{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T11:20:47Z","timestamp":1789125647688,"version":"build-2803163510"},"reference-count":53,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Morchella polysaccharides are commonly labeled as antioxidants because they quench radicals in chemical assays, yet this designation does not establish biological redox efficacy. This critical narrative review reframes these fungal polymers as candidate redox-modulating biomacromolecules. A structured search of PubMed and OpenAlex through 17 August 2026 yielded 84 unique records after deduplication; 31 core Morchella-polysaccharide reports with redox-relevant experimental evidence were mapped, supplemented by five mechanistically adjacent studies. Evidence was graded from chemical assays (E1) to human intervention (E5), with a separate causality score (M0\u2013M2). Structure-resolved studies indicate that molecular weight, branching, charge, conformation, source, and acetylation or degradation can modify activity, but process-related co-variation and incomplete purity controls preclude universal structure\u2013activity rules. Cellular and animal studies repeatedly implicate PI3K\/Akt\u2013Nrf2\/HO-1, AMPK\/Sirt1, mitochondrial apoptosis, NF-\u03baB\/NLRP3, and gut-mediated pathways, although most reported links remain associative. Within the databases and search strategy used, no eligible human intervention study was identified. We propose a translational roadmap requiring identity-controlled materials, orthogonal redox endpoints, causal pathway perturbation, exposure and microbiota studies, and standardized early-phase trials. The field should move beyond DPPH-positive claims toward reproducible mechanisms and biologically credible redox protection.<\/jats:p>","DOI":"10.3390\/nu18182981","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T10:51:37Z","timestamp":1789123897000},"page":"2981","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Morchella\u00a0Polysaccharides\u00a0in\u00a0Oxidative Stress\u2014Structure\u2013Activity Relationships, Redox Signaling, and Translational Evidence"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0369-0513","authenticated-orcid":false,"given":"Na","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Translational Genomics, Faculty of Health, Medicine & Life Sciences, GROW Institute for Oncology and Reproduction, Maastricht University, 6200 MD Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6867-4034","authenticated-orcid":false,"given":"Yi","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.redox.2015.01.002","article-title":"Oxidative stress: A concept in redox biology and medicine","volume":"4","author":"Sies","year":"2015","journal-title":"Redox Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/s41580-020-0230-3","article-title":"Reactive oxygen species (ROS) as pleiotropic physiological signalling agents","volume":"21","author":"Sies","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1089\/ars.2006.8.1865","article-title":"Redefining Oxidative Stress","volume":"8","author":"Jones","year":"2006","journal-title":"Antioxid. Redox Signal."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/nri3423","article-title":"Beyond oxidative stress: An immunologist\u2019s guide to reactive oxygen species","volume":"13","author":"Nathan","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1038\/ni.1831","article-title":"Thioredoxin-interacting protein links oxidative stress to inflammasome activation","volume":"11","author":"Zhou","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4290","DOI":"10.1021\/jf0502698","article-title":"Standardized Methods for the Determination of Antioxidant Capacity and Phenolics in Foods and Dietary Supplements","volume":"53","author":"Prior","year":"2005","journal-title":"J. Agric. Food Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.freeradbiomed.2011.09.030","article-title":"Measuring reactive oxygen and nitrogen species with fluorescent probes: Challenges and limitations","volume":"52","author":"Kalyanaraman","year":"2012","journal-title":"Free Radic. Biol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"360438","DOI":"10.1155\/2014\/360438","article-title":"Lipid Peroxidation: Production, Metabolism, and Signaling Mechanisms of Malondialdehyde and 4-Hydroxy-2-Nonenal","volume":"2014","author":"Ayala","year":"2014","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/j.ijbiomac.2018.08.148","article-title":"Polysaccharide FMP-1 from Morchella esculenta attenuates cellular oxidative damage