This study aims to investigate the impact of Polyphyllin VII (PP7) on pulmonary hypertension (PH) and elucidate the underlying mechanism involving microRNA (miR)-205-5p/β-catenin.The PH rat model was induced through hypoxia exposure. The effects of intraperitoneal injection of PP7 on pulmonary artery tissue pathology, hemodynamics, miR-205-5p expression and β-catenin protein levels were assessed. In vitro, pulmonary arterial smooth muscle cells (PASMCs) were subjected to hypoxic conditions. Moreover, miR-205-5p and/or β-catenin were overexpressed through transfection. PASMCs were pre-cultured in 20 μM PP7, and subsequent measurements included proliferation, apoptosis and vascular remodeling protein expression.PP7 ameliorated PH symptoms in rats, upregulated miR-205-5p expression and inhibited β-catenin protein expression. Furthermore, miR-205-5p upregulation inhibited β-catenin expression in PASMCs. The overexpression of β-catenin aggravated hypoxia-induced proliferation, inhibited apoptosis and further augmented VEGF and α-SMA protein expression. Additionally, miR-205-5p overexpression alleviated the hypoxia-induced PASMC proliferation and apoptosis by inhibiting β-catenin protein expression. Under hypoxic conditions, PP7 significantly elevated miR-205-5p while downregulating β-catenin protein expression. Furthermore, inhibiting miR-205-5p counteracted the inhibitory effect of PP7 on β-catenin, consequently blocking the regulatory role of PP7 in PASMC proliferation and apoptosis.PP7 likely modulates β-catenin protein levels by promoting miR-205-5p expression, thereby alleviating PH, vascular remodeling and airway smooth muscle remodeling.Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.