{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:02:45Z","timestamp":1780444965505,"version":"3.54.1"},"reference-count":42,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Jilin Province Science and Technology Development Plan Item","award":["20250203067SF"],"award-info":[{"award-number":["20250203067SF"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Chemotherapy-induced gonadotoxicity severely compromises male fertility, yet effective interventions remain limited. Building on our previous finding that yam protein (YP) modulates the gut-microbiota axis, this study investigated its direct protective role against cyclophosphamide (CTX)-induced testicular injury. Spectral analysis revealed a protein fraction (L-YP) with strong intrinsic fluorescence and optimal cytoprotection against oxidative stress. Proteomic characterization revealed six dominant proteins (YP1\u2013YP6). In vivo experiments demonstrated that L-YP upregulates the expression of tight junction proteins Occludin and ZO-1, restores hormone levels, and modulates inflammatory factors, thereby enhancing the integrity of the blood\u2013testis barrier. Network pharmacology analysis and molecular docking predicted a potential binding affinity between key components such as YP2 and NF-\u03baB p65, which may provide a structural basis for their regulatory role. Further validation at the gene level indicated that YP can improve the local testicular immune microenvironment by modulating the classical TLR4\/MyD88\/NF-\u03baB inflammatory signaling pathway. These findings suggest that yam protein alleviates chemotherapy-induced testicular damage, potentially through barrier protection and anti-inflammatory mechanisms, indicating its promise as a dietary protective agent.<\/jats:p>","DOI":"10.3390\/molecules31091387","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T09:09:12Z","timestamp":1776935352000},"page":"1387","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Yam-Active Protein Protects Against Cyclophosphamide-Induced Testicular Injury by Suppressing Inflammatory Responses"],"prefix":"10.3390","volume":"31","author":[{"given":"Jiahong","family":"Lu","sequence":"first","affiliation":[{"name":"Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun 130117, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiwen","family":"Hao","sequence":"additional","affiliation":[{"name":"Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun 130117, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuting","family":"Song","sequence":"additional","affiliation":[{"name":"Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun 130117, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Fang","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Jilin University, Changchun 130062, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Boyuan","family":"Hu","sequence":"additional","affiliation":[{"name":"Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun 130117, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun 130117, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ge","family":"Hui","sequence":"additional","affiliation":[{"name":"Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun 130117, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2758-9236","authenticated-orcid":false,"given":"Yunfei","family":"Xie","sequence":"additional","affiliation":[{"name":"School of Food Science and Technology, Jiangnan University, Wuxi 214122, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Jilin Ginseng Academy, Changchun University of Chinese Medicine, Changchun 130117, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Lin, Y.R., Guan, Q.Y., Li, L.Y., Tang, Z.M., Zhang, Q., and Zhao, X.H. (2021). In Vitro Immuno-Modulatory Potentials of Purslane (Portulaca oleracea L.) Polysaccharides with a Chemical Selenylation. Foods, 11.","DOI":"10.3390\/foods11010014"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"138897","DOI":"10.1016\/j.foodchem.2024.138897","article-title":"Prospects of yam (Dioscorea) polysaccharides: Structural features, bioactivities and applications","volume":"446","author":"Zhang","year":"2024","journal-title":"Food Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"101121","DOI":"10.1016\/j.cofs.2023.101121","article-title":"Chinese yam (Dioscorea opposita) and its bioactive compounds: The beneficial effects on gut microbiota and gut health","volume":"55","author":"Chang","year":"2024","journal-title":"Curr. Opin. Food Sci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"113798","DOI":"10.1016\/j.fct.2023.113798","article-title":"Dietary phytoestrogen diosgenin interrupts metabolism, physiology, and reproduction of Swiss albino mice: Possible mode of action as an emerging environmental contaminant, endocrine disruptor and reproductive toxicant","volume":"176","author":"Khushboo","year":"2023","journal-title":"Food Chem. Toxicol. Int. J. Publ. Br. Ind. Biol. Res. Assoc."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"113223","DOI":"10.1016\/j.jep.2020.113223","article-title":"The cold-soaking extract of Chinese yam (Dioscorea opposita Thunb.) protects against erectile dysfunction by ameliorating testicular function in hydrocortisone-induced KDS-Yang rats and in oxidatively damaged TM3 cells","volume":"263","author":"Yu","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"3575016","DOI":"10.1155\/2021\/3575016","article-title":"A Protein from Dioscorea polystachya (Chinese Yam) Improves Hydrocortisone-Induced Testicular Dysfunction by Alleviating Leydig Cell Injury via Upregulation of the Nrf2 Pathway","volume":"2021","author":"Yu","year":"2021","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_7","first-page":"179","article-title":"Current perspectives on the Nutrient composition and health benefits of yams (Discorea species)","volume":"5","author":"Ojimelukwe","year":"2021","journal-title":"Int. J. Agric. Environ. Food Sci."