in human alveolar epithelial A549 cells through PI3K\/AKT\/Nrf2\/HO-1 pathway","volume":"120","author":"Li","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"139886","DOI":"10.1016\/j.ijbiomac.2025.139886","article-title":"A polysaccharide from Morchella esculenta mycelia: Structural characterization and protective effect on antioxidant stress on PC12 cells against H2O2-induced oxidative damage","volume":"298","author":"Chen","year":"2025","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"140444","DOI":"10.1016\/j.ijbiomac.2025.140444","article-title":"Hepatoprotective effects of polysaccharide from Morchella esculenta are associated with activation of the AMPK\/Sirt1 signaling pathway in mice with NAFLD","volume":"301","author":"Wang","year":"2025","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e71483","DOI":"10.1002\/fsn3.71483","article-title":"Hepatoprotective Effect of Morchella Mycelia Polysaccharides on Alcoholic Liver Injury and Its Mechanism Involving the Modulation of NOD-Like Receptor Signaling Pathway","volume":"14","author":"Hu","year":"2026","journal-title":"Food Sci. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"130656","DOI":"10.1016\/j.ijbiomac.2024.130656","article-title":"Extraction, structure and antioxidant activity of the polysaccharides from morels (Morchella spp.): A review","volume":"264","author":"Tian","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1007\/s00253-011-3711-7","article-title":"Effects of polysaccharides from Morchella conica on nitric oxide production in lipopolysaccharide-treated macrophages","volume":"94","author":"Huang","year":"2012","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1176","DOI":"10.1038\/s41401-025-01725-1","article-title":"Morchella polysaccharide ameliorates myocardial infarction inflammation in mice through increasing gut microbiota-derived 12-HEPE","volume":"47","author":"Su","year":"2026","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1016\/j.carbpol.2009.09.032","article-title":"Optimization for the production of exopolysaccharides from Morchella esculenta SO-02 in submerged culture and its antioxidant activities in vitro","volume":"79","author":"Meng","year":"2010","journal-title":"Carbohydr. Polym."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4564","DOI":"10.1016\/j.biortech.2010.01.113","article-title":"Extraction optimization and in vivo antioxidant activities of exopolysaccharide by Morchella esculenta SO-01","volume":"101","author":"Meng","year":"2010","journal-title":"Bioresour. Technol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1007\/s00449-012-0720-6","article-title":"Production, characterization and antioxidant activity of exopolysaccharides from submerged culture of Morchella crassipes","volume":"35","author":"He","year":"2012","journal-title":"Bioprocess Biosyst. Eng."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1016\/j.ijbiomac.2018.09.134","article-title":"Antioxidant, anti-hyperlipidemia and hepatic protection of enzyme-assisted Morchella esculenta polysaccharide","volume":"120","author":"Dong","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Pan, X., Xu, L., Meng, J., Chang, M., Cheng, Y., Geng, X., Guo, D., and Liu, R. (2022). Ultrasound-Assisted Deep Eutectic Solvents Extraction of Polysaccharides From Morchella importuna: Optimization, Physicochemical Properties, and Bioactivities. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.912014"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e16024","DOI":"10.1111\/jfpp.16024","article-title":"Influences of subcritical water extraction on the characterization and biological properties of polysaccharides from Morchella sextelata","volume":"46","author":"Li","year":"2022","journal-title":"J. Food Process. Preserv."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Li, X., Sun, Q., Li, S., Chen, W., Shi, Z., Xu, Z., Xu, L., Chen, M., and Li, Z. (2024). Production with Fermentation Culture and Antioxidant Activity of Polysaccharides from Morchella esculenta. Fermentation, 10.","DOI":"10.3390\/fermentation10010046"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.carbpol.2018.04.069","article-title":"Structural characterization, in vitro and in vivo antioxidant activities of a heteropolysaccharide from the fruiting bodies of Morchella esculenta","volume":"195","author":"Cai","year":"2018","journal-title":"Carbohydr. Polym."