{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:46:07Z","timestamp":1785415567101,"version":"3.56.0"},"reference-count":37,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:00:00Z","timestamp":1775174400000},"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":"publisher","award":["NRF-2019R1C1C1003558"],"award-info":[{"award-number":["NRF-2019R1C1C1003558"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2024-00350385"],"award-info":[{"award-number":["RS-2024-00350385"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2022-NR070873"],"award-info":[{"award-number":["RS-2022-NR070873"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2022-NR072339"],"award-info":[{"award-number":["RS-2022-NR072339"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"award":["NRF-2019R1C1C1003558"],"award-info":[{"award-number":["NRF-2019R1C1C1003558"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]},{"award":["RS-2024-00350385"],"award-info":[{"award-number":["RS-2024-00350385"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]},{"award":["RS-2022-NR070873"],"award-info":[{"award-number":["RS-2022-NR070873"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]},{"award":["RS-2022-NR072339"],"award-info":[{"award-number":["RS-2022-NR072339"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Vascular inflammation and impaired endothelial regeneration contribute to chronic degenerative disorders, including ocular neovascularization and retinal degeneration. Nutritional bioactives that modulate molecular pathways governing angiogenesis and tissue remodeling represent promising adjunct strategies for vascular health. This study investigated whether cocoa powder (CP) regulates hypoxia-driven molecular signaling and attenuates vascular inflammation and degeneration. Methods: The vascular-modulatory effects of CP were examined in human umbilical vein endothelial cells (HUVECs) and in murine models of alkali-induced corneal neovascularization and N-methyl-N-nitrosourea (MNU)-induced retinal degeneration. Hypoxia-inducible factor-1\u03b1 (HIF-1\u03b1) signaling and downstream angiogenic targets were assessed by Western blotting and quantitative PCR. Endothelial migration, tube formation, and transwell assays were performed to evaluate angiogenic responses. In vivo, oral CP (50 or 200 mg\/kg) was administered, and vascular growth, inflammatory and remodeling markers, and retinal structural integrity were analyzed by histology, immunofluorescence, and protein expression. Results: At non-cytotoxic concentrations (0.1\u20131.0 \u03bcg\/mL), CP suppressed hypoxia-induced HIF-1\u03b1 protein stabilization without altering HIF-1\u03b1 mRNA levels and reduced expression of VEGFA, EPO, and GLUT1. CP significantly inhibited VEGF-A-induced endothelial migration, network formation, and chemotactic invasion. In alkali-injured corneas, CP reduced the neovascularized area and downregulated VEGF, MMP2, MMP9, \u03b1-smooth muscle actin, and Ninj1, indicating attenuation of vascular inflammation and fibrotic remodeling. In the MNU model, CP preserved outer nuclear layer thickness, reduced glial activation (GFAP), maintained rhodopsin expression, and decreased MMP9 induction. Conclusions: CP functions as a nutritional modulator of hypoxia-responsive and inflammatory pathways, suppressing pathological angiogenesis while supporting structural preservation in degenerative vascular conditions. These findings highlight the translational potential of dietary polyphenol-rich interventions in regulating vascular inflammation and regeneration.<\/jats:p>","DOI":"10.3390\/nu18071150","type":"journal-article","created":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T00:19:32Z","timestamp":1775434772000},"page":"1150","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cocoa Powder Modulates HIF-1\u03b1 Stability and Inhibits Ocular Angiogenic and Degenerative Pathology"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7629-287X","authenticated-orcid":false,"given":"Su Jung","family":"Hwang","sequence":"first","affiliation":[{"name":"School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0669-7674","authenticated-orcid":false,"given":"InWha","family":"Park","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeo Jin","family":"Sa","sequence":"additional","affiliation":[{"name":"Nexpharm Korea Co., Ltd., Cheongju-si 16841, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyu Ha","family":"Lee","sequence":"additional","affiliation":[{"name":"Nexpharm Korea Co., Ltd., Cheongju-si 16841, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9961-4093","authenticated-orcid":false,"given":"Chung Sub","family":"Kim","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea"},{"name":"Department of Biopharmaceutical Convergence, Sungkyunkwan University, Suwon 16419, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4826-7954","authenticated-orcid":false,"given":"Hyo-Jong","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1097\/ICU.0000000000001049","article-title":"Current trends in the management of corneal neovascularization","volume":"35","author":"Rangu","year":"2024","journal-title":"Curr. 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