文献类型：期刊文献

英文题名：Trans-Sodium Crocetinate Ameliorates High-Altitude Acute Lung Injury via Modulating EGFR/PI3K/AKT/NF-κB Signaling Axis

作者：Liang, Keke[1,2];Ta, Yanlin[1,2];Xu, Liang[1,2];Ma, Shuhe[1,2];Wang, Renjie[1,2];Xiao, Chenrong[2];Gao, Yue[2];Li, Maoxing[1,2]

第一作者：Liang, Keke

通信作者：Li, MX[1];Gao, Y[2];Li, MX[2]

机构：[1]Gansu Univ Chinese Med, Coll Pharm, Lanzhou 730013, Peoples R China;[2]Beijing Inst Radiat Med, Dept Pharmaceut Sci, Beijing 100850, Peoples R China

第一机构：甘肃中医药大学药学院（西北中藏药协同创新中心办公室）

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Coll Pharm, Lanzhou 730013, Peoples R China;[2]corresponding author), Beijing Inst Radiat Med, Dept Pharmaceut Sci, Beijing 100850, Peoples R China.|[1073501e14fb35863569f]甘肃中医药大学药学院（西北中藏药协同创新中心办公室）;[10735]甘肃中医药大学;

年份：2025

卷号：17

期号：15

外文期刊名：NUTRIENTS

收录：;Scopus(收录号：2-s2.0-105013313528);WOS:【SCI-EXPANDED(收录号:WOS:001549510200001)】；

基金：This study was supported by the Outstanding Doctoral Student Project of Gansu Province (25JRRA258) and the Traditional Chinese Medicine Innovation Team and Talent Support Program Project from the National Administration of Traditional Chinese Medicine (ZYYCXTDD-202207).

语种：英文

外文关键词：high-altitude acute lung injury; trans-sodium crocetinate; EGFR/PI3K/AKT/NF-kappa B signaling pathway; network pharmacology; molecular dynamics simulation

摘要：Objectives: Saffron, a traditional Chinese medicine, is renowned for its pharmacological effects in promoting blood circulation, resolving blood stasis, regulating menstruation, detoxification, and alleviating mental disturbances. Trans-crocetin, its principal bioactive component, exhibits significant anti-hypoxic activity. The clinical development and therapeutic efficacy of trans-crocetin are limited by its instability, poor solubility, and low bioavailability. Conversion of trans-crocetin into trans-sodium crocetinate (TSC) enhances its solubility, stability, and bioavailability, thereby amplifying its anti-hypoxic potential. Methods: This study integrates network pharmacology with in vivo and in vitro validation to elucidate the molecular targets and mechanisms underlying TSC's therapeutic effects against high-altitude acute lung injury (HALI), aiming to identify novel treatment strategies. Results: TSC effectively reversed hypoxia-induced biochemical abnormalities, ameliorated lung histopathological damage, and suppressed systemic inflammation and oxidative stress in HALI rats. In vitro, TSC mitigated CoCl2-induced hypoxia injury in human pulmonary microvascular endothelial cells (HPMECs) by reducing inflammatory cytokines, oxidative stress, and ROS accumulation while restoring mitochondrial membrane potential. Network pharmacology and pathway analysis revealed that TSC primarily targets the EGFR/PI3K/AKT/NF-kappa B signaling axis. Molecular docking and dynamics simulations demonstrated stable binding interactions between TSC and key components of this pathway. ELISA and RT-qPCR confirmed that TSC significantly downregulated the expression of EGFR, PI3K, AKT, NF-kappa B, and their associated mRNAs. Conclusions: TSC alleviates high-altitude hypoxia-induced lung injury by inhibiting the EGFR/PI3K/AKT/NF-kappa B signaling pathway, thereby attenuating inflammatory responses, oxidative stress, and restoring mitochondrial function. These findings highlight TSC as a promising therapeutic agent for HALI.