{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T05:18:22Z","timestamp":1787980702919,"version":"build-2784847793"},"reference-count":37,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T00:00:00Z","timestamp":1787356800000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ift.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Food Science"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      Intestinal mucosal homeostasis is fundamentally governed by the T\u2010helper 1\/T\u2010helper 2 (Th1\/Th2) cytokine equilibrium within immune induction sites such as Peyer's patches (PPs). While cashew nuts (\n                      <jats:italic>Anacardium occidentale<\/jats:italic>\n                      L.) are globally consumed for their nutritional value, the immunomodulatory potential of their polar constituents remains under\u2010characterized. In this study, an activity\u2010guided fractionation strategy led to the isolation of nine phenolic compounds. Their effects on T\u2010helper polarization were evaluated ex vivo using murine PP cells following oral administration. We identified a structural \u201cmolecular switch\u201d that dictates the direction of immune modulation: dihydroflavonols, specifically aromadendrin (1) and naringenin (2), significantly upregulated Th1 cytokines, interferon\u2010gamma (IFN\u2010\u03b3), and interleukin\u20102 (IL\u20102), whereas flavan\u20103\u2010ols, such as afzelechin (3) and epiafzelechin (4), promoted a Th2\u2010biased response, interleukin\u20104 (IL\u20104). Structure\u2013activity relationship (SAR) analysis revealed that the C\u2010ring oxidation state (C4\u2010carbonyl group) is the primary determinant of the immunomodulatory direction, while the C2\u2013C3 stereochemical configuration specifically modulates the inhibitory potency against Th1\u2010type cytokines. Integrated network pharmacology and molecular docking simulations further mapped these divergent activities to distinct molecular targets: the Th1\u2010promoting effects of aromadendrin were associated with the SRC\/phosphoinositide 3\u2010kinase (PI3K)\u2013protein kinase B (Akt) axis, while the Th2\u2010bias of afzelechin was linked to the epidermal growth factor receptor (EGFR)\/mitogen\u2010activated protein kinase (MAPK) signaling cascade. These findings provide a structural and mechanistic framework for utilizing specific cashew\u2010derived flavonoids as targeted functional ingredients to calibrate Th1\/Th2 imbalances in intestinal immune disorders.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/1750-3841.71395","type":"journal-article","created":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T10:16:03Z","timestamp":1787393763000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cashew\u2010Derived Flavonoids Modulate the Th1\/Th2 Balance at Peyer's Patches via a C\u2010Ring Oxidation\u2013Dependent Molecular Switch"],"prefix":"10.1111","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-2659-2968","authenticated-orcid":false,"given":"Yuan","family":"Wu","sequence":"first","affiliation":[{"name":"College of Jiyang Zhejiang A&amp;F University  Zhuji China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinhan","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Jiyang Zhejiang A&amp;F University  Zhuji China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Yan","sequence":"additional","affiliation":[{"name":"College of Jiyang Zhejiang A&amp;F University  Zhuji China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianyu","family":"Shen","sequence":"additional","affiliation":[{"name":"College of Jiyang Zhejiang A&amp;F University  Zhuji China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiyun","family":"Jin","sequence":"additional","affiliation":[{"name":"Zhejiang Chinese Medical University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maorong","family":"Suo","sequence":"additional","affiliation":[{"name":"College of Jiyang Zhejiang A&amp;F University  Zhuji China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,22]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2022.e11066"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaw7479"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1079\/pns2001118"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2009.01.033"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2025.157096"},{"issue":"2","key":"e_1_2_12_7_1","first-page":"121","article-title":"Studies on the Active Constituents in Vine Stem of Spatholobus suberectus","volume":"30","author":"Cui Y. 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