Oxymatrine inhibits TGF‑β1‑mediated mitochondrial apoptotic signaling in alveolar epithelial cells via activation of PI3K/AKT signaling

Feng,Tong; Duan,Ran; Zheng,Pengcheng; Qiu,Jing; Li,Qingyuan; Li,Wancheng

doi:10.3892/etm.2023.11897

Oxymatrine inhibits TGF‑β1‑mediated mitochondrial apoptotic signaling in alveolar epithelial cells via activation of PI3K/AKT signaling

Authors:
- Tong Feng
- Ran Duan
- Pengcheng Zheng
- Jing Qiu
- Qingyuan Li
- Wancheng Li
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Affiliations: Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan 610500, P.R. China, School of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan 610500, P.R. China
Published online on: March 20, 2023 https://doi.org/10.3892/etm.2023.11897
Article Number: 198
Copyright: © Feng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Although pulmonary fibrosis (PF) causes respiratory failure and death, effective therapies for PF have not been developed. Oxymatrine (OMT), an active ingredient in the Chinese herb Sophora flavescens, exerts antifibrotic effects; however, its effect on PF remains unclear. The present study aimed to determine whether OMT decreases transforming growth factor‑β1 (TGF‑β1)‑induced PF in human lung cancer A549 cells by inhibiting apoptosis and targeting the phosphoinositide 3‑kinase (PI3K)/protein kinase B (AKT) pathway. To construct a PF cell model, A549 cells were stimulated with TGF‑β1. The experimental groups were as follows: control (untreated cells grown in complete medium), TGF‑β1 (cells treated with 5 ng/ml TGF‑β1), OMT (cells treated with 5 ng/ml TGF‑β1 and 0.25, 0.50, or 1.00 mg/ml OMT), and OMT + LY294002 (cells treated with 5 ng/ml TGF‑β1, 1.0 mg/ml OMT. and 25 µmol/l LY294002). The effects of OMT on cell morphology (via electron microscopy), apoptosis (via Annexin V‑PI staining), mitochondrial apoptosis signaling [using JC‑1 method to analyze mitochondrial membrane potential (MMP)], and Bcl‑2, as well as Bax expression (via western blotting and reverse transcription‑quantitative polymerase chain reaction), were analyzed. OMT significantly protected cells against TGF‑β1‑induced PF by inhibiting apoptosis. The specific manifestations were cell injury, as evidenced by morphological changes and decreased MMP. Following OMT treatment, the expression of the pro‑apoptotic protein Bax increased, whereas that of the anti‑apoptotic protein Bcl‑2 decreased. The PI3K/AKT‑specific inhibitor LY294002 significantly inhibited the ameliorative effects of OMT on TGF‑β1‑induced apoptosis. Collectively, OMT attenuated TGF‑β1‑mediated mitochondrial apoptosis of alveolar epithelial cells by activating the PI3K/AKT signaling pathway. Therefore, OMT may be a promising drug for PF treatment.

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