{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T11:33:23Z","timestamp":1786361603347,"version":"build-2736575974"},"reference-count":71,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T00:00:00Z","timestamp":1786147200000},"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":"publisher","award":["22167019"],"award-info":[{"award-number":["22167019"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["22167019"],"award-info":[{"award-number":["22167019"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"the Natural science Fund of Inner Mongolia Province","award":["2023LHMS03023"],"award-info":[{"award-number":["2023LHMS03023"]}]},{"name":"the Natural science fund of Inner Mongolia Medical University","award":["YKD2023MS076"],"award-info":[{"award-number":["YKD2023MS076"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Curr. Issues Mol. Biol.","CIMB"],"abstract":"<jats:p>The structural and immunomodulatory properties of arabinogalactan proteins (AGPs) from edible medicinal plants remain largely unexplored. Here, A homogenous AG-II-like arabinogalactan protein (CTSP-W2, 9862 Da) was isolated from Cynanchum thesioides via hot-water extraction, ethanol precipitation, and column chromatography. Its structure was thoroughly characterized by high-performance gel permeation chromatography (HPGPC), Fourier-transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR), Congo-red, scanning electron microscopy (SEM), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), methylation analysis. The mechanism of immune activity was examined using specific inhibitors, Western blotting, and molecular docking. It comprises galactose, arabinose, glucose, galacturonic acid, xylose, and 18 amino acids (asparagine-rich), with a backbone of \u21923,6)-Galp-(1\u2192 and \u21926)-Galp-(1\u2192. CTSP-W2 significantly enhanced macrophage proliferation, phagocytosis, and secretion of Nitric oxide (NO), Tumor necrosis factor-alpha (TNF-\u03b1), and Interleukin-6 (IL-6). Inhibitor assays showed that Toll-like receptor 4 (TLR4, TAK-242) and Toll-like receptor 9 (TLR9, E6446) antagonists markedly reduced CTSP-W2-induced TNF-\u03b1, IL-6, and NO in a dose-dependent manner, whereas Toll-like receptor 2 (TLR2) inhibition (C29) unexpectedly upregulated these mediators. Western blot revealed that CTSP-W2 upregulated TLR4 and TLR9 protein expression and increased phosphorylation of Inhibitor of nuclear factor kappa-B alpha (I\u03baB\u03b1), nuclear factor kappa B (NF-\u03baB p65), and p38, indicating activation of the TLR4\/9\u2013NF-\u03baB\u2013p38 mitogen-activated protein kinase (MAPK) signaling axis. Furthermore, Molecular docking analysis further indicated that CTSP-W2 forms extremely strong hydrogen-bonding and hydrophobic interactions with TLR4 through its galactose chains. This study elucidates the immunoregulatory mechanism of CTSP-W2 and establishes a molecular basis for arabinogalactan proteins as potential natural immunomodulators.<\/jats:p>","DOI":"10.3390\/cimb48080804","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T10:23:50Z","timestamp":1786357430000},"page":"804","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Characterization of a New AG-II-like Glycoprotein from Cynanchum thesioides (Freyn) K. Schum and Its Immunostimulatory Activity Through Activation of TLR4\/9-Mediated MAPK\/NF-\u03baB Signaling Pathways"],"prefix":"10.3390","volume":"48","author":[{"given":"Mu","family":"Dan","sequence":"first","affiliation":[{"name":"Department of Chemical and Biological Engineering, School of Engineering and Technology, National University of Mongolia, Ulaanbaatar 14201, Mongolia"},{"name":"College of Pharmacy, Inner Mongolia Medical University, Jinshan Development Zone, Hohhot 010110, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Inner Mongolia Medical University, Jinshan Development Zone, Hohhot 010110, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Ga","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Inner Mongolia Medical University, Jinshan Development Zone, Hohhot 010110, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenming","family":"Bai","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Inner Mongolia Medical University, Jinshan Development Zone, Hohhot 010110, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2526-5705","authenticated-orcid":false,"given":"Pengwei","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Basic Medicine, Inner Mongolia Medical University, Jinshan Development Zone, Hohhot 010110, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5550-507X","authenticated-orcid":false,"given":"Han","family":"Ge","sequence":"additional","affiliation":[{"name":"Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"},{"name":"State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruirui","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"},{"name":"State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4828-5327","authenticated-orcid":false,"given":"Surina","family":"Bo","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Inner Mongolia Medical University, Jinshan Development Zone, Hohhot 010110, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2003-7156","authenticated-orcid":false,"given":"Munkhtsetseg","family":"Baatar","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biological Engineering, School of Engineering and Technology, National University of Mongolia, Ulaanbaatar 14201, Mongolia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,8]]},"reference":[{"key":"ref_1","unstructured":"Editorial Committee of Zhonghua Bencao, and National Traditional Chinese Herb Administration (1977). Zhonghua Bencao, Science Press. (In Chinese)."