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In this study, two fractions of fermented Dendrobium officinale polysaccharides (FDOPs) were successfully isolated through a multi-stage purification strategy including gradient ethanol precipitation, gel column chromatography, and ion exchange chromatography with Lactobacillus reuteri CCFM863. Structural characterization revealed that both Dendrobium officinale polysaccharide fractions consisted of (1\u21924)-\u03b2-D-Manp, (1\u21924)-\u03b2-D-Glcp, and (1\u21924)-\u03b1-D-Glcp residues. The anti-inflammatory efficacy and keratinocyte-protective potential of FDOPs (FDOP-1A and FDOP-2A) were investigated by using lipopolysaccharide (LPS)-induced RAW264.7 and HaCaT cells models, which showed significant inhibitions on the inflammatory factors of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-\u03b1), nitric oxide (NO), and interleukin-1 beta (IL-1\u03b2); recovered levels of filaggrin (FLG), aquaporin 3 (AQP3), transient receptor potential vanilloid 4 (TRPV4), cathelicidin antimicrobial peptide (CAMP)\/LL-37, and adiponectin (ADIPOQ); and the reduced protein expression of the TLR4\/I\u03baB-\u03b1\/NF-\u03baB\/NLRP3 pathway. Notably, the FDOPs exhibited a remarkable reactive oxygen species (ROS) scavenging capacity, demonstrating superior antioxidant activity. Therefore, FDOPs show dual anti-inflammatory and antioxidant properties, making them suitable as active ingredients for modulating epidermal inflammation and promoting skin barrier repair.<\/jats:p>","DOI":"10.3390\/molecules30132875","type":"journal-article","created":{"date-parts":[[2025,7,7]],"date-time":"2025-07-07T04:43:37Z","timestamp":1751863417000},"page":"2875","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Bioactive Polysaccharides from Fermented Dendrobium officinale: Structural Insights and Their Role in Skin Barrier Repair"],"prefix":"10.3390","volume":"30","author":[{"given":"Wanshuai","family":"Wang","sequence":"first","affiliation":[{"name":"Shandong Key Laboratory of Glycoscience and Glycotherapeutics, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China"},{"name":"Key Laboratory of Marine Drugs of Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anqi","family":"Zou","sequence":"additional","affiliation":[{"name":"Shandong Key Laboratory of Glycoscience and Glycotherapeutics, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China"},{"name":"Key Laboratory of Marine Drugs of Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingtao","family":"Yu","sequence":"additional","affiliation":[{"name":"Infinitus (China) Company Ltd., Guangzhou 510405, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Wang","sequence":"additional","affiliation":[{"name":"Shandong Key Laboratory of Glycoscience and Glycotherapeutics, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China"},{"name":"Key Laboratory of Marine Drugs of Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daotong","family":"Tan","sequence":"additional","affiliation":[{"name":"Shandong Key Laboratory of Glycoscience and Glycotherapeutics, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China"},{"name":"Key Laboratory of Marine Drugs of Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaiye","family":"Yang","sequence":"additional","affiliation":[{"name":"Infinitus (China) Company Ltd., Guangzhou 510405, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4377-3989","authenticated-orcid":false,"given":"Chao","family":"Cai","sequence":"additional","affiliation":[{"name":"Shandong Key Laboratory of Glycoscience and Glycotherapeutics, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China"},{"name":"Key Laboratory of Marine Drugs of Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China"},{"name":"Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6372-9750","authenticated-orcid":false,"given":"Guangli","family":"Yu","sequence":"additional","affiliation":[{"name":"Shandong Key Laboratory of Glycoscience and Glycotherapeutics, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China"},{"name":"Key Laboratory of Marine Drugs of Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China"},{"name":"Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1126\/science.abo0693","article-title":"Microbiota and maintenance of skin barrier function","volume":"376","author":"Grice","year":"2022","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Yang, S., and Alalaiwe, A. 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