{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T21:20:29Z","timestamp":1787606429891,"version":"build-2736575974"},"reference-count":46,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T00:00:00Z","timestamp":1779840000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82104887"],"award-info":[{"award-number":["82104887"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873314"],"award-info":[{"award-number":["81873314"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82374517"],"award-info":[{"award-number":["82374517"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2022A1515220131"],"award-info":[{"award-number":["2022A1515220131"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Food Science &amp; Nutrition"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Osteoarthritis (OA), a representative chronic degenerative joint disease, is closely associated with chronic inflammation and dysregulated cell survival. Dietary polyphenols are recognized for their protective roles against chronic inflammatory conditions. Duhuo Jisheng Decoction (DHJST), a polyphenol\u2010rich traditional herbal formula, is widely used for degenerative joint diseases. This study aims to explore the novel mechanisms of DHJST\u2010derived bioactives in enhancing the chondroprotective potential of mesenchymal stem cell\u2010derived exosomes. We integrated network pharmacology and machine learning to identify the core AKT\u2010related targets of DHJST. Bone marrow mesenchymal stem cells (BMSCs) were preconditioned with DHJST\u2010containing serum to generate enhanced exosomes (DHJST\u2010Exos), applying to IL\u20101\u03b2\u2013stimulated rat chondrocytes and a collagenase\u2010induced OA rat model. The therapeutic efficacy was evaluated via inflammatory markers, extracellular matrix (ECM) homeostasis, and apoptosis assays, with the PI3K\/AKT inhibitor Rigosertib used for mechanistic validation. Network pharmacology identified key bioactive polyphenols including wogonin, quercetin, kaempferol, and other polyphenol\u2010like constituents in DHJST that significantly modulate the PI3K\/AKT pathway. DHJST \u2010Exos effectively suppressed TNF\u2010\u03b1 and IL\u20106, reduced MMP\u201013 and ADAMTS\u20105 levels, and restored COL2A1 and Aggrecan expression. Furthermore, DHJST \u2010Exos attenuated chondrocyte apoptosis by regulating the Caspase\u20103\/Bax\/Bcl\u20102 axis. Mechanistically, DHJST \u2010Exos up\u2010regulated the expression of hub genes JUN and KDR via AKT phosphorylation, a protective effect that was significantly abrogated by Rigosertib. This study demonstrates that polyphenol\u2010rich DHJST enhances the therapeutic efficacy of BMSC\u2010derived exosomes against OA by activating the AKT signaling pathway and its key nodes, JUN and KDR. This synergistic strategy, combining dietary bioactives with exosome\u2010mediated delivery, represents a promising adjunctive approach for the management of chronic degenerative joint diseases.<\/jats:p>","DOI":"10.1002\/fsn3.71867","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T05:38:58Z","timestamp":1779946738000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Polyphenol\u2010Rich Duhuo Jisheng Decoction Enhances Mesenchymal Stem Cell\u2013Derived Exosome\u2013Mediated Chondroprotection via PI3K\/AKT Signaling in Osteoarthritis"],"prefix":"10.1002","volume":"14","author":[{"given":"Zhouwei","family":"Liao","sequence":"first","affiliation":[{"name":"Orthopaedics Department Shenzhen Traditional Chinese Medicine Hospital  Shenzhen Guangdong China"},{"name":"The Forth Clinical College of Guangzhou University of Chinese Medicine  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiran","family":"Wang","sequence":"additional","affiliation":[{"name":"The Forth Clinical College of Guangzhou University of Chinese Medicine  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunwan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Orthopaedics Department Shenzhen Traditional Chinese Medicine Hospital  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixin","family":"Wang","sequence":"additional","affiliation":[{"name":"Orthopaedics Department Shenzhen Traditional Chinese Medicine Hospital  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian","family":"Yu","sequence":"additional","affiliation":[{"name":"Orthopaedics Department Shenzhen Traditional Chinese Medicine Hospital  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinqiang","family":"Ni","sequence":"additional","affiliation":[{"name":"Orthopaedics Department Shenzhen Traditional Chinese Medicine Hospital  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaoqun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Orthopaedics Department Shenzhen Traditional Chinese Medicine Hospital  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangdong Second Traditional Chinese Medicine Hospital (Guangdong Province Engineering Technology Research Institute of Traditional Chinese Medicine)  Guangzhou Guangdong China"},{"name":"The Research Team on Bone and Joint Degeneration and Injury Guangdong Provincial Academy of Chinese Medical Sciences  Guangzhou Guangdong China"},{"name":"The Fifth Clinical College of Guangzhou University of Chinese Medicine  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junzheng","family":"Yang","sequence":"additional","affiliation":[{"name":"The Fifth Clinical College of Guangzhou University of Chinese Medicine  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5471-2035","authenticated-orcid":false,"given":"Hui","family":"Xie","sequence":"additional","affiliation":[{"name":"Orthopaedics Department Shenzhen Traditional Chinese Medicine Hospital  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,27]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcna.2019.10.007"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/7813921"},{"key":"e_1_2_13_4_1","first-page":"32","article-title":"The Potential Role of Medicinal Plants in Bone Regeneration","volume":"25","author":"Barbalho S. 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