},{"key":"ref_2","unstructured":"Fang, J. (2020). Effect of the Alternating Magnetic Field on Physiology and Biochemical Characteristics in Cynanchum thesioides (Freyn) K. Schum. [Master\u2019s Thesis, Inner Mongolia University of Science and Technology]."},{"key":"ref_3","first-page":"2202","article-title":"Antidiarrheal effects of different original medicinal materials of Mongolian medicine \u201cDugemunong\u201d and their impact on serum DAO and TNF-\u03b1","volume":"40","author":"Xi","year":"2017","journal-title":"Chin. Med. Mater."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"130161","DOI":"10.1016\/j.ijbiomac.2024.130161","article-title":"Structural characterization of a glycoprotein from white jade snails (Achatina fulica) and its wound healing activity","volume":"263","author":"Li","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1016\/j.ijbiomac.2022.07.023","article-title":"A glycoprotein from mountain cultivated ginseng: Insights into their chemical characteristics and intracellular antioxidant activity","volume":"217","author":"Zhang","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_6","first-page":"1","article-title":"Progress on chemical constituents of Trametes versicolor glycopeptides","volume":"40","author":"Zhang","year":"2021","journal-title":"Edible Fungi China"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"139687","DOI":"10.1016\/j.ijbiomac.2025.139687","article-title":"Cirsii herba glycoprotein promotes macrophage M1 polarization through MAPK and NF-\u03baB signaling pathways via interaction with TLR4","volume":"296","author":"Zhao","year":"2025","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_8","first-page":"215","article-title":"Purification, structural characterization and immunomodulatory activity of natto polysaccharide-protein complexes","volume":"36","author":"Shen","year":"2015","journal-title":"Food Sci."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Duan, T., Du, Y., Xing, C., Wang, H.Y., and Wang, R.F. (2022). Toll-like receptor signaling and its role in cell-mediated immunity. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.812774"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1016\/j.ijbiomac.2019.09.158","article-title":"Structural characterization of arabinogalactan extracted from Ixeris chinensis (Thunb.) Nakai and its immunomodulatory effect on RAW264.7 macrophages","volume":"143","author":"Li","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.jff.2018.11.025","article-title":"An arabinogalactan isolated from Boswellia carterii: Purification, structural elucidation and macrophage stimulation via NF-\u03baB and MAPK pathways","volume":"52","author":"Bahramzadeh","year":"2019","journal-title":"J. Funct. Foods"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"104091","DOI":"10.1016\/j.jff.2020.104091","article-title":"Characterization of an arabinogalactan from the fruit hulls of Ficus pumila Linn. and its immunomodulatory effect","volume":"73","author":"Wu","year":"2020","journal-title":"J. Funct. Foods"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"123816","DOI":"10.1016\/j.ijbiomac.2023.123816","article-title":"Structural characterization and immunomodulatory activity of an arabinogalactan from Jasminum sambac (L.) Aiton tea processing waste","volume":"235","author":"Huang","year":"2023","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3859856","DOI":"10.1155\/2017\/3859856","article-title":"Cynanchum wilfordii polysaccharides suppress dextran sulfate sodium-induced acute colitis in mice and the production of inflammatory mediators from macrophages","volume":"2017","author":"Cho","year":"2017","journal-title":"Mediators Inflamm."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"124142","DOI":"10.1016\/j.ijbiomac.2023.124142","article-title":"Purification, structure identification and immune activity of a neutral polysaccharide from Cynanchum auriculatum","volume":"237","author":"Wang","year":"2023","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.ijbiomac.2021.11.172","article-title":"Structure characterization of an arabinogalactan from Cynanchum atratum and its immune stimulatory activity on RAW264.7 cells","volume":"194","author":"Li","year":"2022","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1038\/s44222-024-00193-2","article-title":"Engineered polysaccharides for controlling innate and adaptive immune responses","volume":"2","author":"Nam","year":"2024","journal-title":"Nat. Rev. Bioeng."