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In this study, three extraction methods (hot water, acid, and alkaline) for chestnut polysaccharides were compared in terms of yield and immunomodulatory activity. Two homogeneous polysaccharides, CP-1a and CP-1b, were purified and characterized. Structural analysis revealed that CP-1a possesses a novel backbone of \u21924)-\u03b2-D-Galp-(1\u2192 and \u21924)-\u03b1-D-Glcp-(1\u2192 residues with O-6 branches. In vitro assays with RAW 264.7 cells showed that CP-1a significantly enhanced proliferation, phagocytosis, and M1 polarization by promoting cytokine secretion and activating the TLR4\/NF-\u03baB pathway. In vivo, CP-1a restored splenic immune cell proportions and enhanced peritoneal macrophage function in immunosuppressed mice. These findings identify CP-1a as an immunostimulatory chestnut polysaccharide and support its potential for functional foods or therapeutic applications.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c04232","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T01:02:04Z","timestamp":1790038924000},"page":"30735-30755","source":"Crossref","is-referenced-by-count":0,"title":["Structural Characterization\nand Immunomodulatory Activity\nof Acid-Extracted Polysaccharides from Chestnut (\n                    <i>Castanea Mollissima<\/i>\n                    Blume)"],"prefix":"10.1021","volume":"74","author":[{"given":"Fan","family":"Wei","sequence":"first","affiliation":[{"name":"Nankai University , , ,","place":["Tianjin, PR China, 300071"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenting","family":"Yu","sequence":"additional","affiliation":[{"name":"Nankai University , , ,","place":["Tianjin, PR China, 300071"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoxin","family":"Cui","sequence":"additional","affiliation":[{"name":"Nankai University , , ,","place":["Tianjin, PR China, 300071"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ang","family":"Li","sequence":"additional","affiliation":[{"name":"Nankai University , , ,","place":["Tianjin, PR China, 300071"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Wang","sequence":"additional","affiliation":[{"name":"Nankai University , , ,","place":["Tianjin, PR China, 300071"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Lv","sequence":"additional","affiliation":[{"name":"Nankai University , , ,","place":["Tianjin, PR China, 300071"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuemeng","family":"Ji","sequence":"additional","affiliation":[{"name":"Nankai University , , ,","place":["Tianjin, PR China, 300071"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6228-9220","authenticated-orcid":true,"given":"Yaozhong","family":"Hu","sequence":"additional","affiliation":[{"name":"Nankai University , , ,","place":["Tianjin, PR China, 300071"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bowei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Nankai University , , ,","place":["Tianjin, PR China, 300071"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7990-7515","authenticated-orcid":true,"given":"Shuo","family":"Wang","sequence":"additional","affiliation":[{"name":"Nankai University , , ,","place":["Tianjin, PR China, 300071"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"issue":"1","key":"2026100711070390800_cit1","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1159\/000533602","article-title":"Mitochondrial Damage-Associated\nMolecular Patterns and Metabolism in the Regulation of Innate Immunity","volume":"15","author":"Lyu","year":"2023","journal-title":"J. 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Gastroenterol.\nHepatol."},{"key":"2026100711070390800_cit5","doi-asserted-by":"publisher","first-page":"5297539","DOI":"10.1155\/2018\/5297539","article-title":"Antioxidant\nActivities\nand Repair Effects on Oxidatively Damaged HK-2 Cells of Tea Polysaccharides\nwith Different Molecular Weights","volume":"2018","author":"Sun","year":"2018","journal-title":"Oxid. Med.\nCell. Longevity"},{"issue":"47","key":"2026100711070390800_cit6","doi-asserted-by":"publisher","first-page":"30357","DOI":"10.1021\/acs.jafc.5c11565","article-title":"Structural\nCharacterization and Gastrointestinal Fate of a High-Molecular-Weight\nHericium erinaceus Polysaccharide during Digestion and Fermentation","volume":"73","author":"Fu","year":"2025","journal-title":"J. Agric. 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