{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T12:54:02Z","timestamp":1791982442156,"version":"4.4.0"},"reference-count":39,"publisher":"American Chemical Society (ACS)","issue":"40","license":[{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T00:00:00Z","timestamp":1790899200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100005046","name":"Heilongjiang Provincial Science and Technology Department","doi-asserted-by":"publisher","award":["LH2022C039"],"award-info":[{"award-number":["LH2022C039"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013061","name":"Department of Science and Technology of Jilin Province","doi-asserted-by":"publisher","award":["20240601087RC"],"award-info":[{"award-number":["20240601087RC"]}],"id":[{"id":"10.13039\/501100013061","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Zearalenone (ZEA) is a prevalent mycotoxin inducing hepatotoxic effects. Hyperoside (HYP), a flavonoid derived from Actinidia arguta bee pollen, exhibits hepatoprotective properties against ZEA; however, the molecular mechanisms underlying this protection remain incompletely characterized. This study integrated in vivo piglet models, in vitro porcine hepatocytes, network pharmacology, and molecular docking to characterize the molecular targets of HYP. The results demonstrated that HYP significantly attenuated ZEA-induced hepatic lesions and oxidative stress. Computational analyses pinpointed the PI3K\/AKT signaling pathway as the core target of HYP. In vitro validation revealed that HYP phenocopied the AKT activator SC79 in suppressing ZEA-induced hepatocyte apoptosis, an efficacy partially abrogated by the PI3K inhibitor LY294002. Conclusively, HYP ameliorates ZEA-induced hepatotoxicity by activating the PI3K\/AKT axis to mitigate oxidative stress and apoptosis, underscoring its translational potential as a functional detoxifying additive for food and feed applications.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c05739","type":"journal-article","created":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T18:01:49Z","timestamp":1790964109000},"page":"31810-31823","source":"Crossref","is-referenced-by-count":0,"title":["Hyperoside Derived\nfrom\n                    <i>Actinidia arguta<\/i>\n                    Bee Pollen Alleviates\nZearalenone-Induced Hepatotoxicity and Oxidative\nStress in Piglets via the PI3K\/AKT Signaling Pathway"],"prefix":"10.1021","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6738-2810","authenticated-orcid":true,"given":"Nannan","family":"Liu","sequence":"first","affiliation":[{"name":"Jilin Agricultural Science and Technology College , ,","place":["Jilin, China, 132101"]},{"name":"College of Food Science and Nutritional Engineering , ,","place":["Jilin, China, 132101"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0505-8808","authenticated-orcid":true,"given":"Dongfei","family":"You","sequence":"additional","affiliation":[{"name":"Northeast Agricultural University , , ,","place":["Harbin, China, 150030"]},{"name":"Heilongjiang Provincial Key Laboratory of Pathogenic Mechanism for Animal Disease and Comparative Medicine , ,","place":["Harbin, China, 150030"]},{"name":"Northeast Agricultural University , , ,","place":["Harbin, China, 150030"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0378-5779","authenticated-orcid":true,"given":"Yunfei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Jilin Agricultural Science and Technology College , ,","place":["Jilin, China, 132101"]},{"name":"College of Food Science and Nutritional Engineering , ,","place":["Jilin, China, 132101"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6454-2789","authenticated-orcid":true,"given":"Tianyu","family":"Han","sequence":"additional","affiliation":[{"name":"Northeast Agricultural University , , ,","place":["Harbin, China, 150030"]},{"name":"Heilongjiang Provincial Key Laboratory of Pathogenic Mechanism for Animal Disease and Comparative Medicine , ,","place":["Harbin, China, 150030"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8583-3711","authenticated-orcid":true,"given":"Guangliang","family":"Shi","sequence":"additional","affiliation":[{"name":"Northeast Agricultural University , , ,","place":["Harbin, China, 150030"]},{"name":"Heilongjiang Provincial Key Laboratory of Pathogenic Mechanism for Animal Disease and Comparative Medicine , ,","place":["Harbin, China, 150030"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,10,2]]},"reference":[{"key":"2026101408092904600_cit1","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.tifs.2020.02.001","article-title":"Composition and functionality of bee pollen: A review","volume":"98","author":"Thakur","year":"2020","journal-title":"Trends Food Sci. 