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Wang, B., Wu, B., Ma, Y., Li, X., Zhang, Z., Liu, Y., and Chen, H. (2025). Astragalus polysaccharides: Structure-immunomodulation relationships, multi-target pharmacological activities, and cutting-edge applications in immune modulation. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1714898"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Oliveira-Nascimento, L., Massari, P., and Wetzler, L.M. (2012). The role of TLR2 in infection and immunity. Front. Immunol., 3.","DOI":"10.3389\/fimmu.2012.00079"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.ijbiomac.2020.06.270","article-title":"Purification and characterization of non-enzymatic glycoprotein (NEGp) from flax seed buffer extract that exhibits anticoagulant and antiplatelet activity","volume":"163","author":"Nandish","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_21","first-page":"51","article-title":"Structure, immunomodulatory, and antioxidant activities in vitro of polysaccharides from Radix asparagi","volume":"22","author":"Mu","year":"2022","journal-title":"J. Chin. Inst. Food Sci. Technol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Usoltseva, R.V., Zueva, A.O., Malyarenko, O.S., Anastyuk, S.D., Moiseenko, O.P., Isakov, V.V., Kusaykin, M.I., Jia, A., and Ermakova, S.P. (2023). Structure and metabolically oriented efficacy of fucoidan from brown alga Sargassum muticum in the model of colony formation of melanoma and breast cancer cells. Mar. Drugs, 21.","DOI":"10.3390\/md21090486"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Sun, M.G., Chen, J.J., Xu, J.M., Chen, W., Chen, X.B., and Yang, D.S. (2025). The chemical profiling and immunological activity of polysaccharides from the rhizome of Imperata cylindrica using hot water extraction. Molecules, 30.","DOI":"10.3390\/molecules30122635"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Qu, D., Lian, S., Hu, H., Sun, W., and Si, H. (2022). Characterization and macrophages immunomodulatory activity of two water-soluble polysaccharides from Abrus cantoniensis. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.969512"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"192","DOI":"10.4103\/2045-9912.273957","article-title":"Nitric oxide detection methods in vitro and in vivo","volume":"9","author":"Goshi","year":"2019","journal-title":"Med. Gas Res."},{"key":"ref_26","first-page":"5704","article-title":"Inhibition of TLR2 signaling by a small molecule inhibitor","volume":"194","author":"Mistry","year":"2015","journal-title":"J. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1124\/mol.105.019695","article-title":"A novel cyclohexene derivative, TAK-242, selectively inhibits Toll-like receptor 4-mediated cytokine production through suppression of intracellular signaling","volume":"69","author":"Ii","year":"2006","journal-title":"Mol. Pharmacol."},{"key":"ref_28","first-page":"15569","article-title":"Inhibitors of TLR9 signaling reveal a role for TLR9 in immune activation","volume":"107","author":"Duramad","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"139564","DOI":"10.1016\/j.molstruc.2024.139564","article-title":"Extraction and structural analysis of polysaccharides from Shatian pomelo peel","volume":"1318","author":"Lin","year":"2024","journal-title":"J. Mol. Struct."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1186\/s12964-024-01540-x","article-title":"Metabolism of asparagine in the physiological state and cancer","volume":"22","author":"Yuan","year":"2024","journal-title":"Cell Commun. Signal."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.molcel.2014.08.018","article-title":"Asparagine plays a critical role in regulating cellular adaptation to glutamine depletion","volume":"56","author":"Zhang","year":"2014","journal-title":"Mol. Cell"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"113591","DOI":"10.1016\/j.foodres.2023.113591","article-title":"Purification and characterization of a glycoprotein from Sipunculus nudus and its immune-enhancing activity to RAW 264.7 macrophages","volume":"174","author":"Lu","year":"2023","journal-title":"Food Res. Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"123710","DOI":"10.1016\/j.carbpol.2025.123710","article-title":"Pectin-type polysaccharides from raspberry (Rubus idaeus L.): Structure characterization and activity against DSS-induced colitis","volume":"364","author":"Dou","year":"2025","journal-title":"Carbohydr. Polym."},{"key":"ref_34","unstructured":"Goormaghtigh, E. (2021). Analysis of glycoproteins by ATR-FTIR spectroscopy: Comparative assessment. Mass Spectrometry of Glycoproteins: Methods and Protocols, Springer."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Qiu, Z., Zhang, M., Du, H., Wang, Y., Shao, X., Fu, J., and Wang, C. (2025). A sponge-like polysaccharide from pine pollen: Structural features and therapeutic potential in DNCB-induced atopic dermatitis models. Pharmaceutics, 17.","DOI":"10.3390\/pharmaceutics17081058"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"125671","DOI":"10.1016\/j.foodchem.2019.125671","article-title":"Purification, characterization, and functional properties of a novel glycoprotein from tartary buckwheat (Fagopyrum tartaricum) seed","volume":"309","author":"Zhou","year":"2020","journal-title":"Food Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"4642","DOI":"10.1002\/jps.22695","article-title":"Applications of circular dichroism (CD) for structural analysis of proteins: Qualification of near- and far-UV CD for protein higher order structural analysis","volume":"100","author":"Li","year":"2011","journal-title":"J. Pharm. