{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:07:27Z","timestamp":1792800447352,"version":"4.5.0"},"reference-count":65,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,3,19]],"date-time":"2024-03-19T00:00:00Z","timestamp":1710806400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Foods"],"abstract":"<jats:p>The aim of this study was to explore the immunomodulatory effect of Polygonatum sibiricum saponin (PS) in a cyclophosphamide-induced (Cy) immunosuppression mice model. Oral administration of PS by gavage effectively alleviated weight loss caused by Cy and increased the index of immune organs. PS promoted the proliferation of splenic lymphocytes and T cell subsets (CD3+, CD355+, CD4+\/CD8+) and relieved the xylene-induced inflammatory response and Cy-induced increase of serum hemolysin. Moreover, PS increased serum levels of lactate dehydrogenase and acid phosphatase. PS elevated serum level of cytokines and immunoglobulins (TNF-\u03b1, IFN-\u03b3, IL-4, IL-6, IL-\u03b2, SIgA, and IgG) and the expression of mRNA of IL-10, TNF-\u03b1, and IL-6 in the spleen. Increased mRNA expression of tight junction protein (ZO-1, Mucin2, Occludin) expression and protein expression of IL-6\/MyD88\/TLR4 in the small intestine showed that PS exhibited a restorative effect on intestinal mucosal injury caused by cyclophosphamide. Oral PS prevented Cy-induced decline in leukocytes, red blood cells, lymphocytes, hemoglobin concentrations, and neutrophils, providing evidence for alleviating hematopoietic disorders. In addition, PS increased SOD and NO levels, reduced MDA levels, and improved oxidative damage in the liver. These findings demonstrate that PS has the potential to be developed as a supplemental agent for alleviating immunosuppression caused by chemotherapeutic agents.<\/jats:p>","DOI":"10.3390\/foods13060934","type":"journal-article","created":{"date-parts":[[2024,3,20]],"date-time":"2024-03-20T05:56:07Z","timestamp":1710914167000},"page":"934","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Polygonatum sibiricum Saponin Prevents Immune Dysfunction and Strengthens Intestinal Mucosal Barrier Function in Cyclophosphamide-Induced Immunosuppressed BALB\/c Mice"],"prefix":"10.3390","volume":"13","author":[{"given":"Dongyun","family":"Zhao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Marine Food Processing and Safety Control, National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huanhuan","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Marine Food Processing and Safety Control, National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunhong","family":"Yan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Marine Food Processing and Safety Control, National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Teng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Marine Food Processing and Safety Control, National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Marine Food Processing and Safety Control, National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomeng","family":"Ren","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Marine Food Processing and Safety Control, National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6336-2661","authenticated-orcid":false,"given":"Xiaodong","family":"Xia","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Marine Food Processing and Safety Control, National Engineering Research Center of Seafood, School of Food Science and Technology, Dalian Polytechnic University, Dalian 116034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1007\/s00280-016-3152-1","article-title":"The effect of cyclophosphamide on the immune system: Implications for clinical cancer therapy","volume":"78","author":"Ahlmann","year":"2016","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"109793","DOI":"10.1016\/j.foodres.2020.109793","article-title":"Bacillus coagulans 13002 and fructo-oligosaccharides improve the immunity of mice with immunosuppression induced by cyclophosphamide through modulating intestinal-derived and fecal microbiota","volume":"140","author":"Zhao","year":"2021","journal-title":"Food Res. Int."