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It is characterized by chronic inflammation and angiogenesis. Palm oil-derived tocotrienol-rich fraction (TRF), a substance with anti-inflammatory and anti-angiogenic properties, may provide protection against DR development. Therefore, in this study, we investigated the effect of TRF on retinal vascular and morphological changes\u00a0in diabetic rats. The effects of TRF on the retinal expression of inflammatory and angiogenic markers were also studied in the streptozotocin (STZ)-induced diabetic rats.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Male <jats:italic>Sprague Dawley<\/jats:italic> rats weighing 200\u2013250\u00a0g were grouped into normal rats (N) and diabetic rats. Diabetes was induced by intraperitoneal injection of streptozotocin (55\u00a0mg\/kg body weight) whereas N similarly received citrate buffer. STZ-injected rats with blood glucose of more than 20 mmol\/L were considered diabetic and were divided into vehicle-treated (DV) and TRF-treated (DT) groups. N and DV received vehicle, whereas DT received TRF (100\u00a0mg\/kg body weight) via oral gavage once daily for 12 weeks. Fundus images were captured at week 0 (baseline), week 6 and week 12 post-STZ induction to estimate vascular diameters. At the end of experimental period, rats were euthanized, and retinal tissues were collected for morphometric analysis and measurement of NF\u03baB, phospho-NF\u03baB (Ser536), HIF-1\u03b1 using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA). Retinal inflammatory and angiogenic cytokines expression were measured by ELISA and real-time quantitative PCR.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>TRF preserved the retinal layer thickness (GCL, IPL, INL and OR; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) and retinal venous diameter (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). TRF also lowered the retinal NF\u03baB activation (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) as well as expressions of IL-1\u03b2, IL-6, TNF-\u03b1, IFN-\u03b3, iNOS and MCP-1 (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) compared to vehicle-treated diabetic rats. Moreover, TRF also reduced retinal expression of VEGF (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), IGF-1 (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) and HIF-1\u03b1 (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) compared to vehicle-treated rats with diabetes.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Oral TRF provided protection against retinal inflammation and angiogenesis in rats with STZ-induced diabetes by suppressing the expression of the markers of retinal inflammation and angiogenesis.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12906-023-04005-9","type":"journal-article","created":{"date-parts":[[2023,6,2]],"date-time":"2023-06-02T07:28:17Z","timestamp":1685690897000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Tocotrienol-rich fraction reduces retinal inflammation and angiogenesis in rats with streptozotocin-induced diabetes"],"prefix":"10.1186","volume":"23","author":[{"given":"Muhammad Zulfiqah","family":"Sadikan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurul Alimah","family":"Abdul Nasir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nor Salmah","family":"Bakar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Igor","family":"Iezhitsa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renu","family":"Agarwal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,6,2]]},"reference":[{"key":"4005_CR1","doi-asserted-by":"crossref","unstructured":"Teo ZL, Tham Y-C, Yu MCY, Chee ML, Rim TH, Cheung N et al. 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