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"151128","DOI":"10.1016\/j.ijbiomac.2026.151128","article-title":"PANoptosis inhibition by Morchella sextelata polysaccharide mediates neuroprotection in Alzheimer\u2019s disease models","volume":"351","author":"Wang","year":"2026","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Li, F., Jin, Y., Wang, J., and Xu, H. (2022). Structure Identification of Two Polysaccharides from Morchella sextelata with Antioxidant Activity. Foods, 11.","DOI":"10.3390\/foods11070982"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1111\/1750-3841.14470","article-title":"Antioxidant and Antiproliferative Activities of Modified Polysaccharides Originally Isolated from Morchella Angusticepes Peck","volume":"84","author":"Tang","year":"2019","journal-title":"J. Food Sci."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"BSR20194522","DOI":"10.1042\/BSR20194522","article-title":"Effect of \u03b3-irradiation on the structure and antioxidant activity of polysaccharide isolated from the fruiting bodies of Morchella sextelata","volume":"40","author":"Xiong","year":"2020","journal-title":"Biosci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"108669","DOI":"10.1016\/j.bioorg.2025.108669","article-title":"Antioxidant and immunomodulatory effects of acetylated Morchella esculenta polysaccharide in DSS-induced ulcerative colitis mice","volume":"163","author":"Ma","year":"2025","journal-title":"Bioorganic Chem."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Xu, N., Lu, Y., Hou, J., Liu, C., and Sun, Y. (2018). A Polysaccharide Purified from Morchella conica Pers. Prevents Oxidative Stress Induced by H2O2 in Human Embryonic Kidney (HEK) 293T Cells. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19124027"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"120453","DOI":"10.1016\/j.carbpol.2022.120453","article-title":"Structure and hepatoprotective activity of Usp10\/NF-\u03baB\/Nrf2 pathway-related Morchella esculenta polysaccharide","volume":"303","author":"Teng","year":"2023","journal-title":"Carbohydr. Polym."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1016\/j.biopha.2016.07.016","article-title":"Neuroprotective effect of crude polysaccharide isolated from the fruiting bodies of Morchella importuna against H2O2-induced PC12 cell cytotoxicity by reducing oxidative stress","volume":"83","author":"Xiong","year":"2016","journal-title":"Biomed. Pharmacother."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6262","DOI":"10.1002\/fsn3.2586","article-title":"NMCP-2 polysaccharide purified from Morchella conica effectively prevents doxorubicin-induced cardiotoxicity by decreasing cardiomyocyte apoptosis and myocardial oxidative stress","volume":"9","author":"Xu","year":"2021","journal-title":"Food Sci. Nutr."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Gao, Q., Wang, L., Yang, M., Ren, X., and Kong, Q. (2026). Investigation of Polysaccharides from Morchella esculenta Cap and Stipe: Structural Characterization and Antioxidant Activities in a Caenorhabditis elegans Model. ACS Food Sci. Technol.","DOI":"10.1021\/acsfoodscitech.6c00406"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1039\/c3fo60033e","article-title":"Evaluation of the antioxidant activity of extracellular polysaccharides from Morchella esculenta","volume":"4","author":"Fu","year":"2013","journal-title":"Food Funct."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Xu, Y., Xie, L., Tang, J., He, X., Zhang, Z., Chen, Y., Zhou, J., Gan, B., and Peng, W. (2021). Morchella importuna Polysaccharides Alleviate Carbon Tetrachloride-Induced Hepatic Oxidative Injury in Mice. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.669331"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Qiu, R., Zhang, Z., Almutairi, M.H., Nawaz, S., and Dong, S. (2024). Effect of Morchella esculenta polysaccharides on the rectal microbiota of mice challenged with lipopolysaccharides. Front. Vet. Sci., 11.","DOI":"10.3389\/fvets.2024.1446924"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/s41538-026-00763-1","article-title":"Mechanism of Morchella polysaccharide in anti-fatigue: The role of the gut microbiota-metabolite axis in mice","volume":"10","author":"Liu","year":"2026","journal-title":"npj Sci. Food"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/35092620","article-title":"A new receptor for \u03b2-glucans","volume":"413","author":"Brown","year":"2001","journal-title":"Nature"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/nature10071","article-title":"Activation of the innate immune receptor Dectin-1 upon formation of a \u2018phagocytic synapse\u2019","volume":"472","author":"Goodridge","year":"2011","journal-title":"Nature"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1152\/physrev.00023.2017","article-title":"The KEAP1-NRF2 System: A Thiol-Based Sensor-Effector Apparatus for Maintaining Redox Homeostasis","volume":"98","author":"Yamamoto","year":"2018","journal-title":"Physiol. Rev."