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"850066","DOI":"10.3389\/fphar.2022.850066","article-title":"TLRs-JNK\/ NF-\u03baB Pathway Underlies the Protective Effect of the Sulfide Salt against Liver Toxicity","volume":"13","author":"Heeba","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Awad, B., Hamza, A.A., Al-Maktoum, A., Al-Salam, S., and Amin, A. (2023). Combining Crocin and Sorafenib Improves Their Tumor-Inhibiting Effects in a Rat Model of Diethylnitrosamine-Induced Cirrhotic-Hepatocellular Carcinoma. Cancers, 15.","DOI":"10.3390\/cancers15164063"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S60","DOI":"10.1080\/10408398.2015.1069255","article-title":"Advances on Bioactive Polysaccharides from Medicinal Plants","volume":"56","author":"Xie","year":"2016","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"7062","DOI":"10.1038\/s41598-021-86391-z","article-title":"Camel whey protein hydrolysates induced G2\/M cellcycle arrest in human colorectal carcinoma","volume":"11","author":"Murali","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Bouabdallah, S., Al-Maktoum, A., and Amin, A. (2023). Steroidal Saponins: Naturally Occurring Compounds as Inhibitors of the Hallmarks of Cancer. Cancers, 15.","DOI":"10.3390\/cancers15153900"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Zheng, Y., Li, S., Li, C., Shao, Y., and Chen, A. (2022). Polysaccharides from Spores of Cordyceps cicadae Protect against Cyclophosphamide-Induced Immunosuppression and Oxidative Stress in Mice. Foods, 11.","DOI":"10.3390\/foods11040515"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1002\/JLB.2A0419-117R","article-title":"Ginsenoside Rh2 reverses cyclophosphamide-induced immune deficiency by regulating fatty acid metabolism","volume":"106","author":"Qian","year":"2019","journal-title":"J. Leukoc. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Wen, X., Peng, H., Zhang, H., He, Y., Guo, F., Bi, X., Liu, J., and Sun, Y. (2024). Wheat Bran Polyphenols Ameliorate DSS-Induced Ulcerative Colitis in Mice by Suppressing MAPK\/NF-\u03baB Inflammasome Pathways and Regulating Intestinal Microbiota. Foods, 13.","DOI":"10.3390\/foods13020225"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Chai, Y., Luo, J., and Bao, Y. (2021). Effects of Polygonatum sibiricum saponin on hyperglycemia, gut microbiota composition and metabolic profiles in type 2 diabetes mice. Biomed. Pharmacother., 143.","DOI":"10.1016\/j.biopha.2021.112155"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1186\/s41936-020-00177-9","article-title":"Dandelion prevents liver fibrosis, inflammatory response, and oxidative stress in rats","volume":"81","author":"Hamza","year":"2020","journal-title":"J. Basic Appl. Zool."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Koboziev, I., Scoggin, S., Gong, X., Mirzaei, P., Zabet-Moghaddam, M., Yosofvand, M., Moussa, H., Jones-Hall, Y., and Moustaid-Moussa, N. (2020). Effects of Curcumin in a Mouse Model of Very High Fat Diet-Induced Obesity. Biomolecules, 10.","DOI":"10.3390\/biom10101368"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1211\/jpp.59.8.0017","article-title":"Separation and purification of saponins from Semen Ziziphus jujuba and their sedative and hypnotic effects","volume":"59","author":"Jiang","year":"2007","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Hu, X., Lin, L., Ding, G., and Yu, F. (2019). Immunomodulatory Activity of Low Molecular-Weight Peptides from Nibea japonica in RAW264.7 Cells via NF-\u03baB Pathway. Mar. Drugs, 17.","DOI":"10.3390\/md17070404"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.ijbiomac.2022.12.142","article-title":"A polysaccharide from Pleurotus citrinopileatus mycelia enhances the immune response in cyclophosphamide-induced immunosuppressed mice via p62\/Keap1\/Nrf2 signal transduction pathway","volume":"228","author":"Meng","year":"2023","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"264","DOI":"10.2174\/1389200219666180129125436","article-title":"Herbal Immunomodulators\u2014A Remedial Panacea for Designing and Developing Effective Drugs and Medicines: Current Scenario and Future Prospects","volume":"19","author":"Tiwari","year":"2018","journal-title":"Curr. Drug Metab."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Guan, Q.Y., Lin, Y.R., Li, L.Y., Tang, Z.M., Zhao, X.H., and Shi, J. (2021). In Vitro Immunomodulation of the Polysaccharides from Yam (Dioscorea opposita Thunb.) in Response to a Selenylation of Lower Extent. Foods, 10.","DOI":"10.3390\/foods10112788"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1186\/1742-2094-7-97","article-title":"Immunomodulatory effect of Hawthorn extract in an experimental stroke model","volume":"7","author":"Elango","year":"2010","journal-title":"J. Neuroinflamm."