Yam glycoprotein mediated the immunomodulation of macrophages by targeting TLR4.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Yam glycoprotein mediated the immunomodulation of macrophages by targeting TLR4.
Συγγραφείς: Luo Y; School of Pharmacy, Xi'an Jiaotong University, No. 76 Western Yanta Road, Xi'an City, 710061, Shaanxi Province, P.R. China., Wang S; School of Pharmacy, Xi'an Jiaotong University, No. 76 Western Yanta Road, Xi'an City, 710061, Shaanxi Province, P.R. China., Liu L; School of Pharmacy, Xi'an Jiaotong University, No. 76 Western Yanta Road, Xi'an City, 710061, Shaanxi Province, P.R. China., Zhu R; School of Pharmacy, Xi'an Jiaotong University, No. 76 Western Yanta Road, Xi'an City, 710061, Shaanxi Province, P.R. China., Wang X; School of Pharmacy, Xi'an Jiaotong University, No. 76 Western Yanta Road, Xi'an City, 710061, Shaanxi Province, P.R. China., Ma Y; School of Pharmacy, Xi'an Jiaotong University, No. 76 Western Yanta Road, Xi'an City, 710061, Shaanxi Province, P.R. China., Song H; School of Pharmacy, Xi'an Jiaotong University, No. 76 Western Yanta Road, Xi'an City, 710061, Shaanxi Province, P.R. China., Wen S; School of Pharmacy, Xi'an Jiaotong University, No. 76 Western Yanta Road, Xi'an City, 710061, Shaanxi Province, P.R. China., Li L; School of Pharmacy, Xi'an Jiaotong University, No. 76 Western Yanta Road, Xi'an City, 710061, Shaanxi Province, P.R. China., Xia S; School of Pharmacy, Xi'an Jiaotong University, No. 76 Western Yanta Road, Xi'an City, 710061, Shaanxi Province, P.R. China., Li W; School of Pharmacy, Xi'an Jiaotong University, No. 76 Western Yanta Road, Xi'an City, 710061, Shaanxi Province, P.R. China. liwf@mail.xjtu.edu.cn., Niu X; School of Pharmacy, Xi'an Jiaotong University, No. 76 Western Yanta Road, Xi'an City, 710061, Shaanxi Province, P.R. China. niuxf@mail.xjtu.edu.cn.
Πηγή: Molecular biology reports [Mol Biol Rep] 2026 Jun 18; Vol. 53 (1). Date of Electronic Publication: 2026 Jun 18.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Reidel Country of Publication: Netherlands NLM ID: 0403234 Publication Model: Electronic Cited Medium: Internet ISSN: 1573-4978 (Electronic) Linking ISSN: 03014851 NLM ISO Abbreviation: Mol Biol Rep Subsets: MEDLINE
Imprint Name(s): Original Publication: Dordrecht, Boston, Reidel.
Ιατρικοί όροι (MeSH): Macrophages*/drug effects , Macrophages*/immunology , Macrophages*/metabolism , Toll-Like Receptor 4*/metabolism , Dioscorea*/chemistry , Dioscorea*/metabolism , Immunomodulation*/drug effects , Glycoproteins*/pharmacology , Glycoproteins*/metabolism , Plant Proteins*/pharmacology, Reactive Oxygen Species/metabolism ; NF-kappa B/metabolism ; Signal Transduction/drug effects ; Cell Proliferation/drug effects ; Immunologic Factors/pharmacology ; Animals ; Mice ; RAW 264.7 Cells ; Toll-Like Receptor Agonists
Περίληψη: Background: Yam is a medicinal plant and previous studies have demonstrated that the yam glycoprotein (GLP1) possessed immunomodulatory bioactivity. However, how GLP1 exerted immunomodulatory effect and the molecular mechanism is unclear. To investigate the underlying mechanisms, the immunoregulation of GLP1 on macrophages are examined.
Methods and Results: The composition of GLP1 was investigated using high-performance liquid chromatography (HPLC) and UV visible spectrophotometer (UV-Vis). The activity of macrophages was detected, and the effects of GLP1 on macrophages were studied using immunofluorescence, flow cytometry, Enzyme-linked immunosorbent assay (ELISA), and Western blotting. Results indicated that GLP1, as a biomolecule, contained abundant monosaccharides and possessed O-glycopeptide bonds. GLP1 bound to pattern recognition receptors (PRRs) and was internalized by macrophages via toll-like receptor 4 (TLR4), thereby exerting its immunomodulatory effects. Further experimental studies revealed that GLP1 promoted RAW264.7 cells proliferation by advancing cells from G0/G1 phase to S phase. Additionally, GLP1 stimulated the secretion of reactive oxygen species (ROS) from mitochondria and induced macrophage polarization toward the M1 phenotype.
