{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:43:25Z","timestamp":1790685805279,"version":"4.1.0"},"reference-count":52,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,28]],"date-time":"2021-12-28T00:00:00Z","timestamp":1640649600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010731","name":"Faculty of Medicine, Chiang Mai University","doi-asserted-by":"publisher","award":["110-2564"],"award-info":[{"award-number":["110-2564"]}],"id":[{"id":"10.13039\/501100010731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Psoriasis is a complex inflammatory disease characterized by hyperproliferative keratinocyte caused by active PI3K\/AKT signaling. TNF-\u03b1 concentrated in the psoriatic lesions stimulates AKT activation. We previously discovered that oxyresveratrol inhibited inflammation via suppressing AKT phosphorylation, therefore oxyresveratrol may possess a conserved property to block AKT activation and proliferation in keratinocyte in response to TNF-\u03b1. Our current study proved that oxyresveratrol exhibited potent anti-proliferative effects against TNF-\u03b1. These effects are explained by the findings that oxyresveratrol could potentially inhibit TNF-\u03b1-stimulated AKT and GSK3-\u03b2 activation in a dose-dependent manner, and its inhibitory pattern was comparable to that of a specific PI3K inhibitor. Results from immunofluorescence supported that oxyresveratrol effectively inhibited AKT and GSK3-\u03b2 activation in individual cells upon TNF-\u03b1 stimulation. Furthermore, functional assay confirmed that oxyresveratrol repressed the expansion of the HaCaT colony over 3 days, and this was caused by the ability of oxyresveratrol to induce cell cycle arrest at S and G2\/M phases and the reduction in the expression of a proliferative marker (Ki-67) and a survival marker (MCL-1). Given the importance of TNF-\u03b1 and the PI3K\/AKT pathway in the psoriatic phenotype, we anticipate that oxyresveratrol, which targets the TNF-\u03b1-stimulated PI3K\/AKT pathway, would represent a promising psoriasis therapy in the near future.<\/jats:p>","DOI":"10.3390\/pharmaceutics14010063","type":"journal-article","created":{"date-parts":[[2021,12,28]],"date-time":"2021-12-28T06:55:03Z","timestamp":1640674503000},"page":"63","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Oxyresveratrol Inhibits TNF-\u03b1-Stimulated Cell Proliferation in Human Immortalized Keratinocytes (HaCaT) by Suppressing AKT Activation"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0708-0328","authenticated-orcid":false,"given":"Nitwara","family":"Wikan","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3777-0848","authenticated-orcid":false,"given":"Phateep","family":"Hankittichai","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phatarawat","family":"Thaklaewphan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8951-8532","authenticated-orcid":false,"given":"Saranyapin","family":"Potikanond","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Research Center for Development of Local Lanna Rice and Rice Products, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4794-8539","authenticated-orcid":false,"given":"Wutigri","family":"Nimlamool","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Research Center for Development of Local Lanna Rice and Rice Products, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1046\/j.1365-2230.2001.00832.x","article-title":"Psoriasis-epidemiology and clinical spectrum","volume":"26","author":"Christophers","year":"2001","journal-title":"Clin. 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