{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T22:05:51Z","timestamp":1789164351185,"version":"build-2803163510"},"reference-count":27,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T00:00:00Z","timestamp":1753228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Outstanding Doctoral Student Project of Gansu Province","award":["25JRRA258"],"award-info":[{"award-number":["25JRRA258"]}]},{"name":"Outstanding Doctoral Student Project of Gansu Province","award":["ZYYCXTDD-202207"],"award-info":[{"award-number":["ZYYCXTDD-202207"]}]},{"name":"Traditional Chinese Medicine Innovation Team","award":["25JRRA258"],"award-info":[{"award-number":["25JRRA258"]}]},{"name":"Traditional Chinese Medicine Innovation Team","award":["ZYYCXTDD-202207"],"award-info":[{"award-number":["ZYYCXTDD-202207"]}]},{"name":"National Administration of Traditional Chinese Medicine","award":["25JRRA258"],"award-info":[{"award-number":["25JRRA258"]}]},{"name":"National Administration of Traditional Chinese Medicine","award":["ZYYCXTDD-202207"],"award-info":[{"award-number":["ZYYCXTDD-202207"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>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\u2019s 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-\u03baB 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-\u03baB, and their associated mRNAs. Conclusions: TSC alleviates high-altitude hypoxia-induced lung injury by inhibiting the EGFR\/PI3K\/AKT\/NF-\u03baB signaling pathway, thereby attenuating inflammatory responses, oxidative stress, and restoring mitochondrial function. These findings highlight TSC as a promising therapeutic agent for HALI.<\/jats:p>","DOI":"10.3390\/nu17152406","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T14:22:44Z","timestamp":1753280564000},"page":"2406","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Trans-Sodium Crocetinate Ameliorates High-Altitude Acute Lung Injury via Modulating EGFR\/PI3K\/AKT\/NF-\u03baB Signaling Axis"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-5799-0231","authenticated-orcid":false,"given":"Keke","family":"Liang","sequence":"first","affiliation":[{"name":"College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou 730013, China"},{"name":"Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanlin","family":"Ta","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou 730013, China"},{"name":"Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou 730013, China"},{"name":"Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhe","family":"Ma","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou 730013, China"},{"name":"Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renjie","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou 730013, China"},{"name":"Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenrong","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maoxing","family":"Li","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Gansu University of Chinese Medicine, Lanzhou 730013, China"},{"name":"Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s40101-020-00242-w","article-title":"NOD-like receptors mediate inflammatory lung injury during plateau hypoxia exposure","volume":"39","author":"Wang","year":"2020","journal-title":"J. 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