{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T04:22:20Z","timestamp":1787458940671,"version":"build-2736575974"},"reference-count":40,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009110","name":"Natural Science Foundation of Xinjiang Uygur Autonomous Region","doi-asserted-by":"crossref","award":["2022D01A57"],"award-info":[{"award-number":["2022D01A57"]}],"id":[{"id":"10.13039\/100009110","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100009110","name":"Natural Science Foundation of Xinjiang Uygur Autonomous Region","doi-asserted-by":"crossref","award":["2022D01B102"],"award-info":[{"award-number":["2022D01B102"]}],"id":[{"id":"10.13039\/100009110","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Industry-University Joint Talent Cultivation and Scientific Research Project, Xinjiang Institute for Advanced Study, Ministry of Education","award":["2026"],"award-info":[{"award-number":["2026"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: High-altitude hypobaric hypoxia (HH) is a major environmental stressor that impairs cognitive function, yet effective and widely available therapeutics remain limited. Although Rhodiola rosea has shown neuroprotective effects, its resource scarcity restricts large-scale application. Cistanche tubulosa (Schrenk) Wight, a traditional Chinese functional food, has been increasingly used in health supplements due to its anti-fatigue, anti-dementia, and memory-enhancing properties, suggesting potential benefits against hypoxia-induced cognitive impairment. Objective: This study aimed to investigate the effects of C. tubulosa ethanol extract (CTE) on hippocampal tissue and gut microbiota upon chronic HH exposure using SPF male Sprague\u2013Dawley (SD) rats. Methods: A total of 60 male SD rats were randomly assigned to six experimental groups (n = 10 per group): normoxic control, untreated HH model, positive control (R. rosea), and low-, medium-, high-dose CTE treatment groups. Behavioral tests (Morris water maze), hippocampal histopathology, serum and hippocampal oxidative stress markers (SOD, GSH-Px, MDA), expression of PI3K\/Akt\/mTOR-HIF-1\u03b1 signaling pathway proteins (by immunohistochemistry), and gut microbiota composition (by 16S rRNA sequencing) were evaluated. Results: The results demonstrated that CTE significantly improved cognitive function, enhanced SOD and GSH activities, and reduced MDA levels in both hippocampus and serum. CTE also modulated the expression of PI3K\/Akt\/mTOR-HIF-1\u03b1 pathway proteins in the hippocampus. Furthermore, CTE altered gut microbial diversity and abundance, increasing the proportion of beneficial bacteria, which may further influence hippocampal function via the gut\u2013brain axis. Conclusion: These findings provide scientific evidence for the application of C. tubulosa as a potential health supplement for high-altitude adaptation and lay a foundation for subsequent research.<\/jats:p>","DOI":"10.3390\/nu18162744","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T15:51:05Z","timestamp":1787327465000},"page":"2744","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cistanche tubulosa (Schrenk) Wight Extract Ameliorates Learning and Spatial Memory Abilities in High-Altitude Hypobaric Hypoxia Rats"],"prefix":"10.3390","volume":"18","author":[{"given":"Huanhuan","family":"Wang","sequence":"first","affiliation":[{"name":"College of Food Science and Pharmacy, Xinjiang Agricultural University, Urumqi 830052, China"},{"name":"College of Chemistry and Chemical Engineering, Xinjiang Agricultural University, Urumqi 830052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiqi","family":"Zeng","sequence":"additional","affiliation":[{"name":"College of Food Science and Pharmacy, Xinjiang Agricultural University, Urumqi 830052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwen","family":"Jing","sequence":"additional","affiliation":[{"name":"College of Chemistry and Chemical Engineering, Xinjiang Agricultural University, Urumqi 830052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojuan","family":"Mou","sequence":"additional","affiliation":[{"name":"College of Food Science and Pharmacy, Xinjiang Agricultural University, Urumqi 830052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenyan","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Food Science and Pharmacy, Xinjiang Agricultural University, Urumqi 830052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongliang","family":"Zhu","sequence":"additional","affiliation":[{"name":"College of Food Science and Pharmacy, Xinjiang Agricultural University, Urumqi 830052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Bao","sequence":"additional","affiliation":[{"name":"College of Food Science and Pharmacy, Xinjiang Agricultural University, Urumqi 830052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxin","family":"Zheng","sequence":"additional","affiliation":[{"name":"Xinjiang Key Laboratory for High Value Utilization of Agricultural and Livestock By-Products, Xinjiang Agricultural University, Urumqi 830052, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1016\/j.neuroscience.2018.07.026","article-title":"Hypobaric Hypoxia-Induced Learning and Memory Impairment: Elucidating the Role of Small Conductance Ca2+-Activated K+ Channels","volume":"388","author":"Kushwah","year":"2018","journal-title":"Neuroscience"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s12264-023-01099-6","article-title":"Impairment of Autophagic Flux After Hypobaric Hypoxia Potentiates Oxidative Stress and Cognitive Function Disturbances in Mice","volume":"40","author":"Dai","year":"2024","journal-title":"Neurosci. 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