{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T01:05:01Z","timestamp":1790730301751,"version":"4.1.0"},"reference-count":47,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:00:00Z","timestamp":1760054400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32302791"],"award-info":[{"award-number":["32302791"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003392","name":"Natural Science Foundation of Fujian Province","doi-asserted-by":"crossref","award":["2024J01331"],"award-info":[{"award-number":["2024J01331"]}],"id":[{"id":"10.13039\/501100003392","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Research and Technology Program of Fujian Academy of Agricultural Sciences","award":["ZYTS202420"],"award-info":[{"award-number":["ZYTS202420"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Foods"],"abstract":"<jats:p>This study investigated the protective effects of Gardenia jasminoides Ellis polysaccharides (GP) on lipopolysaccharide (LPS)-induced immunosuppression and oxidative stress in mice and explored how GP modulates macrophage polarization through the TLR4\/NF-\u03baB signaling axis. The results showed that GP notably restored thymus and spleen indices in LPS-treated mice, markedly decreased the serum concentrations of malondialdehyde, and enhanced superoxide dismutase activity and total antioxidant capacity. In RAW 264.7 macrophage cultures, GP displayed immunostimulatory effects by improving phagocytic activity, promoting NO synthesis, and enhancing the secretion of pro-inflammatory cytokines, including IL-1\u03b2, IL-6, and TNF-\u03b1. These effects were observed in cells not pretreated with TAK-242 or PDTC; however, they were not observed in cells pretreated with these inhibitors. At 300 \u00b5g\/mL concentration, GP markedly enhanced the transcriptional levels of iNOS and cytokine genes. Protein analysis revealed significant upregulation of TLR4, MyD88, TRAF6, NF-\u03baB RelA\/p65, and phosphorylated p65. Fluorescence imaging confirmed the nuclear translocation of p65. Collectively, these findings indicated that GP reversed systemic immunosuppression and oxidative stress, offering foundational insights for developing natural immune regulators. The observed immunomodulatory properties of GP are likely mediated through the TLR4\/NF-\u03baB signaling pathway.<\/jats:p>","DOI":"10.3390\/foods14203455","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T09:45:01Z","timestamp":1760089501000},"page":"3455","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Investigating the Effects of Gardenia Polysaccharides on LPS-Induced Immune Injury in Mice and Exploring the Molecular Mechanisms Underlying Its Regulatory Effect on the Immune Function of Macrophages"],"prefix":"10.3390","volume":"14","author":[{"given":"Pingdong","family":"Lin","sequence":"first","affiliation":[{"name":"Institute of Animal Husbandry and Veterinary Medicine, Fujian Academy of Agricultural Sciences, Fuzhou 350013, China"},{"name":"Fujian Key Laboratory of Animal Genetics and Breeding, Fuzhou 350013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Yue","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry and Veterinary Medicine, Fujian Academy of Agricultural Sciences, Fuzhou 350013, China"},{"name":"Fujian Key Laboratory of Animal Genetics and Breeding, Fuzhou 350013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Xiang","sequence":"additional","affiliation":[{"name":"College of Life Sciences, Fujian Normal University, Fuzhou 350117, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry and Veterinary Medicine, Fujian Academy of Agricultural Sciences, Fuzhou 350013, China"},{"name":"Fujian Key Laboratory of Animal Genetics and Breeding, Fuzhou 350013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinzhu","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Animal Husbandry and Veterinary Medicine, Fujian Academy of Agricultural Sciences, Fuzhou 350013, China"},{"name":"Fujian Key Laboratory of Animal Genetics and Breeding, Fuzhou 350013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.freeradbiomed.2014.05.020","article-title":"Glutathione transferase omega 1 is required for the lipopolysaccharide-stimulated induction of NADPH oxidase 1 and the production of reactive oxygen species in macrophages","volume":"73","author":"Menon","year":"2014","journal-title":"Free Radic. Biol. Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Xue, H., Li, P., Bian, J., Gao, Y., Sang, Y., and Tan, J. (2022). Extraction, purification, structure, modification, and biological activity of traditional Chinese medicine polysaccharides: A review. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.1005181"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"100414","DOI":"10.1016\/j.fochx.2022.100414","article-title":"Polysaccharides from fungi: A review on their extraction, purification, structural features, and biological activities","volume":"15","author":"Wang","year":"2022","journal-title":"Food Chem. X"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/bs.pmbts.2019.03.003","article-title":"The structures and biological functions of polysaccharides from traditional Chinese herbs","volume":"163","author":"Zeng","year":"2019","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1007\/s12272-022-01393-3","article-title":"Astragalus polysaccharide: A review of its immunomodulatory effect","volume":"45","author":"Li","year":"2022","journal-title":"Arch. Pharm. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"127933","DOI":"10.1016\/j.foodchem.2020.127933","article-title":"Immunomodulatory activities of polysaccharides from Ganoderma on immune effector cells","volume":"340","author":"Ren","year":"2021","journal-title":"Food Chem."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Lin, P., Chen, L., Huang, X., Xiao, F., Fu, L., Jing, D., Wang, J., Zhang, H., Sun, L., and Wu, Y. (2022). Structural characteristics of polysaccharide GP2a in Gardenia jasminoides and its immunomodulatory effect on macrophages. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231911279"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/35092620","article-title":"Immune recognition. A new receptor for beta-glucans","volume":"413","author":"Brown","year":"2001","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1038\/nri3665","article-title":"Innate immunity to influenza virus infection","volume":"14","author":"Iwasaki","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Yin, M., Zhang, Y., and Li, H. (2019). Advances in research on immunoregulation of macrophages by plant polysaccharides. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00145"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1002\/jcp.24157","article-title":"Modulation of macrophage activation and programming in immunity","volume":"228","author":"Liu","year":"2013","journal-title":"J. Cell. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.jgr.2021.06.003","article-title":"A review of the immunomodulatory activities of polysaccharides isolated from Panax species","volume":"46","author":"Hu","year":"2022","journal-title":"J. Ginseng Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6425","DOI":"10.1002\/jcp.26429","article-title":"Macrophage plasticity, polarization, and function in health and disease","volume":"233","author":"Mohammadian","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1146\/annurev-pathmechdis-012418-012718","article-title":"Diversity, mechanisms, and significance of macrophage plasticity","volume":"15","author":"Locati","year":"2020","journal-title":"Annu. Rev. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/978-1-4939-7837-3_12","article-title":"Polarizing macrophages in vitro","volume":"1784","author":"Huang","year":"2018","journal-title":"Methods Mol. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s12276-022-00724-0","article-title":"Immunomodulatory functional foods and their molecular mechanisms","volume":"54","author":"Kim","year":"2022","journal-title":"Exp. Mol. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"117991","DOI":"10.1016\/j.carbpol.2021.117991","article-title":"Water-soluble polysaccharides from Pleurotus eryngii fruiting bodies, their activity and affinity for Toll-like receptor 2 and dectin-1","volume":"264","author":"Ellefsen","year":"2021","journal-title":"Carbohydr. Polym."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"131586","DOI":"10.1016\/j.foodchem.2021.131586","article-title":"Interaction between polysaccharides and toll-like receptor 4: Primary structural role, immune balance perspective, and 3D interaction model hypothesis","volume":"374","author":"Li","year":"2022","journal-title":"Food Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.carbpol.2014.01.056","article-title":"Sargassum fusiforme polysaccharide activates nuclear factor kappa-B (NF-\u03baB) and induces cytokine production via Toll-like receptors","volume":"105","author":"Chen","year":"2014","journal-title":"Carbohydr. Polym."