},{"key":"ref_8","first-page":"12","article-title":"Cancer statistics, 2024","volume":"74","author":"Siegel","year":"2024","journal-title":"CA Cancer J. Clin."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1038\/s41419-021-04221-6","article-title":"Src acts as the target of matrine to inhibit the proliferation of cancer cells by regulating phosphorylation signaling pathways","volume":"12","author":"Zhang","year":"2021","journal-title":"Cell Death Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.cjph.2020.04.012","article-title":"Molecular dynamics simulations on chitosan\/graphene nanocomposites as anticancer drug delivery using systems","volume":"66","author":"Shariatinia","year":"2020","journal-title":"Chin. J. Phys."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"195","DOI":"10.4103\/mgr.MEDGASRES-D-24-00074","article-title":"Effects of ozone treatment on chemotherapy-induced peripheral neuropathy: A promising research area","volume":"15","author":"Clavo","year":"2025","journal-title":"Med. Gas Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"120007","DOI":"10.1016\/j.jep.2025.120007","article-title":"Millettia speciosa Champ. Leguminosae ameliorates testicular damage in mice by repairing of blood-testis barrier dysfunction and testosterone synthesis","volume":"350","author":"Ai","year":"2025","journal-title":"J. Ethnopharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"100109","DOI":"10.1016\/j.jnim.2020.100109","article-title":"Antioxidant potential of garlic oil supplementation prevents cyclophosphamide-induced oxidative testicular damage and endocrine depletion in rats","volume":"18","author":"Famurewa","year":"2019","journal-title":"J. Nutr. Intermed. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Khamis, T., Hegazy, A.A., El-Fatah, S.S.A., Abdelfattah, E.R., Abdelfattah, M.M.M., Fericean, L.M., and Arisha, A.H. (2023). Hesperidin Mitigates Cyclophosphamide-Induced Testicular Dysfunction via Altering the Hypothalamic Pituitary Gonadal Axis and Testicular Steroidogenesis, Inflammation, and Apoptosis in Male Rats. Pharmaceuticals, 16.","DOI":"10.3390\/ph16020301"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"529","DOI":"10.4103\/mgr.MEDGASRES-D-24-00153","article-title":"Hyperbaric oxygen therapy for male infertility: A systematic review and meta-analysis on improving sperm quality and fertility outcomes","volume":"15","author":"Liu","year":"2025","journal-title":"Med. Gas Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"135415","DOI":"10.1016\/j.ijbiomac.2024.135415","article-title":"Yam protein ameliorates cyclophosphamide-induced intestinal immunosuppression by regulating gut microbiota and its metabolites","volume":"279","author":"Lu","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"8363","DOI":"10.1021\/acs.jafc.8b02407","article-title":"Fabrication and Characterization of Quinoa Protein Nanoparticle-Stabilized Food-Grade Pickering Emulsions with Ultrasound Treatment: Effect of Ionic Strength on the Freeze-Thaw Stability","volume":"66","author":"Qin","year":"2018","journal-title":"J. Agric. Food Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"108733","DOI":"10.1016\/j.foodhyd.2023.108733","article-title":"Schiff base type casein-konjac glucomannan conjugates with improved stability and emulsifying properties via mild covalent cross-linking","volume":"141","author":"Kuang","year":"2023","journal-title":"Food Hydrocoll."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.3390\/cells11101690","article-title":"Activation of MT1\/MT2 to Protect Testes and Leydig Cells against Cisplatin-Induced Oxidative Stress through the SIRT1\/Nrf2 Signaling Pathway","volume":"11","author":"Zhang","year":"2022","journal-title":"Cells"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1007\/BF03345805","article-title":"Growth hormone, prolactin, and sexuality","volume":"35","author":"Galdiero","year":"2012","journal-title":"J. Endocrinol. Investig."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"117260","DOI":"10.1016\/j.jep.2023.117260","article-title":"Protective effect of Huangqi-Guizhi-Wuwutang against cyclophosphamide-induced spermatogenesis dysfunction in mice by promoting steroid hormone biosynthesis","volume":"319","author":"Zhao","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"ref_22","first-page":"711","article-title":"Cyclophosphamide-induced testicular toxicity ameliorate by American ginseng treatment: An experimental study","volume":"16","author":"Hosseini","year":"2018","journal-title":"Int. J. Reprod. Biomed."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"121706","DOI":"10.1016\/j.jhazmat.2019.121706","article-title":"Cyanidin-3-O-glucoside restores spermatogenic dysfunction in cadmium-exposed pubertal mice via histone ubiquitination and mitigating oxidative damage","volume":"387","author":"Li","year":"2020","journal-title":"J. Hazard. Mater."