K/AKT和miR-21-5p/PTEN途径的表达与活化，从而在平滑肌瘤细胞模型中表现出抗UF活性。我们的发现表明，THSWD可用于治疗UF。© 2023. 作者（们）。

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.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.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.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.© 2023. The Author(s).