{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:28:41Z","timestamp":1785421721722,"version":"3.56.0"},"reference-count":64,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Ministry of Education, Korea","doi-asserted-by":"publisher","award":["F25YY8109033"],"award-info":[{"award-number":["F25YY8109033"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"Ministry of Education, Korea","doi-asserted-by":"publisher","award":["F26YY8109033"],"award-info":[{"award-number":["F26YY8109033"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"award":["F25YY8109033"],"award-info":[{"award-number":["F25YY8109033"]}],"id":[{"id":"https:\/\/ror.org\/01p262204","id-type":"ROR","asserted-by":"publisher"}]},{"award":["F26YY8109033"],"award-info":[{"award-number":["F26YY8109033"]}],"id":[{"id":"https:\/\/ror.org\/01p262204","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CIMB"],"abstract":"<jats:p>Although oxidative stress plays a critical role in age-related macular degeneration (AMD) progression, natural product\u2013derived single compounds against AMD remain largely unexplored. We investigated the protective effects and underlying mechanism of \u03b1-iso-cubebene against AMD-like retinal injury. Alterations in key phenotypes for AMD were analyzed in AMD-mimicking models using ARPE-19 cells co-treated with blue light (BL) and N-retinylidene-N-retinylethanolamine (A2E), as well as BL-exposed BALB\/c mice. In BL+A2E-treated ARPE-19 cells, \u03b1-iso-cubebene reduced intracellular reactive oxygen species (ROS) and nitric oxide (NO) production and restored superoxide dismutase (SOD) activity and nuclear factor erythroid 2\u2013related factor 2 (Nrf2), suggesting enhancement of the antioxidant defense system. Furthermore, \u03b1-iso-cubebene improved cell viability, reduced apoptotic cell populations, and regulated apoptosis-related signaling pathways under oxidative stress conditions. It also attenuated cyclooxygenase-2 (COX-2)-mediated inducible nitric oxide synthase (iNOS) signaling and was associated with reduced inflammasome-related signaling. Importantly, these protective effects were consistently observed regarding the protection of histopathological structure and normalization of inflammatory cytokines in the retina of BL-exposed BALB\/c mice. Collectively, our results demonstrate that \u03b1-iso-cubebene, as a potential therapeutic candidate, alleviates AMD-like retinal injury and was associated with enhanced antioxidant responses and reduced inflammatory and apoptotic signaling markers.<\/jats:p>","DOI":"10.3390\/cimb48070669","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T02:11:57Z","timestamp":1782785517000},"page":"669","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["\u03b1-Iso-Cubebene Alleviates AMD-like Retinal Injury Through Modulation of Oxidative Stress and Inflammatory Response"],"prefix":"10.3390","volume":"48","author":[{"given":"Ye Ryeong","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Biomaterials Science (BK21 FOUR Program), Laboratory Animals Resources Center, College of Natural Resources and Life Science, Pusan National University, Miryang 50463, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayun","family":"Seol","sequence":"additional","affiliation":[{"name":"Department of Biomaterials Science (BK21 FOUR Program), Laboratory Animals Resources Center, College of Natural Resources and Life Science, Pusan National University, Miryang 50463, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su Jin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biomaterials Science (BK21 FOUR Program), Laboratory Animals Resources Center, College of Natural Resources and Life Science, Pusan National University, Miryang 50463, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Eun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomaterials Science (BK21 FOUR Program), Laboratory Animals Resources Center, College of Natural Resources and Life Science, Pusan National University, Miryang 50463, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee Jin","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Biomaterials Science (BK21 FOUR Program), Laboratory Animals Resources Center, College of Natural Resources and Life Science, Pusan National University, Miryang 50463, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su Jeong","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Biomaterials Science (BK21 FOUR Program), Laboratory Animals Resources Center, College of Natural Resources and Life Science, Pusan National University, Miryang 50463, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su Ha","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biomaterials Science (BK21 FOUR Program), Laboratory Animals Resources Center, College of Natural Resources and Life Science, Pusan National University, Miryang 50463, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye Eun","family":"Ryu","sequence":"additional","affiliation":[{"name":"Department of Biomaterials Science (BK21 FOUR Program), Laboratory Animals Resources Center, College of Natural Resources and Life Science, Pusan National University, Miryang 50463, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Whan","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Horticultural Bioscience, Pusan National University, Miryang 50463, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6617-5004","authenticated-orcid":false,"given":"Sun Il","family":"Choi","sequence":"additional","affiliation":[{"name":"Research Institute, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang 10408, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5144-1725","authenticated-orcid":false,"given":"Dae Youn","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Biomaterials Science (BK21 FOUR Program), Laboratory Animals Resources Center, College of Natural Resources and Life Science, Pusan National University, Miryang 50463, Republic of Korea"},{"name":"Longevity & Wellbeing Research Center, Life and Industry Convergence Research Institute, Pusan National University, Miryang 50463, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/s41572-021-00265-2","article-title":"Age-related macular degeneration","volume":"7","author":"Fleckenstein","year":"2021","journal-title":"Nat. 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