{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:21:04Z","timestamp":1790857264530,"version":"4.1.0"},"reference-count":59,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"State Key Research and Development Plan, China","award":["2022YFD1801105"],"award-info":[{"award-number":["2022YFD1801105"]}]},{"name":"State Key Research and Development Plan, China","award":["CARS-37"],"award-info":[{"award-number":["CARS-37"]}]},{"name":"China Agriculture Research System of MOF and MARA","award":["2022YFD1801105"],"award-info":[{"award-number":["2022YFD1801105"]}]},{"name":"China Agriculture Research System of MOF and MARA","award":["CARS-37"],"award-info":[{"award-number":["CARS-37"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives:\u00a0Senecio scandens Buch.-Ham. is a flavonoid-rich traditional medicinal plant with established immunomodulatory properties. However, the mechanisms underlying the immunoregulatory and intestinal protective effects of its flavonoid extract (Senecio scandens flavonoids\u2014SSF) remain unclear. This study characterized SSF\u2019s bioactive components and evaluated its efficacy against cyclophosphamide (CTX)-induced immunosuppression and intestinal injury. Methods: The constituents of SSF were identified using UHPLC\/Q-Orbitrap\/HRMS. Mice with CTX-induced immunosuppression were treated with SSF (80, 160, 320 mg\/kg) for seven days. Immune parameters (organ indices, lymphocyte proliferation, cytokine, and immunoglobulin levels) and gut barrier integrity markers (ZO-1, Occludin, Claudin-1 protein expression; sIgA secretion; microbiota composition) were assessed. Network pharmacology combined with functional assays elucidated the underlying regulatory mechanisms. Results: Twenty flavonoids were identified in SSF, with six prototype compounds detectable in the blood. The SSF treatment significantly ameliorated CTX-induced weight loss and atrophy of the thymus and spleen. It enhanced splenic T- and B-lymphocyte proliferation by 43.6% and 29.7%, respectively; normalized the CD4+\/CD8+ ratio (1.57-fold increase); and elevated levels of IL-2, IL-6, IL-10, TNF-\u03b1, IFN-\u03b3, IgM, and IgG. Moreover, SSF reinforced the intestinal barrier by upregulating tight junction protein expression and sIgA levels while modulating the gut microbiota, enriching beneficial taxa (e.g., the Lachnospiraceae_NK4A136_group, Akkermansia) and suppressing pathogenic Alistipes. Mechanistically, SSF activated the TLR\/MyD88\/NF-\u03baB pathway, with isoquercitrin identified as a pivotal bioactive constituent. Conclusions: SSF effectively mitigates CTX-induced immunosuppression and intestinal damage. These findings highlight SSF\u2019s potential as a dual-functional natural agent for immunomodulation and intestinal protection. Subsequent research should validate isoquercitrin\u2019s molecular targets and assess SSF\u2019s clinical efficacy.<\/jats:p>","DOI":"10.3390\/nu17152540","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T11:54:51Z","timestamp":1754308491000},"page":"2540","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Flavonoid Extract of Senecio scandens Buch.-Ham. Ameliorates CTX-Induced Immunosuppression and Intestinal Damage via Activating the MyD88-Mediated Nuclear Factor-\u03baB Signaling Pathway"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1155-5648","authenticated-orcid":false,"given":"Xiaolin","family":"Zhu","sequence":"first","affiliation":[{"name":"Innovation Centre of Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"},{"name":"State Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"},{"name":"Key Biology Laboratory of Chinese Veterinary Medicine, Ministry of Agriculture and Rural Affairs, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lulu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Innovation Centre of Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"},{"name":"State Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"},{"name":"Key Biology Laboratory of Chinese Veterinary Medicine, Ministry of Agriculture and Rural Affairs, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Ni","sequence":"additional","affiliation":[{"name":"Innovation Centre of Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"},{"name":"State Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"},{"name":"Key Biology Laboratory of Chinese Veterinary Medicine, Ministry of Agriculture and Rural Affairs, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Guo","sequence":"additional","affiliation":[{"name":"Innovation Centre of Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"},{"name":"State Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"},{"name":"Key Biology Laboratory of Chinese Veterinary Medicine, Ministry of Agriculture and Rural Affairs, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yizhuo","family":"Fang","sequence":"additional","affiliation":[{"name":"Innovation Centre of Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"},{"name":"State Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"},{"name":"Key Biology Laboratory of Chinese Veterinary Medicine, Ministry of Agriculture and Rural Affairs, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianghan","family":"Xu","sequence":"additional","affiliation":[{"name":"Innovation Centre of Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"},{"name":"State Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"},{"name":"Key Biology Laboratory of Chinese Veterinary Medicine, Ministry of Agriculture and Rural Affairs, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo","family":"Chen","sequence":"additional","affiliation":[{"name":"Innovation Centre of Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"},{"name":"State Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"},{"name":"Key Biology Laboratory of Chinese Veterinary Medicine, Ministry of Agriculture and Rural Affairs, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9516-6270","authenticated-orcid":false,"given":"Zhihui","family":"Hao","sequence":"additional","affiliation":[{"name":"Innovation Centre of Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"},{"name":"State Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China"},{"name":"Key Biology Laboratory of Chinese Veterinary Medicine, Ministry of Agriculture and Rural Affairs, Beijing 100193, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1016\/S0140-6736(00)04904-7","article-title":"An Overview of the Immune System","volume":"357","author":"Parkin","year":"2001","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1097\/LVT.0000000000000341","article-title":"Management of Long-Term Complications from Immunosuppression","volume":"30","author":"Russo","year":"2024","journal-title":"Liver Transpl."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1001\/jama.2023.28019","article-title":"Prevalence of Immunosuppression among US Adults","volume":"331","author":"Martinson","year":"2024","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"217119","DOI":"10.1016\/j.canlet.2024.217119","article-title":"Cyclophosphamide 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