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Int."},{"key":"2026101408092904600_cit4","doi-asserted-by":"publisher","first-page":"3009","DOI":"10.3390\/molecules27093009","article-title":"Hyperoside:\nA review of its structure, synthesis, pharmacology, pharmacokinetics\nand toxicity","volume":"27","author":"Xu","year":"2022","journal-title":"Molecules"},{"key":"2026101408092904600_cit5","doi-asserted-by":"publisher","first-page":"4503","DOI":"10.2147\/JIR.S418222","article-title":"Potential\nimplications of hyperoside on oxidative stress-induced human diseases:\nA comprehensive review","volume":"16","author":"Wang","year":"2023","journal-title":"J. Inflamm. Res."},{"key":"2026101408092904600_cit6","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.3389\/fphar.2020.01065","article-title":"Hyperoside\nprotected against oxidative\nstress-induced liver injury via the PHLPP2-AKT-GSK-3\u03b2 signaling\npathway in vivo and in vitro","volume":"11","author":"Xing","year":"2020","journal-title":"Front. 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Food Biochem."},{"key":"2026101408092904600_cit29","doi-asserted-by":"publisher","first-page":"635","DOI":"10.12688\/f1000research.122341.1","article-title":"Hyperoside:\nA review of pharmacological effects","volume":"11","author":"Li","year":"2022","journal-title":"F1000research"},{"key":"2026101408092904600_cit30","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1002\/pca.3093","article-title":"Development\nof new and validated HPTLC methods for\nthe qualitative and quantitative analysis of hyperforin, hypericin\nand hyperoside contents in Hypericum species","volume":"33","author":"Sac\u0327\u0131c\u0131","year":"2022","journal-title":"Phytochem. Anal."},{"key":"2026101408092904600_cit31","doi-asserted-by":"publisher","first-page":"199","DOI":"10.3390\/toxins13030199","article-title":"Zearalenone induces\napoptosis and cytoprotective autophagy in chicken granulosa cells\nby PI3K-AKT-mTOR and MAPK signaling pathways","volume":"13","author":"Zhu","year":"2021","journal-title":"Toxins"},{"key":"2026101408092904600_cit32","doi-asserted-by":"publisher","first-page":"217","DOI":"10.3390\/ijms22010217","article-title":"Kaempferol inhibits\nzearalenone-induced oxidative stress and apoptosis via the PI3K\/Akt-mediated\nNrf2 signaling pathway: In vitro and in vivo studies","volume":"22","author":"Rajendran","year":"2020","journal-title":"IJMS"},{"key":"2026101408092904600_cit33","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1042\/bj3510095","article-title":"Specificity\nand mechanism\nof action of some commonly used protein kinase inhibitors","volume":"351","author":"Davies","year":"2000","journal-title":"Biochem. 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Rec."}],"container-title":["Journal of Agricultural\nand Food Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jafc.6c05739","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/40\/31810\/68737721\/acs.jafc.6c05739.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jafcau\/article-pdf\/74\/40\/31810\/68737721\/acs.jafc.6c05739.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T12:29:07Z","timestamp":1791980947000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jafcau\/article\/74\/40\/31810\/5444087\/Hyperoside-Derived-from-Actinidia-arguta-Bee"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,2]]},"references-count":39,"journal-issue":{"issue":"40","published-online":{"date-parts":[[2026,10,2]]},"published-print":{"date-parts":[[2026,10,14]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jafc.6c05739","relation":{},"ISSN":["0021-8561","1520-5118"],"issn-type":[{"value":"0021-8561","type":"print"},{"value":"1520-5118","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,2]]}}}