Conclusion: GLP1 is a functional protein and has the capacity to regulate macrophages immune responses via the TLR4/NF-κB pathway. The findings highlighted the potential of GLP1 might as a dietary immunostimulant at the molecular level.
(© 2026. The Author(s), under exclusive licence to Springer Nature B.V.)
Competing Interests: Declarations. Competing interests: The authors declare no competing interests.
References: Saeed A, Ruan XL, Guan HG et al (2020) Regulation of cGAS-Mediated Immune Responses and Immunotherapy. Adv Sci (Weinh) 7(6):1902599. https://doi.org/10.1002/advs.201902599. (PMID: 10.1002/advs.201902599321950867080523)
Kumar V (2020) Toll-like receptors in sepsis-associated cytokine storm and their endogenous negative regulators as future immunomodulatory targets. Int Immunopharmacol 89(Pt B) 107087. https://doi.org/10.1016/j.intimp.2020.
Merien F (2016) A Journey with Elie Metchnikoff: From innate cell mechanisms in infectious diseases to quantum biology. Front Public Health 4:125. https://doi.org/10.3389/fpubh.2016.00125. (PMID: 10.3389/fpubh.2016.00125273792274909730)
Chen Z, Tian RF, She ZG et al (2020) Role of oxidative stress in the pathogenesis of nonalcoholic fatty liver disease. Free Radic Biol Med 152:116–141. https://doi.org/10.1016/j.freeradbiomed.2020.02.025. (PMID: 10.1016/j.freeradbiomed.2020.02.02532156524)
Zhao TJ, Wu W, Sui LH et al (2022) Reactive oxygen species-based nanomaterials for the treatment of myocardial ischemia reperfusion injuries. Bioact Mater 7:47–72. https://doi.org/10.1016/j.bioactmat.2021.06.006. (PMID: 10.1016/j.bioactmat.2021.06.00634466716)
Chen S, Saeed A, Liu Q et al (2023) Macrophages in immunoregulation and therapeutics. Signal Transduct Target Ther 8(1):207. https://doi.org/10.1038/s41392-023-01452-1. (PMID: 10.1038/s41392-023-01452-13721155910200802)
Khol M, Ma F, Lei L et al (2024) A Frontier Review of Nutraceutical Chinese Yam. Foods 13(10). https://doi.org/10.3390/foods13101426.
Chen PY, Tu YX, Wu CT et al (2004) Continuous hot pressurized solvent extraction of 1,1-diphenyl-2-picrylhydrazyl free radical scavenging compounds from Taiwan yams (Dioscorea alata). J Agric Food Chem 52(7):1945–1949. https://doi.org/10.1021/jf0351826. (PMID: 10.1021/jf035182615053534)
Yu ST, Han B, Bai XY et al (2020) 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. J Ethnopharmacol 263:113223. https://doi.org/10.1016/j.jep.2020.113223. (PMID: 10.1016/j.jep.2020.11322332791294)
Amat N, Amat R, Abdureyim S et al (2014) Aqueous extract of dioscorea opposita thunb. normalizes the hypertension in 2K1C hypertensive rats. BMC Complement Altern Med 14(1):36. https://doi.org/10.1186/1472-6882-14-36. (PMID: 10.1186/1472-6882-14-36244477763904168)
Zou J, Xu MJ, Wen LR et al (2020) Structure and physicochemical properties of native starch and resistant starch in Chinese yam (Dioscorea opposita Thunb). Carbohydr Polym 237:116188. https://doi.org/10.1016/j.carbpol.2020.116188. (PMID: 10.1016/j.carbpol.2020.11618832241403)
Shao YL, Mao LC, Guan WL et al (2020) Physicochemical and structural properties of low-amylose Chinese yam (Dioscorea opposita Thunb.) starches. Int J Biol Macromol 164:427–433. https://doi.org/10.1016/j.ijbiomac.2020.07.054.
Zhang CX, Ding J, Bian ZY et al (2024) Multi-level fingerprinting and immune activity evaluation for polysaccharides from Dioscorea opposita Thunb. Int J Biol Macromol 280(Pt 1135767. https://doi.org/10.1016/j.ijbiomac.2024.
