文献类型：期刊文献

英文题名：Sheng-Xian-Tang alleviates endoplasmic reticulum stress, autophagy, and apoptosis through the PI3K/AKT/mTOR pathway in pulmonary fibrosis

作者：Ma, Quan[1,2];Yang, Hong[3];Zhu, Zhongbo[1];Luo, Caifeng[4];Wu, Yanlin[2];Zhang, Xuhui[2,5];Liu, Xiping[1]

第一作者：马泉

通信作者：Liu, XP[1];Zhang, XH[2]

机构：[1]Gansu Univ Tradit Chinese Med, Sch Basic Med Sci, Lanzhou 730000, Gansu, Peoples R China;[2]Gansu Univ Tradit Chinese Med, Affiliated Hosp, Dept Lung Dis, Lanzhou 730000, Gansu, Peoples R China;[3]Gansu Univ Tradit Chinese Med, Affiliated Hosp, Rehabil Med, Lanzhou 730000, Gansu, Peoples R China;[4]Gansu Univ Tradit Chinese Med, Affiliated Hosp, Dept Acupuncture & Moxibust, Gaolan Branch, Lanzhou 730000, Gansu, Peoples R China;[5]Gansu Univ Tradit Chinese Med, Affiliated Hosp 3, The Peoples Hosp Bai Yin City 1, Principals Off Meeting, Baiyin 730900, Gansu, Peoples R China

第一机构：甘肃中医药大学基础医学院（敦煌医学研究所）

通信机构：[1]corresponding author), Gansu Univ Tradit Chinese Med, Sch Basic Med Sci, Lanzhou 730000, Gansu, Peoples R China;[2]corresponding author), Gansu Univ Tradit Chinese Med, Affiliated Hosp, Dept Lung Dis, Lanzhou 730000, Gansu, Peoples R China.|[10735b845793de6ae2b30]甘肃中医药大学第二附属医院;[10735]甘肃中医药大学;[107351d2d02a88e1f325f]甘肃中医药大学基础医学院（敦煌医学研究所）;

年份：2026

卷号：22

期号：6

起止页码：495

外文期刊名：CURRENT PHARMACEUTICAL ANALYSIS

收录：;Scopus(收录号：2-s2.0-105045052345);WOS:【SCI-EXPANDED(收录号:WOS:001853160300001)】；

基金：This work was supported by National Natural Science Foundation (No. 82260889) and the Lanzhou City Science and Technology Development Guidance Plan Project (No. 2024-9-77).

语种：英文

外文关键词：Sheng-Xian-Tang; Pulmonary fibrosis; UPLC-HRMS; Endoplasmic reticulum stress; Autophagy; Apoptosis; PI3K/AKT/mTOR pathway

摘要：Background: Pulmonary fibrosis (PF) is a progressive interstitial lung disease with high morbidity and mortality. Sheng-Xian-Tang (SXT) has shown therapeutic potential against PF. This study aimed to elucidate the underlying mechanisms of SXT in PF. Methods: A bleomycin-induced PF rat model was established, and SXT-containing serum was prepared. Chemical constituents were identified using ultra-high performance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-HRMS). A549 cells were exposed to bleomycin with or without SXT-containing serum or pirfenidone (positive control). Fibrosis markers, apoptosis, ultrastructural changes, as well as proteins related to endoplasmic reticulum (ER) stress, autophagy, and apoptosis, were evaluated using ELISA, flow cytometry, transmission electron microscopy, and Western blotting. The PI3K/AKT/mTOR pathway was assessed following treatment with inavolisib, a PI3K inhibitor. Results: UPLC-HRMS identified five SXT-derived compounds in rat serum, including neomangiferin, isomangiferin, timosaponin B II, timosaponin A III, and (R)-2-hydroxystearate. In bleomycin-treated A549 cells, both SXT-containing serum and pirfenidone significantly reduced TGF-131 and alpha-SMA levels. Moreover, they alleviated ER dilation and reduced autophagosome and apoptotic body formation. These effects were accompanied by the downregulation of XBP1, GRP78, CHOP, LC313, caspase-12, caspase-3, and Bax, and the upregulation of p62 and Bcl-2. Furthermore, bleomycin-induced activation of the PI3K/AKT/mTOR pathway was markedly suppressed by SXT and inavolisib. Conclusion: SXT alleviates PF by attenuating ER stress and its downstream autophagy and apoptosis, potentially via inhibition of the PI3K/AKT/mTOR pathway. This study provides insight into the bioactive constituents of SXT, supporting its potential application in PF therapy. However, the findings are primarily based on in vitro experiments, and further in vivo validation is required to confirm the mechanisms.