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.carbpol.2007.04.012","article-title":"Structural investigation of two neutral polysaccharides isolated from rhizome of Polygonatum sibiricum","volume":"70","author":"Liu","year":"2007","journal-title":"Carbohydr. Polym."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1080\/10286020.2018.1478815","article-title":"Steroidal saponins from the rhizome of Polygonatum sibiricum","volume":"21","author":"Tang","year":"2019","journal-title":"J. Asian Nat. Prod. Res."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Gu, W., Wang, Y., Zeng, L., Dong, J., Bi, Q., Yang, X., Che, Y., He, S., and Yu, J. (2020). Polysaccharides from Polygonatum kingianum improve glucose and lipid metabolism in rats fed a high fat diet. Biomed. Pharmacother., 125.","DOI":"10.1016\/j.biopha.2020.109910"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2566917","DOI":"10.1155\/2022\/2566917","article-title":"Polysaccharides from Polygonatum cyrtonema Hua Reduce Depression-Like Behavior in Mice by Inhibiting Oxidative Stress-Calpain-1-NLRP3 Signaling Axis","volume":"2022","author":"Shen","year":"2022","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1181861","DOI":"10.3389\/fpls.2023.1181861","article-title":"Metabolome and transcriptome signatures shed light on the anti-obesity effect of Polygonatum sibiricum","volume":"14","author":"Ou","year":"2023","journal-title":"Front. Plant Sci."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Xie, Y., Jiang, Z., Yang, R., Ye, Y., Pei, L., Xiong, S., Wang, S., Wang, L., and Liu, S. (2021). Polysaccharide-rich extract from Polygonatum sibiricum protects hematopoiesis in bone marrow suppressed by triple negative breast cancer. Biomed. Pharmacother., 137.","DOI":"10.1016\/j.biopha.2021.111338"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"391065","DOI":"10.1155\/2015\/391065","article-title":"Hypolipidemic Activity and Antiatherosclerotic Effect of Polysaccharide of Polygonatum sibiricum in Rabbit Model and Related Cellular Mechanisms","volume":"2015","author":"Yang","year":"2015","journal-title":"Evid.-Based Complement. Altern. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2187","DOI":"10.1080\/10717544.2021.1977422","article-title":"Network pharmacology and experimental investigation of Rhizoma polygonati extract targeted kinase with herbzyme activity for potent drug delivery","volume":"28","author":"Xie","year":"2021","journal-title":"Drug Deliv."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Qi, Z., Chen, L., Li, Z., Shao, Z., Qi, Y., Gao, K., Liu, S., Sun, Y., Li, P., and Liu, J. (2019). Immunomodulatory Effects of (24R)-Pseudo-Ginsenoside HQ and (24S)-Pseudo-Ginsenoside HQ on Cyclophosphamide-Induced Immunosuppression and Their Anti-Tumor Effects Study. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20040836"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"110655","DOI":"10.1016\/j.fct.2019.110655","article-title":"Methyl protodioscin from Polygonatum sibiricum inhibits cervical cancer through cell cycle arrest and apoptosis induction","volume":"132","author":"Ma","year":"2019","journal-title":"Food Chem. Toxicol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"105855","DOI":"10.1016\/j.fitote.2024.105855","article-title":"Effect of Polygonatum sibiricum saponins on gut microbiota of mice with ulcerative colitis","volume":"174","author":"Cao","year":"2024","journal-title":"Fitoterapia"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.phytochem.2019.05.013","article-title":"Antiproliferative steroidal glycosides from rhizomes of Polygonatum sibiricum","volume":"164","author":"Zhou","year":"2019","journal-title":"Phytochemistry"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1080\/08923973.2021.1885043","article-title":"Immunomodulatory activity of puerarin in RAW264.7 macrophages and cyclophosphamide-induced immunosuppression mice","volume":"43","author":"Chang","year":"2021","journal-title":"Immunopharmacol. Immunotoxicol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Mao, R., Wu, L., Zhu, N., Liu, X., Liu, R., and Li, Y. (2019). Naked Oat (Avena nuda L.) Oligopeptides:Immunomodulatory Effects on Innate and AdaptiveImmunity in Mice via Cytokine Secretion, AntibodyProduction, and Th Cells Stimulation. Nutrients, 11.","DOI":"10.3390\/nu11040927"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3457","DOI":"10.1007\/s00018-011-0796-1","article-title":"Mechanisms of NK