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e00099\u201320","DOI":"10.1128\/MCB.00099-20","article-title":"The Molecular Mechanisms Regulating the KEAP1-NRF2 Pathway","volume":"40","author":"Baird","year":"2020","journal-title":"Mol. Cell. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1038\/nrm2952","article-title":"Mitochondria and cell death: Outer membrane permeabilization and beyond","volume":"11","author":"Tait","year":"2010","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.procbio.2024.05.023","article-title":"Preparation, structural characterization and protective effect on PC12 cells of polysaccharides from the stipe of Morchella esculenta","volume":"144","author":"Cheng","year":"2024","journal-title":"Process Biochem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1038\/nature07813","article-title":"AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity","volume":"458","author":"Feige","year":"2009","journal-title":"Nature"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"904","DOI":"10.1016\/j.ijbiomac.2019.02.088","article-title":"Anti-inflammatory effects of Morchella esculenta polysaccharide and its derivatives in fine particulate matter-treated NR8383 cells","volume":"129","author":"Li","year":"2019","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.chom.2018.05.012","article-title":"The Impact of Dietary Fiber on Gut Microbiota in Host Health and Disease","volume":"23","author":"Makki","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Rehman, A.U., Siddiqui, N.Z., Farooqui, N.A., Alam, G., Gul, A., Ahmad, B., Asim, M., Khan, A.I., Xin, Y., and Zexu, W. (2022). Morchella esculenta mushroom polysaccharide attenuates diabetes and modulates intestinal permeability and gut microbiota in a type 2 diabetic mice model. Front. Nutr., 9.","DOI":"10.3389\/fnut.2022.984695"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"149343","DOI":"10.1016\/j.foodchem.2026.149343","article-title":"Enzyme-hydrolyzed polysaccharides from Morchella importuna: Preparation, structural characterization, and multi-omics of lipid metabolism regulation","volume":"517","author":"Li","year":"2026","journal-title":"Food Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1007\/s10719-022-10058-8","article-title":"Structural characterization and biological activities of a new polysaccharide isolated from Morchella sextelata","volume":"39","author":"Zhang","year":"2022","journal-title":"Glycoconj. J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"27683","DOI":"10.1007\/s13399-022-03357-5","article-title":"A new acidic polysaccharide and its sulfated derivative from cultured Morchella sextelata fruiting bodies and their antioxidant and immunoregulatory activities","volume":"14","author":"Wen","year":"2024","journal-title":"Biomass Convers. Biorefinery"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1934578X261429628","DOI":"10.1177\/1934578X261429628","article-title":"Morchella esculenta Polysaccharide Alleviates Lipopolysaccharide-Induced Experimental Hepatitis in Mice","volume":"21","author":"Chen","year":"2026","journal-title":"Nat. Product. Commun."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e70058","DOI":"10.1002\/efd2.70058","article-title":"Structural Characterization of Morchella esculenta Polysaccharides and Its Ability to Modulate Intestinal Barrier and Intestinal Microbiota in Dextran Sulfate Sodium-Induced Colitis Mice","volume":"6","author":"Chen","year":"2025","journal-title":"eFood"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Percie du Sert, N., Hurst, V., Ahluwalia, A., Alam, S., Avey, M.T., Baker, M., Browne, W.J., Clark, A., Cuthill, I.C., and Dirnagl, U. (2020). The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. PLoS Biol., 18.","DOI":"10.1371\/journal.pbio.3000410"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/18\/2981\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T11:01:43Z","timestamp":1789124503000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/18\/2981"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,11]]},"references-count":53,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["nu18182981"],"URL":"https:\/\/doi.org\/10.3390\/nu18182981","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,11]]}}}