Ma FY, Zhang Y, Wen YR et al (2017) Emulsification properties of polysaccharides from Dioscorea opposita Thunb. Food Chem 221:919–925. https://doi.org/10.1016/j.foodchem.2016.11.073. (PMID: 10.1016/j.foodchem.2016.11.07327979295)
Oh PS, Lim KT (2009) Glycoprotein isolated from Dioscorea batatas Decne modulates expressions of IL-4 and IL-10 in primary-cultured mouse lymphocytes. Cell Biochem Funct 27(5):316–322. https://doi.org/10.1002/cbf.1577. (PMID: 10.1002/cbf.157719548268)
Oh P-S, Lim K-T (2007) Antioxidant activity of Dioscorea batatas Decne glycoprotein. Eur Food Res Technol 226(3):507–515. https://doi.org/10.1007/s00217-007-0563-6. (PMID: 10.1007/s00217-007-0563-6)
Lee SJ, Lim KT (2008) Inhibitory effect of 30-kDa phytoglycoprotein on expression of TNF-alpha and COX-2 via activation of PKCalpha and ERK 1/2 in LPS-stimulated RAW 264.7 cells. Mol Cell Biochem 317(1–2):151–159. https://doi.org/10.1007/s11010-008-9843-0. (PMID: 10.1007/s11010-008-9843-018566751)
Li WY, Shi J, Wu XP et al (2025) Regulatory effects of yam (Dioscorea opposita Thunb.) glycoprotein on energy metabolism in C2C12 and 3T3-L1 cells and on crosstalk between these two cells. J Ethnopharmacol 338(Pt 1):119013. https://doi.org/10.1016/j.jep.2024.119013. (PMID: 10.1016/j.jep.2024.11901339481620)
Niu XF, He ZH, Li WF et al (2017) Immunomodulatory Activity of the Glycoprotein Isolated from the Chinese Yam (Dioscorea opposita Thunb). Phytother Res 31(10):1557–1563. https://doi.org/10.1002/ptr.5896. (PMID: 10.1002/ptr.589628840617)
Niu XF, Zang LL, Li WQ et al (2020) Anti-inflammatory effect of Yam Glycoprotein on lipopolysaccharide-induced acute lung injury via the NLRP3 and NF-kappaB/TLR4 signaling pathway. Int Immunopharmacol 81:106024. https://doi.org/10.1016/j.intimp.2019.106024. (PMID: 10.1016/j.intimp.2019.10602431784404)
Pang L, Liao Q, Zou L et al (2022) Two glycoproteins from medicinal insect Periplaneta americana (L.) promote diabetic wound healing via macrophage polarization modulation. Int J Biol Macromol 209:2130–2141. https://doi.org/10.1016/j.ijbiomac.2022.04.193. (PMID: 10.1016/j.ijbiomac.2022.04.19335500775)
Zhang M, Ou X, Shi H et al (2023) Isolation, structures and biological activities of medicinal glycoproteins from natural resources: A review. International Journal of Biological Macromolecules 244:125406.ijbiomac. 2023.125406 https://doi.org/10.1016/jijbiomac.2023.125406.
Dalal D, Singh L, Singh A (2023) Desmethylglycitein Attenuates Scopolamine-Induced Cognitive Deficits via Nrf-2 Activation and IL-1β Suppression. Neurophysiology 55(5):161–170. https://doi.org/10.1007/s11062-025-09967-9. (PMID: 10.1007/s11062-025-09967-9)
Singh A, Singh L, Dalal D (2025) Neuroprotective potential of hispidulin and diosmin: a review of molecular mechanisms. Metab Brain Dis 40(5):188. https://doi.org/10.1007/s11011-025-01615-9. (PMID: 10.1007/s11011-025-01615-940257619)
Yousaf A, Singh A, Dalal D (2026) Fisetin as a neuroprotective agent: Docking-based modulation of dopaminergic and inflammatory pathways in Parkinson’s disease. Neurophysiology https://doi.org/10.1007/s11062-025-09981-x .