cell activation: CD4(+) T cells enter the scene","volume":"68","author":"Bihl","year":"2011","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ymeth.2006.07.020","article-title":"Use of SRBC antibody responses for immunotoxicity testing","volume":"41","author":"Ladics","year":"2007","journal-title":"Methods"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.ijbiomac.2008.06.004","article-title":"Studies of macrophage immuno-modulating activity of polysaccharides isolated from Paecilomyces tenuipes","volume":"43","author":"Chen","year":"2008","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_38","first-page":"3626879","article-title":"Activities of Some Medicinal Plants on the Proliferation and Invasion of Brain Tumor Cell Lines","volume":"2020","author":"Ngulde","year":"2020","journal-title":"Adv. Pharmacol. Pharm. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2222","DOI":"10.1039\/D0NA00958J","article-title":"Generation of particle assemblies mimicking enzymatic activity by processing of herbal food: The case of rhizoma polygonati and other natural ingredients in traditional Chinese medicine","volume":"3","author":"Benassi","year":"2021","journal-title":"Nanoscale Adv."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3566","DOI":"10.1039\/C6FO00667A","article-title":"Immunostimulatory activity of glycopeptides from Paecilomyces sinensis under normal and cyclophosphamide induced immunosuppressive conditions in mice models","volume":"7","author":"Zhu","year":"2016","journal-title":"Food Funct."},{"key":"ref_41","first-page":"2764","article-title":"Therapeutic effect of herb residue fermentation supernatant on spleen-deficient mice","volume":"17","author":"Zhao","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.imlet.2011.08.001","article-title":"Effective inhibition of a Strongylocentrotus nudus eggs polysaccharide against hepatocellular carcinoma is mediated via immunoregulation in vivo","volume":"141","author":"Wang","year":"2011","journal-title":"Immunol. Lett."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/j.carbpol.2015.09.079","article-title":"Characterization and immunoenhancement activities of Eucommia ulmoides polysaccharides","volume":"136","author":"Feng","year":"2016","journal-title":"Carbohydr. Polym."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1016\/j.clim.2014.05.010","article-title":"Evaluation of T and B lymphocyte function in clinical practice using a flow cytometry based proliferation assay","volume":"153","author":"Marits","year":"2014","journal-title":"Clin. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1111\/imr.12266","article-title":"Macrophage defense mechanisms against intracellular bacteria","volume":"264","author":"Weiss","year":"2015","journal-title":"Immunol. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1038\/s41392-018-0006-9","article-title":"miRNAs reshape immunity and inflammatory responses in bacterial infection","volume":"3","author":"Zhou","year":"2018","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"604981","DOI":"10.3389\/fimmu.2020.604981","article-title":"Long Non-coding RNAs RN7SK and GAS5 Regulate Macrophage Polarization and Innate Immune Responses","volume":"11","author":"Ahmad","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Monmai, C., You, S., and Park, W.J. (2019). Immune-enhancing effects of anionic macromolecules extracted from Codium fragile on cyclophosphamide-treated mice. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0211570"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1006\/bbrc.1996.0890","article-title":"Two-peak kinetic curve of the chemiluminescence in phorbol-induced macrophage","volume":"223","author":"Li","year":"1996","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1016\/j.intimp.2010.05.005","article-title":"Water-soluble polysaccharide obtained from Acorus calamus L. classically activates macrophages and stimulates Th1 response","volume":"10","author":"Belska","year":"2010","journal-title":"Int. Immunopharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1007\/s00441-015-2252-2","article-title":"Kupffer-cell-expressed transmembrane TNF-\u03b1 is a major contributor to lipopolysaccharide and D-galactosamine-induced liver injury","volume":"363","author":"Yang","year":"2016","journal-title":"Cell Tissue Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4350965","DOI":"10.1155\/2016\/4350965","article-title":"ROS and ROS-Mediated Cellular Signaling","volume":"2016","author":"Zhang","year":"2016","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2659","DOI":"10.1080\/21645515.2015.1082694","article-title":"Effects of Fuzheng Paidu tablet on peripheral blood T lymphocytes, intestinal mucosa T lymphocytes, and immune organs in cyclophosphamide-induced immunosuppressed mice","volume":"11","author":"Miao","year":"2015","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/j.micinf.2016.10.010","article-title":"IL-2 complex treatment amplifies CD8(+) T cell mediated immunity following herpes simplex virus-1 infection","volume":"18","author":"Rajasagi","year":"2016","journal-title":"Microbes Infect."