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1038\/s42003-023-05178-2","article-title":"DichroIDP: A method for analyses of intrinsically disordered proteins using circular dichroism spectroscopy","volume":"6","author":"Miles","year":"2023","journal-title":"Commun. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Yang, W., Cheng, S., Liu, M., Li, N., Wang, J., Yao, W., and Gong, P. (2023). Lipid-lowering effects of a novel polysaccharide obtained from Fuzhuan brick tea in vitro. Foods, 12.","DOI":"10.3390\/foods12183428"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"117850","DOI":"10.1016\/j.lwt.2025.117850","article-title":"Novelly quantitative analysis on mixtures of food supplements containing amino acids via high-resolution pure shift 1H NMR spectroscopy","volume":"224","author":"Ma","year":"2025","journal-title":"LWT"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1039\/C6FO00089D","article-title":"Structural analysis and immunostimulatory activity of glycopeptides from Paecilomyces sinensis","volume":"7","author":"Zhu","year":"2016","journal-title":"Food Funct."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1016\/j.tetasy.2009.05.038","article-title":"Fast enantioselective amino acid quantitative 13C NMR determination by a praseodymium chiral shift reagent","volume":"20","author":"Arnaud","year":"2009","journal-title":"Tetrahedron Asymmetry"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1016\/j.tetasy.2010.06.033","article-title":"Synthesis of partially benzylated arabinofuranosides, NMR analysis, and application to oligosaccharide synthesis","volume":"21","author":"Plaza","year":"2010","journal-title":"Tetrahedron Asymmetry"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3307","DOI":"10.1016\/0031-9422(92)83678-R","article-title":"NMR spectroscopy in the structural elucidation of oligosaccharides and glycosides","volume":"31","author":"Agrawal","year":"1992","journal-title":"Phytochemistry"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Cui, S.W. (2005). Food Carbohydrates: Chemistry, Physical Properties, and Applications, CRC Press.","DOI":"10.1201\/9780203485286"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1016\/j.carbpol.2013.06.079","article-title":"Structural characterization and antitumor activity of a pectic polysaccharide from Codonopsis pilosula","volume":"98","author":"Yang","year":"2013","journal-title":"Carbohydr. Polym."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"124822","DOI":"10.1016\/j.carbpol.2025.124822","article-title":"Structure characteristics of a pectic polysaccharide from the leaves of Cornus officinalis Sieb. et Zucc. (Shanzhuyu) and its inhibition on hepatocellular carcinoma","volume":"376","author":"Gao","year":"2026","journal-title":"Carbohydr. Polym."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"125020","DOI":"10.1016\/j.carbpol.2026.125020","article-title":"Structural characterization of Taiwanofungus camphoratus polysaccharide and its ameliorative effects on myelosuppression and immunosuppression by regulating macrophage activation","volume":"379","author":"Wang","year":"2026","journal-title":"Carbohydr. Polym."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"137890","DOI":"10.1016\/j.ijbiomac.2024.137890","article-title":"Structural characterization of a polysaccharide from Scutellaria baicalensis Georgi and its immune-enhancing properties on RAW264.7 cells","volume":"283","author":"Xiong","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"110290","DOI":"10.1016\/j.foodres.2021.110290","article-title":"A review of NMR analysis in polysaccharide structure and conformation: Progress, challenge and perspective","volume":"143","author":"Yao","year":"2021","journal-title":"Food Res. Int."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/s41392-023-01452-1","article-title":"Macrophages in immunoregulation and therapeutics","volume":"8","author":"Chen","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Luo, M., Zhao, F., Cheng, H., Su, M., and Wang, Y. (2024). Macrophage polarization: An important role in inflammatory diseases. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1352946"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1136\/ard-2023-224878","article-title":"Proinflammatory phenotype of B10 and B10pro cells elicited by TNF-\u03b1 in rheumatoid arthritis","volume":"83","author":"Hu","year":"2024","journal-title":"Ann. Rheum. Dis."