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"120533","DOI":"10.1016\/j.carbpol.2022.120533","article-title":"Innate immune receptors co-recognition of polysaccharides initiates multi-pathway synergistic immune response","volume":"305","author":"Li","year":"2023","journal-title":"Carbohydr. Polym."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Glinski, A., Lima de Souza, T., Zablocki da Luz, J., Bezerra Junior, A.G., Camargo de Oliveira, C., de Oliveira Ribeiro, C.A., and Filipak Neto, F. (2021). Toxicological effects of silver nanoparticles and cadmium chloride in macrophage cell line (RAW 264.7): An in vitro approach. J. Trace Elem. Med. Biol., 68.","DOI":"10.1016\/j.jtemb.2021.126854"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3262","DOI":"10.1039\/C9FO00482C","article-title":"Protective effects of polysaccharides from Cordyceps gunnii mycelia against cyclophosphamide-induced immunosuppression to TLR4\/TRAF6\/NF-\u03baB signalling in BALB\/c mice","volume":"10","author":"Meng","year":"2019","journal-title":"Food Funct."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"106173","DOI":"10.1016\/j.intimp.2019.106173","article-title":"Poria cocos polysaccharides attenuated ox-LDL-induced inflammation and oxidative stress via ERK activated Nrf2\/HO-1 signaling pathway and inhibited foam cell formation in VSMCs","volume":"80","author":"Zhao","year":"2020","journal-title":"Int. Immunopharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1016\/j.intimp.2008.02.008","article-title":"Anti-tumor and immunomodulating activities of proteoglycans from mycelium of Phellinus nigricans and culture medium","volume":"8","author":"Li","year":"2008","journal-title":"Int. Immunopharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1002\/ame2.12262","article-title":"Research progress on the relationship between intestinal microecology and intestinal bowel disease","volume":"5","author":"Fu","year":"2022","journal-title":"Animal Model Exp. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1007\/s00484-019-01769-z","article-title":"Cellular antioxidant enzyme activity and biomarkers for oxidative stress are affected by heat stress","volume":"63","author":"Habashy","year":"2019","journal-title":"Int. J. Biometeorol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.ejmech.2015.04.040","article-title":"The role of antioxidants in the chemistry of oxidative stress: A review","volume":"97","author":"Pisoschi","year":"2015","journal-title":"Eur. J. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4471","DOI":"10.3168\/jds.2022-22727","article-title":"Invited review: From heat stress to disease-Immune response and candidate genes involved in cattle thermotolerance","volume":"106","author":"Lemal","year":"2023","journal-title":"J. Dairy Sci."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Zhou, L., Liu, Z., Wang, Z., Yu, S., Long, T., Zhou, X., and Bao, Y. (2017). Astragalus polysaccharides exerts immunomodulatory effects via TLR4-mediated MyD88-dependent signaling pathway in vitro and in vivo. Sci. Rep., 7.","DOI":"10.1038\/srep44822"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Feng, L., Shi, P., Zhao, L., Shang, M., Han, Y., Han, N., Liu, Z., Li, S., Zhai, J., and Yin, J. (2024). Structural characterization of polysaccharides from Panax ginseng C. A. Meyer root and their triggered potential immunoregulatory and radioprotective activities. Int. J. Biol. Macromol., 280.","DOI":"10.1016\/j.ijbiomac.2024.135993"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.ejphar.2015.04.057","article-title":"It is all about fluidity: Fatty acids and macrophage phagocytosis","volume":"785","author":"Schumann","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1146\/annurev-physiol-022516-034339","article-title":"Macrophage polarization","volume":"79","author":"Murray","year":"2017","journal-title":"Annu. Rev. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Mu\u00f1oz, J., Akhavan, N.S., Mullins, A.P., and Arjmandi, B.H. (2020). Macrophage polarization and osteoporosis: A review. Nutrients, 12.","DOI":"10.3390\/nu12102999"},{"key":"ref_34","first-page":"61","article-title":"Requirement of scavenger receptors for activation of the IRF-3\/IFN-\u03b2\/STAT-1 pathway in TLR4-mediated production of NO by LPS-activated macrophages","volume":"134\u2013135","author":"Oliveira","year":"2023","journal-title":"Nitric Oxide"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/j.ijbiomac.2019.08.174","article-title":"A polysaccharide isolated from the fruits of Physalis alkekengi L. induces RAW264.7 macrophages activation via TLR2 and TLR4-mediated MAPK and NF-\u03baB signaling pathways","volume":"140","author":"Yang","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Wu, J., Mo, J., Xiang, W., Shi, X., Guo, L., Li, Y., Bao, Y., and Zheng, L. (2023). Immunoregulatory effects of Tetrastigma hemsleyanum polysaccharide via TLR4-mediated NF-\u03baB and MAPK signaling pathways in Raw264.7 macrophages. Biomed. Pharmacother., 161.","DOI":"10.1016\/j.biopha.2023.114471"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Yang, B., Ma, J., Gu, H., Xu, Y., Long, M., Xu, T., Liu, M., Yin, H., and Xu, Q. (2025). Polysaccharides isolated from Ampelopsis grossedentata and their immunomodulatory activity. Int. J. Biol. Macromol., 286.","DOI":"10.1016\/j.ijbiomac.2024.138513"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Wang, Z., Dong, B., Feng, Z., Yu, S., and Bao, Y. (2015). A study on immunomodulatory mechanism of Polysaccharopeptide mediated by TLR4 signaling pathway. BMC Immunol., 16.","DOI":"10.1186\/s12865-015-0100-5"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4329","DOI":"10.1016\/j.ijbiomac.2020.09.035","article-title":"Immunomodulatory mechanism of a purified polysaccharide isolated from Isaria cicadae Miquel on RAW264.7 cells via activating TLR4-MAPK-NF-\u03baB signaling pathway","volume":"164","author":"Xu","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"118288","DOI":"10.1016\/j.carbpol.2021.118288","article-title":"Structural characterization and mechanisms of macrophage immunomodulatory activity of a pectic polysaccharide from Cucurbita moschata Duch","volume":"269","author":"Huang","year":"2021","journal-title":"Carbohydr. Polym."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.ijbiomac.2017.12.113","article-title":"Dectin-1 mediates the immunoenhancement effect of the polysaccharide from Dictyophora indusiata","volume":"109","author":"Deng","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Zhao, T., Yang, M., Ma, L., Liu, X., Ding, Q., Chai, G., Lu, Y., Wei, H., Zhang, S., and Ding, C. (2023). Structural modification and biological activity of polysaccharides. Molecules, 28.","DOI":"10.3390\/molecules28145416"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.ijbiomac.2017.02.028","article-title":"Immunomodulatory effects of an acetylated Cyclocarya paliurus polysaccharide on murine macrophages RAW264.7","volume":"98","author":"Liu","year":"2017","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Yang, S., Sun, J., Gu, D., Li, P., Yao, L., Shi, D., Guo, S., and Liu, C. (2021). Antioxidant activities of sulfated Codonopsis polysaccharides in acute oxidative stress. J. Food Biochem., 45.","DOI":"10.1111\/jfbc.13974"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"10913","DOI":"10.1021\/jf902589m","article-title":"Carboxymethylated beta-glucan derived from Poria cocos with biological activities","volume":"57","author":"Wang","year":"2009","journal-title":"J. Agric. Food Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.ijbiomac.2021.02.046","article-title":"Structure characterization and in vitro immunomodulatory activities of carboxymethyl pachymaran","volume":"178","author":"Liu","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1039\/C6FO01545J","article-title":"Immune enhancement effects and extraction optimization of polysaccharides from Citrus aurantium L. var. amara Engl","volume":"8","author":"Shen","year":"2017","journal-title":"Food Funct."}],"container-title":["Foods"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2304-8158\/14\/20\/3455\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:22:26Z","timestamp":1760242946000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2304-8158\/14\/20\/3455"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,10]]},"references-count":47,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["foods14203455"],"URL":"https:\/\/doi.org\/10.3390\/foods14203455","relation":{},"ISSN":["2304-8158"],"issn-type":[{"value":"2304-8158","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,10]]}}}