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Article

Flavonoid Extract of Senecio Scandens Buch.-Ham. Ameliorates CTX-Induced Immunosuppression and Intestinal Damage via Activating the MyD88-Mediated Nuclear Factor-κB Signaling Pathway

1
Innovation Centre of Chinese Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China
2
State Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China
3
Key Biology Laboratory of Chinese Veterinary Medicine, Ministry of Agriculture and Rural Affairs, Beijing 100193, China
*
Authors to whom correspondence should be addressed.
Nutrients 2025, 17(15), 2540; https://doi.org/10.3390/nu17152540 (registering DOI)
Submission received: 15 June 2025 / Revised: 16 July 2025 / Accepted: 31 July 2025 / Published: 1 August 2025
(This article belongs to the Section Nutrition and Metabolism)

Abstract

Background/Objectives: Senecio 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—SSF) remain unclear. This study characterized SSF’s 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-α, IFN-γ, 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-κB pathway, with isoquercitrin identified as a pivotal bioactive constituent. Conclusions: SSF effectively mitigates CTX-induced immunosuppression and intestinal damage. These findings highlight SSF’s potential as a dual-functional natural agent for immunomodulation and intestinal protection. Subsequent research should validate isoquercitrin’s molecular targets and assess SSF’s clinical efficacy.
Keywords: Senecio scandens flavonoids; cyclophosphamide; immunomodulation; NF-κB signaling pathway; intestinal damage; gut microbiota Senecio scandens flavonoids; cyclophosphamide; immunomodulation; NF-κB signaling pathway; intestinal damage; gut microbiota

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MDPI and ACS Style

Zhu, X.; Zhang, L.; Ni, X.; Guo, J.; Fang, Y.; Xu, J.; Chen, Z.; Hao, Z. Flavonoid Extract of Senecio Scandens Buch.-Ham. Ameliorates CTX-Induced Immunosuppression and Intestinal Damage via Activating the MyD88-Mediated Nuclear Factor-κB Signaling Pathway. Nutrients 2025, 17, 2540. https://doi.org/10.3390/nu17152540

AMA Style

Zhu X, Zhang L, Ni X, Guo J, Fang Y, Xu J, Chen Z, Hao Z. Flavonoid Extract of Senecio Scandens Buch.-Ham. Ameliorates CTX-Induced Immunosuppression and Intestinal Damage via Activating the MyD88-Mediated Nuclear Factor-κB Signaling Pathway. Nutrients. 2025; 17(15):2540. https://doi.org/10.3390/nu17152540

Chicago/Turabian Style

Zhu, Xiaolin, Lulu Zhang, Xuan Ni, Jian Guo, Yizhuo Fang, Jianghan Xu, Zhuo Chen, and Zhihui Hao. 2025. "Flavonoid Extract of Senecio Scandens Buch.-Ham. Ameliorates CTX-Induced Immunosuppression and Intestinal Damage via Activating the MyD88-Mediated Nuclear Factor-κB Signaling Pathway" Nutrients 17, no. 15: 2540. https://doi.org/10.3390/nu17152540

APA Style

Zhu, X., Zhang, L., Ni, X., Guo, J., Fang, Y., Xu, J., Chen, Z., & Hao, Z. (2025). Flavonoid Extract of Senecio Scandens Buch.-Ham. Ameliorates CTX-Induced Immunosuppression and Intestinal Damage via Activating the MyD88-Mediated Nuclear Factor-κB Signaling Pathway. Nutrients, 17(15), 2540. https://doi.org/10.3390/nu17152540

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