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/0027-5107(89)90192-9","article-title":"Generation of oxy radicals in biosystems","volume":"214","author":"Simic","year":"1989","journal-title":"Mutat. Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1007\/s13105-015-0423-y","article-title":"Protective effect of centella triterpene saponins against cyclophosphamide-induced immune and hepatic system dysfunction in rats: Its possible mechanisms of action","volume":"71","author":"Duggina","year":"2015","journal-title":"J. Physiol. Biochem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.biocel.2006.07.001","article-title":"Free radicals and antioxidants in normal physiological functions and human disease","volume":"39","author":"Valko","year":"2007","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"110756","DOI":"10.1016\/j.foodres.2021.110756","article-title":"Sulfated modification enhances the immunomodulatory effect of Cyclocarya paliurus polysaccharide on cyclophosphamide-induced immunosuppressed mice through MyD88-dependent MAPK\/NF-\u03baB and PI3K-Akt signaling pathways","volume":"150","author":"Yu","year":"2021","journal-title":"Food Res. Int."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"342","DOI":"10.3389\/fimmu.2016.00342","article-title":"Development and Function of Secondary and Tertiary Lymphoid Organs in the Small Intestine and the Colon","volume":"7","author":"Buettner","year":"2016","journal-title":"Front. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1136\/gutjnl-2020-320777","article-title":"Cross-talk between the gut microbiota and monocyte-like macrophages mediates an inflammatory response to promote colitis-associated tumourigenesis","volume":"70","author":"Yang","year":"2020","journal-title":"Gut"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1007\/BF00915547","article-title":"The common mucosal immune system and current strategies for induction of immune responses in external secretions","volume":"7","author":"Mestecky","year":"1987","journal-title":"J. Clin. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"595700","DOI":"10.3389\/fimmu.2020.595700","article-title":"Effects of Polysaccharides from Auricularia auricula on the Immuno-Stimulatory Activity and Gut Microbiota in Immunosuppressed Mice Induced by Cyclophosphamide","volume":"11","author":"Kong","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.jcmgh.2020.04.001","article-title":"Tight Junctions as Targets and Effectors of Mucosal Immune Homeostasis","volume":"10","author":"Zuo","year":"2020","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"104057","DOI":"10.1016\/j.jff.2020.104057","article-title":"Effects of polysaccharides from bee collected pollen of Chinese wolfberry on immune response and gut microbiota composition in cyclophosphamide-treated mice","volume":"72","author":"Zhao","year":"2020","journal-title":"J. Funct. Foods"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"22539","DOI":"10.1074\/jbc.M314337200","article-title":"Akt kinase activation blocks apoptosis in intestinal epithelial cells by inhibiting caspase-3 after polyamine depletion","volume":"279","author":"Zhang","year":"2004","journal-title":"J. Biol. Chem."}],"container-title":["Foods"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2304-8158\/13\/6\/934\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:16:08Z","timestamp":1760105768000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2304-8158\/13\/6\/934"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,19]]},"references-count":65,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["foods13060934"],"URL":"https:\/\/doi.org\/10.3390\/foods13060934","relation":{},"ISSN":["2304-8158"],"issn-type":[{"value":"2304-8158","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,19]]}}}