Weindel CG, Martinez EL, Zhao X et al (2022) Mitochondrial ROS promotes susceptibility to infection via gasdermin D-mediated necroptosis. Cell 185(17):3214–3231e3223. https://doi.org/10.1016/j.cell.2022.06.038. (PMID: 10.1016/j.cell.2022.06.038359074049531054)
Sies H, Jones DP (2020) Reactive oxygen species (ROS) as pleiotropic physiological signalling agents. Nat Rev Mol Cell Biol 21(7):363–383. https://doi.org/10.1038/s41580-020-0230-3. (PMID: 10.1038/s41580-020-0230-332231263)
Mailloux RJ (2020) Protein S-glutathionylation reactions as a global inhibitor of cell metabolism for the desensitization of hydrogen peroxide signals. Redox Biol 32:101472. https://doi.org/10.1016/j.redox.2020.101472. (PMID: 10.1016/j.redox.2020.101472321717267076094)
Okoye CN, Koren SA, Wojtovich AP (2023) Mitochondrial complex I ROS production and redox signaling in hypoxia. Redox Biol 67:102926. https://doi.org/10.1016/j.redox.2023.102926. (PMID: 10.1016/j.redox.2023.1029263787153310598411)
Li MZ, Wen JJ, Huang XJ et al (2022) Interaction between polysaccharides and toll-like receptor 4: Primary structural role, immune balance perspective, and 3D interaction model hypothesis. Food Chem 374:131586. https://doi.org/10.1016/j.foodchem.2021.131586. (PMID: 10.1016/j.foodchem.2021.13158634839969)
Li M, Huang X, Wen J et al (2023) Innate immune receptors co-recognition of polysaccharides initiates multi-pathway synergistic immune response. Carbohydr Polym 305:120533. https://doi.org/10.1016/j.carbpol.2022.120533. (PMID: 10.1016/j.carbpol.2022.12053336737186)
Wicherska-Pawłowska K, Wróbel T, Rybka J (2021) Toll-Like Receptors (TLRs), NOD-Like Receptors (NLRs), and RIG-I-Like Receptors (RLRs) in Innate Immunity. TLRs, NLRs, and RLRs Ligands as Immunotherapeutic Agents for Hematopoietic Diseases. Int J Mol Sci 22(24). https://doi.org/10.3390/ijms222413397.
Li DY, Wu MH (2021) Pattern recognition receptors in health and diseases. Signal Transduct Tar 6(1):291. https://doi.org/10.1038/s41392-021-00687-0. (PMID: 10.1038/s41392-021-00687-0)
Vaure C, Liu Y (2014) A comparative review of toll-like receptor 4 expression and functionality in different animal species. Front Immunol 5:316. https://doi.org/10.3389/fimmu.2014.00316. (PMID: 10.3389/fimmu.2014.00316250717774090903)
Ren AQ, Wang HJ, Zhu HY et al (2021) Glycoproteins From Rabdosia japonica var. glaucocalyx Regulate Macrophage Polarization and Alleviate Lipopolysaccharide-Induced Acute Lung Injury in Mice via TLR4/NF-kappaB Pathway. Front Pharmacol 12:693298. https://doi.org/10.3389/fphar.2021.693298. (PMID: 10.3389/fphar.2021.693298343668498333617)
Yu Q, Nie SP, Wang JQ et al (2014) Toll-like receptor 4-mediated ROS signaling pathway involved in Ganoderma atrum polysaccharide-induced tumor necrosis factor-alpha secretion during macrophage activation. Food Chem Toxicol 66:14–22. https://doi.org/10.1016/j.fct.2014.01.018. (PMID: 10.1016/j.fct.2014.01.01824447977)
Hasegawa T, Matsuguchi T, Noda K et al (2002) Toll-like receptor 2 is at least partly involved in the antitumor activity of glycoprotein from Chlorella vulgaris. Int Immunopharmacol 2(4):579–589. https://doi.org/10.1016/s1567-5769(02)00002-4. (PMID: 10.1016/s1567-5769(02)00002-411962736)
Wang HY, Ge JC, Zhang FY et al (2022) Dendrobium officinale polysaccharide promotes M1 polarization of TAMs to inhibit tumor growth by targeting TLR2. Carbohydr Polym 292:119683. https://doi.org/10.1016/j.carbpol.2022.119683. (PMID: 10.1016/j.carbpol.2022.11968335725176)
Ren WK, Ban JF, Xia YY et al (2023) Echinacea purpurea-derived homogeneous polysaccharide exerts anti-tumor efficacy via facilitating M1 macrophage polarization. Innov (Camb) 4(2):100391. https://doi.org/10.1016/j.xinn.2023.100391. (PMID: 10.1016/j.xinn.2023.100391)
Li MG, Yang YH, Xiong LT et al (2023) Metabolism, metabolites, and macrophages in cancer. J Hematol Oncol 16(1):80. https://doi.org/10.1186/s13045-023-01478-6. (PMID: 10.1186/s13045-023-01478-63749127910367370)
Contributed Indexing: Keywords: Immunomodulation; Macrophages; NF-κB signaling pathway; TLR4; Yam glycoprotein
Substance Nomenclature: 0 (Toll-Like Receptor 4)
0 (Glycoproteins)
0 (Reactive Oxygen Species)
0 (NF-kappa B)
0 (Tlr4 protein, mouse)
0 (Immunologic Factors)
0 (Plant Proteins)
0 (Toll-Like Receptor Agonists)
Entry Date(s): Date Created: 20260618 Date Completed: 20260618 Latest Revision: 20260618
Update Code: 20260618
DOI: 10.1007/s11033-026-12114-0
PMID: 42313284
Βάση Δεδομένων: MEDLINE