{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T02:08:16Z","timestamp":1778810896287,"version":"3.51.4"},"reference-count":35,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T00:00:00Z","timestamp":1761177600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Yunnan Major Scientific and Technological Projects","award":["202202AG050021"],"award-info":[{"award-number":["202202AG050021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Steamed Panax notoginseng saponins (SPNSs) can alleviate cyclophosphamide-induced anemia. However, the hepatointestinal effects of SPNSs and their role in ameliorating cyclophosphamide-induced anemia remain unexplored. Objective: To elucidate the hepatointestinal effects of SPNSs and their role in ameliorating cyclophosphamide-induced anemia. Methods: Blood samples were collected and analyzed on days 7 and 14. Liver tissues and small intestinal villi structures were observed via HE staining. Liver and colon content metabolites were detected by liquid chromatography-tandem mass spectrometry (LC-MS\/MS). Liver proteins were analyzed by using an Orbitrap Astral mass spectrometer. Colon content microbiota composition was assessed via metagenomics. Signaling pathway protein expression was analyzed via Western blotting (WB). Results: SPNSs significantly increased the red blood cell (RBC) count and hemoglobin (HGB) level by day 14 and alleviated hepatointestinal damage. Hepatic metabolomics revealed: the most abundant metabolites were fatty acids and stachyose on day 7 and amino acid and arachidonic acid derivatives on day 14. KEGG analysis implicated cAMP signaling. Proteomics revealed upregulated immune-related proteins and enhanced PI3K pathway activity (WB-validated). Colon content metabolomics showed increased daidzein, 3-(2,5-dimethoxyphenyl) propanoic acid, \u03b3-CEHC, and adenosine in SPNS groups on day 14. Metagenomics indicated differential abundances of Heminiphilus faecis, Phocaeicola sartorii, and s-bacterium_J10.2018 on day 14. Multiomics integration demonstrated significant correlations between hepatic metabolites, hematopoietic proteins, colon content metabolites, and probiotic bacteria. Conclusions: SPNS alleviates cyclophosphamide-induced hepato-intestinal injury in anemic mice by modulating the gut microbiota and enhancing hepato-intestinal immune defense. Additionally, SPNSs ameliorate anemia in cyclophosphamide-treated mice by activating the cAMP\/PI3K\/AKT pathway, promoting hepatocyte proliferation, and increasing hematopoietic protein expression.<\/jats:p>","DOI":"10.3390\/nu17213335","type":"journal-article","created":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T01:35:11Z","timestamp":1761269711000},"page":"3335","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Steamed Panax notoginseng Saponins Ameliorate Cyclophosphamide-Induced Anemia by Attenuating Gut-Liver Injury and Activating the cAMP\/PI3K\/AKT Signaling Pathway"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5549-0906","authenticated-orcid":false,"given":"Cuiping","family":"Xu","sequence":"first","affiliation":[{"name":"Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China"},{"name":"Southwest United Graduate School, Kunming 650500, China"},{"name":"Yunnan Key Laboratory of <i>Panax notoginseng<\/i>, Kunming 650500, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Cui","sequence":"additional","affiliation":[{"name":"Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China"},{"name":"Yunnan Key Laboratory of <i>Panax notoginseng<\/i>, Kunming 650500, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qionglian","family":"Fang","sequence":"additional","affiliation":[{"name":"Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China"},{"name":"Yunnan Key Laboratory of <i>Panax notoginseng<\/i>, Kunming 650500, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pengfei","family":"Tu","sequence":"additional","affiliation":[{"name":"Southwest United Graduate School, Kunming 650500, China"},{"name":"State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiuming","family":"Cui","sequence":"additional","affiliation":[{"name":"Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China"},{"name":"Southwest United Graduate School, Kunming 650500, China"},{"name":"Yunnan Key Laboratory of <i>Panax notoginseng<\/i>, Kunming 650500, China"},{"name":"Laboratory of Sustainable Utilization of <i>Panax notoginseng<\/i> Resources, State Administration of Traditional Chinese Medicine, Kunming 650500, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1142\/S0192415X14500098","article-title":"Effects of carnosine on cyclophosphamide-induced hematopoietic suppression in mice","volume":"42","author":"Xu","year":"2014","journal-title":"Am. 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