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BJ20090272","article-title":"Pathogen recognition in the innate immune response","volume":"420","author":"Kumar","year":"2009","journal-title":"Biochem. J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"115","DOI":"10.26599\/FSHW.2022.9250009","article-title":"Sulfated Cyclocarya paliurus polysaccharides exert immunomodulatory potential on macrophages via Toll-like receptor 4 mediated MAPK\/NF-\u03baB signaling pathways","volume":"13","author":"Yu","year":"2024","journal-title":"Food Sci. Hum. Wellness"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"132574","DOI":"10.1016\/j.ijbiomac.2024.132574","article-title":"Glycoprotein from Sargassum fusiforme exhibiting anti-inflammatory responses in vitro and in vivo via modulation of TLR4\/MyD88 and NF-\u03baB signaling","volume":"272","author":"Javed","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"107018","DOI":"10.1016\/j.jff.2025.107018","article-title":"Anoectochilus roxburghii polysaccharide alleviates DSS-induced ulcerative colitis by modulating the MAPK\/NF-\u03baB signaling pathway and gut microbiota","volume":"133","author":"Chen","year":"2025","journal-title":"J. Funct. Foods"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"142985","DOI":"10.1016\/j.ijbiomac.2025.142985","article-title":"Flammulina velutipes polysaccharide exerts immunomodulatory function involving RSAD2 to regulate the NF-\u03baB\/MAPK signaling pathway in RAW264.7 macrophage cells and in mouse spleen cells","volume":"309","author":"Wang","year":"2025","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1038\/s41596-020-0312-x","article-title":"The HDOCK server for integrated protein\u2013protein docking","volume":"15","author":"Yan","year":"2020","journal-title":"Nat. Protoc."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.jff.2018.09.029","article-title":"Purification, structural characterization of an arabinogalactan from green gram (Vigna radiata) and its role in macrophage activation","volume":"50","author":"Ketha","year":"2018","journal-title":"J. Funct. Foods"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"101378","DOI":"10.1016\/j.tjnut.2026.101378","article-title":"Glycoproteins and Arabinogalactan Proteins: Emerging Functional Ingredients in Nutrition and Human Health","volume":"156","author":"Leszczuk","year":"2026","journal-title":"J. Nutr."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"120340","DOI":"10.1016\/j.carbpol.2022.120340","article-title":"Most of the rhamnogalacturonan-I from cultured Arabidopsis cell walls is covalently linked to arabinogalactan-protein","volume":"301","author":"Tan","year":"2023","journal-title":"Carbohydr. Polym."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1016\/j.jaci.2010.05.011","article-title":"Arabinogalactan isolated from cowshed dust extract protects mice from allergic airway inflammation and sensitization","volume":"126","author":"Peters","year":"2010","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1016\/j.ijbiomac.2022.12.320","article-title":"Review on the genus Polygonatum polysaccharides: Extraction, purification, structural characteristics and bioactivities","volume":"229","author":"Gong","year":"2023","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"100974","DOI":"10.1016\/j.jpha.2024.100974","article-title":"Structural characterization and mechanisms of macrophage immunomodulatory activity of a novel polysaccharide with a galactose backbone from the processed Polygonati Rhizoma","volume":"14","author":"Su","year":"2024","journal-title":"J. Pharm. Anal."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/intimm\/dxh186","article-title":"Toll-like receptors in innate immunity","volume":"17","author":"Takeda","year":"2005","journal-title":"Int. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0165-2478(02)00010-X","article-title":"Up-regulation of TLR9 gene expression by LPS in mouse macrophages via activation of NF-\u03baB, ERK and p38 MAPK signal pathways","volume":"81","author":"An","year":"2002","journal-title":"Immunol. Lett."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"8110","DOI":"10.4049\/jimmunol.0901031","article-title":"Signaling Crosstalk during Sequential TLR4 and TLR9 Activation Amplifies the Inflammatory Response of Mouse Macrophages","volume":"183","author":"Nguyen","year":"2009","journal-title":"J. Immunol."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Li, L., Chen, H., Huang, G., Lv, Y., Yao, L., Guo, Z., and Wei, C. (2024). Structure of polysaccharide from Dendrobium nobile Lindl. and its mode of action on TLR4 to exert immunomodulatory effects. Foods, 13.","DOI":"10.3390\/foods13091356"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1016\/j.phytochem.2010.05.021","article-title":"Structural characterization of laminaran and galactofucan extracted from the brown seaweed Saccharina longicruris","volume":"71","author":"Rioux","year":"2010","journal-title":"Phytochemistry"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"132931","DOI":"10.1016\/j.ijbiomac.2024.132931","article-title":"Screening of Poria cocos polysaccharide with immunomodulatory activity and its activation effects on TLR4\/MD2\/NF-\u03baB pathway","volume":"273","author":"Sun","year":"2024","journal-title":"Int. J. Biol. 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