{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T03:49:36Z","timestamp":1761709776732,"version":"3.41.2"},"reference-count":33,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,10,5]],"date-time":"2020-10-05T00:00:00Z","timestamp":1601856000000},"content-version":"vor","delay-in-days":278,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"APTORUM"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Evidence-Based Complementary and Alternative Medicine"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:p><jats:italic>Purpose<\/jats:italic>. Retinal ischemia is a medical condition associated with numerous retinal vascular disorders, such as age\u2010related macular degeneration, glaucoma, and diabetic retinopathy. This in vitro cell and in vivo animal study investigated not only the protective effect of S\u2010allyl L\u2010cysteine (SAC, an active component of garlic) against retinal ischemia but also its associated protective mechanisms. <jats:italic>Methods<\/jats:italic>. Retinal ischemia was mimicked by raising the intraocular pressure to 120\u2009mmHg for 1 hour in one eye. The effects of pre\u2010\/postischemic administration of vehicle vs. SAC 0.18\u2009mg vs. SAC 0.018\u2009mg vs. SAC 0.0018\u2009mg treatments on retina cells were evaluated through cellular viability (MTT assay), flash electroretinograms (ERGs), and fluorogold retrograde labelling (retinal ganglion cell (RGC) counting). Also, protein immunoblot was utilized to assess the role of Wnt, hypoxia inducible factor (HIF)\u20101<jats:italic>\u03b1<\/jats:italic>, and vascular endothelium factor (VEGF) in the proposed anti\u2010ischemic mechanism. Lastly, the safety of drug consumption was investigated for changes in the animal\u2019s body weight, ERG waves, and blood biochemical parameters (e.g., glucose levels). <jats:italic>Results<\/jats:italic>. The characteristic ischemic changes including significant reduction in ERG b\u2010wave ratio and RGC number were significantly counteracted by pre\u2010 and postischemic low dose of SAC. Additionally, ischemia\u2010induced overexpression of Wnt\/HIF\u20101<jats:italic>\u03b1<\/jats:italic>\/VEGF protein was ameliorated significantly by preischemic low dose of SAC. In terms of the animal safety, no significant body weight and electrophysiological differences were observed among defined different concentrations of SAC without following ischemia. In low SAC dosage and vehicle groups, various blood biochemical parameters were normal; however, high and medium concentrations of SAC significantly lowered the levels of uric acid, Hb, and MCHC. <jats:italic>Conclusion<\/jats:italic>. This study shows that preischemic administration of low SAC dosage has been proved to be safe and most effective against rat retinal ischemia electrophysiologically and\/or histopathologically. Moreover, counteracting the ischemia\u2010induced overexpression of Wnt\/HIF\u20101<jats:italic>\u03b1<\/jats:italic>\/VEGF might presently explain SAC\u2019s anti\u2010ischemic mechanism.<\/jats:p>","DOI":"10.1155\/2020\/3025946","type":"journal-article","created":{"date-parts":[[2020,10,8]],"date-time":"2020-10-08T12:27:24Z","timestamp":1602160044000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Fortified S\u2010Allyl L\u2010Cysteine: Animal Safety, Effect on Retinal Ischemia, and Role of Wnt in the Underlying Therapeutic Mechanism"],"prefix":"10.1155","volume":"2020","author":[{"given":"Windsor Wen-Jin","family":"Chao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Kuang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Howard Wen-Haur","family":"Chao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wynn Hwai-Tzong","family":"Pan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1545-9936","authenticated-orcid":false,"given":"Hsiao-Ming","family":"Chao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,10,5]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_10_1_2","DOI":"10.1186\/s13020-016-0109-6"},{"doi-asserted-by":"publisher","key":"e_1_2_10_2_2","DOI":"10.2337\/diacare.21.1.143"},{"doi-asserted-by":"publisher","key":"e_1_2_10_3_2","DOI":"10.1089\/ars.2012.4583"},{"doi-asserted-by":"publisher","key":"e_1_2_10_4_2","DOI":"10.1016\/s0092-8674(04)00216-8"},{"doi-asserted-by":"publisher","key":"e_1_2_10_5_2","DOI":"10.1002\/humu.21250"},{"doi-asserted-by":"publisher","key":"e_1_2_10_6_2","DOI":"10.1093\/hmg\/ddw041"},{"doi-asserted-by":"publisher","key":"e_1_2_10_7_2","DOI":"10.1142\/s0192415x14500451"},{"doi-asserted-by":"publisher","key":"e_1_2_10_8_2","DOI":"10.1089\/jop.2011.0099"},{"doi-asserted-by":"publisher","key":"e_1_2_10_9_2","DOI":"10.1038\/onc.2016.304"},{"doi-asserted-by":"publisher","key":"e_1_2_10_10_2","DOI":"10.1128\/mcb.23.1.359-369.2003"},{"doi-asserted-by":"publisher","key":"e_1_2_10_11_2","DOI":"10.1038\/srep16151"},{"key":"e_1_2_10_12_2","first-page":"886","article-title":"Tissue factor induces VEGF expression via activation of the Wnt\/\u03b2-catenin signaling pathway in ARPE-19 cells","volume":"22","author":"Wang Y.","year":"2016","journal-title":"Molecular Vision"},{"doi-asserted-by":"publisher","key":"e_1_2_10_13_2","DOI":"10.1186\/s12906-018-2256-z"},{"doi-asserted-by":"publisher","key":"e_1_2_10_14_2","DOI":"10.2337\/db13-1309"},{"doi-asserted-by":"publisher","key":"e_1_2_10_15_2","DOI":"10.1016\/s0891-5849(01)00460-9"},{"key":"e_1_2_10_16_2","first-page":"2120","article-title":"S-allyl cysteine protects retinal pigment epithelium cells from hydroquinone-induced apoptosis through mitigating cellular response to oxidative stress","volume":"24","author":"Sun Z. 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