{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:38:34Z","timestamp":1760060314593,"version":"build-2065373602"},"reference-count":62,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,16]],"date-time":"2025-08-16T00:00:00Z","timestamp":1755302400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Natural Science Foundation of China","award":["32202850","ABDC-b202405","2024BZRC013"],"award-info":[{"award-number":["32202850","ABDC-b202405","2024BZRC013"]}]},{"name":"Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention","award":["32202850","ABDC-b202405","2024BZRC013"],"award-info":[{"award-number":["32202850","ABDC-b202405","2024BZRC013"]}]},{"name":"Guangxi University Natural Science and Technology Innovation Development Multiplier Program Project","award":["32202850","ABDC-b202405","2024BZRC013"],"award-info":[{"award-number":["32202850","ABDC-b202405","2024BZRC013"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Veterinary Sciences"],"abstract":"<jats:p>This study investigated the immunomodulatory effects and underlying mechanisms of total flavonoid of Spatholobus suberectus Dunn (TFSD) and its primary constituent formononetin (FMN) in immunosuppressed mouse models. Spatholobus suberectus Dunn (S. suberectus Dunn) was first analyzed qualitatively and quantitatively by broadly targeted metabolomics using Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS\/MS). Integrated network pharmacology and molecular docking approaches were used to investigate the potential mechanisms underlying S. suberectus Dunn\u2019s immunomodulatory effects. Subsequently, mice were pretreated with TFSD and FMN for seven days before constructing an immunosuppression model through intraperitoneal injection of 200 mg\/kg.bw cyclophosphamide (CTX). In vivo experiments validated the findings and investigated the mechanisms underlying the effects of TFSD and FMN on immunosuppression. Metabolomic analysis identified 501 distinct flavonoids in S. suberectus Dunn, with FMN exhibiting the highest relative abundance among all detected compounds. The primary active components of S. suberectus Dunn against immunosuppression are flavonoids, including FMN and vestitol. The core targets of these components were identified as NF-\u03baB and IKK\u03b2, with the NF-\u03baB signaling pathway being suggested as the most probable mechanism of action. FMN exhibited strong binding affinity to the core targets, NF-\u03baB p65 and IKK\u03b2. In vivo experiments indicated that pretreatment with TFSD and FMN prevented CTX-induced pathological damage in the spleen and thymus and increased immune cell counts and immunoglobulin levels. Additionally, it significantly upregulated the secretion and expression of key cytokines and the mRNA expression of NF-\u03baB p65, IKK\u03b1, and IKK\u03b2 (p &lt; 0.05 or p &lt; 0.01). In conclusion, TFSD and FMN can protect mice from CTX-induced immunosuppression by regulating the NF-\u03baB signaling pathway, making them promising drug candidates for preventing and treating immunosuppression-related diseases.<\/jats:p>","DOI":"10.3390\/vetsci12080762","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T16:22:33Z","timestamp":1755534153000},"page":"762","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Flavonoids of S. suberectus\u00a0Dunn Regulate Cyclophosphamide-Induced Immunosuppression Through NF-\u03baB Pathways"],"prefix":"10.3390","volume":"12","author":[{"given":"Jinwu","family":"Zhang","sequence":"first","affiliation":[{"name":"Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiqi","family":"Huang","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianhao","family":"Deng","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiying","family":"Liang","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6204-1826","authenticated-orcid":false,"given":"Jiakang","family":"He","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tingjun","family":"Hu","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liji","family":"Xie","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Veterinary Biotechnology, Guangxi Veterinary Research Institute, Nanning 530001, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hailan","family":"Chen","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9517-9802","authenticated-orcid":false,"given":"Meiling","family":"Yu","sequence":"additional","affiliation":[{"name":"Guangxi Key Laboratory of Animal Breeding, Disease Control and Prevention, College of Animal Science and Technology, Guangxi University, Nanning 530004, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,16]]},"reference":[{"key":"ref_1","first-page":"460","article-title":"Investigation on the immunomodulatory activities of Sarcodon imbricatus extracts in a cyclophosphamide (CTX)-induced immunosuppressanted mouse model","volume":"25","author":"Meng","year":"2017","journal-title":"Saudi Pharm. 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