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"18780","DOI":"10.1021\/acs.jafc.3c05900","article-title":"Phenolic Constituents from Black Quinoa Alleviate Insulin Resistance in HepG2 Cells via Regulating IRS1\/PI3K\/Akt\/GLUTs Signaling Pathways","volume":"71","author":"Cao","year":"2023","journal-title":"J. Agric. Food Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"16696","DOI":"10.1073\/pnas.0506084102","article-title":"Androgens regulate the permeability of the blood-testis barrier","volume":"102","author":"Meng","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1016\/j.joim.2019.07.002","article-title":"Cyclophosphamide-induced reproductive toxicity: Beneficial effects of Helichrysum odoratissimum (Asteraceae) in male Wistar rats","volume":"17","author":"Watcho","year":"2019","journal-title":"J. Integr. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"108674","DOI":"10.1016\/j.reprotox.2024.108674","article-title":"Effect of Humanin and MOTS-c on ameliorating reproductive damage induced by prepubertal cyclophosphamide chemotherapy in male mice","volume":"129","author":"Wang","year":"2024","journal-title":"Reprod. Toxicol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Jiao, W., Sang, Y., Wang, X., and Wang, S. (2023). Effects of 6-Shogaol on Glucose Uptake and Intestinal Barrier Integrity in Caco-2 Cells. Foods, 12.","DOI":"10.3390\/foods12030503"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"32173","DOI":"10.1038\/srep32173","article-title":"Role of IL-17 Pathways in Immune Privilege: A RNA Deep Sequencing Analysis of the Mice Testis Exposure to Fluoride","volume":"6","author":"Huo","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"17023","DOI":"10.1038\/sigtrans.2017.23","article-title":"NF-\u03baB signaling in inflammation","volume":"2","author":"Liu","year":"2017","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1146\/annurev.immunol.18.1.621","article-title":"Phosphorylation meets ubiquitination: The control of NF-\u03baB activity","volume":"18","author":"Karin","year":"2000","journal-title":"Annu. Rev. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6853","DOI":"10.1038\/sj.onc.1203239","article-title":"Activators and target genes of Rel\/NF-\u03baB transcription factors","volume":"18","author":"Pahl","year":"1999","journal-title":"Oncogene"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"111937","DOI":"10.1016\/j.fct.2020.111937","article-title":"Allicin alleviated acrylamide-induced NLRP3 inflammasome activation via oxidative stress and endoplasmic reticulum stress in Kupffer cells and SD rats liver","volume":"148","author":"Nan","year":"2021","journal-title":"Food Chem. Toxicol. Int. J. Publ. Br. Ind. Biol. Res. Assoc."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.ultsonch.2012.07.011","article-title":"Acid-induced gelation behavior of soybean protein isolate with high intensity ultrasonic pre-treatments","volume":"20","author":"Hu","year":"2013","journal-title":"Ultrason. Sonochem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"139387","DOI":"10.1016\/j.ijbiomac.2024.139387","article-title":"An active protein from Dendrobium officinale residue: Protects the gastric mucosa and stabilized in the gastrointestinal tract","volume":"294","author":"Pan","year":"2025","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"100175","DOI":"10.1016\/j.fochx.2021.100175","article-title":"Structural properties, antioxidant and immune activities of low molecular weight peptides from soybean dregs (Okara)","volume":"12","author":"Fang","year":"2021","journal-title":"Food Chem. X"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"112377","DOI":"10.1016\/j.foodres.2022.112377","article-title":"Changes in structural and functional properties of whey protein cross-linked by polyphenol oxidase","volume":"164","author":"Yang","year":"2023","journal-title":"Food Res. Int."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.softx.2015.06.001","article-title":"GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers","volume":"1\u20132","author":"Abraham","year":"2015","journal-title":"SoftwareX"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"H732","DOI":"10.1152\/ajpheart.00948.2011","article-title":"TLR4 regulates cardiac lipid accumulation and diabetic heart disease in the nonobese diabetic mouse model of type 1 diabetes","volume":"303","author":"Dong","year":"2012","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Chang, Z.P., Deng, G.F., Shao, Y.Y., Xu, D., Zhao, Y.N., Sun, Y.F., Zhang, S.Q., Hou, R.G., and Liu, J.J. (2021). Shaoyao-Gancao Decoction Ameliorates the Inflammation State in Polycystic Ovary Syndrome Rats via Remodeling Gut Microbiota and Suppressing the TLR4\/NF-\u03baB Pathway. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.670054"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1128\/IAI.74.1.549-556.2006","article-title":"MyD88-dependent pathways mediate resistance to Cryptosporidium parvum infection in mice","volume":"74","author":"Rogers","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6959741","DOI":"10.1155\/2020\/6959741","article-title":"Corticosterone Inhibits LPS-Induced NLRP3 Inflammasome Priming in Macrophages by Suppressing Xanthine Oxidase","volume":"2020","author":"Wu","year":"2020","journal-title":"Mediat. Inflamm."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/9\/1387\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T09:09:53Z","timestamp":1776935393000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/31\/9\/1387"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,23]]},"references-count":42,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["molecules31091387"],"URL":"https:\/\/doi.org\/10.3390\/molecules31091387","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,23]]}}}