{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:45:19Z","timestamp":1791942319383,"version":"4.3.4"},"reference-count":100,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T00:00:00Z","timestamp":1754265600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Unilever (Colworth, UK) and Innovate UK","award":["101129"],"award-info":[{"award-number":["101129"]}]},{"name":"Unilever (Colworth, UK) and Innovate UK","award":["QB14"],"award-info":[{"award-number":["QB14"]}]},{"name":"Qatar Foundation","award":["101129"],"award-info":[{"award-number":["101129"]}]},{"name":"Qatar Foundation","award":["QB14"],"award-info":[{"award-number":["QB14"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>A dietary supplement, trans-resveratrol and hesperetin (tRES+HESP)\u2014also known as GlucoRegulate\u2014induces increased expression of glyoxalase 1 (Glo1) by activation of transcription factor Nrf2, countering accumulation of the reactive dicarbonyl glycating agent, methylglyoxal. tRES+HESP corrected insulin resistance and decreased fasting and postprandial plasma glucose and low-grade inflammation in overweight and obese subjects in a clinical trial. The aim of this study was to explore, for the first time, health-beneficial gene expression other than Glo1 induced by tRES+HESP in human endothelial cells and fibroblasts in primary culture and HepG2 hepatoma cell line and activity of cis-resveratrol (cRES) as a Glo1 inducer. We measured antioxidant response element-linked gene expression in these cells in response to 5 \u00b5M tRES+HESP by the NanoString method. tRES+HESP increases gene expression linked to the prevention of dicarbonyl stress, lipid peroxidation, oxidative stress, proteotoxicity and hyperglycemia-linked glycolytic overload. Downstream benefits were improved regulation of glucose and lipid metabolism and decreased inflammation, extracellular matrix remodeling and senescence markers. The median effective concentration of tRES was ninefold lower than cRES in the Glo1 inducer luciferase reporter assay. The GlucoRegulate supplement provides a new treatment option for the prevention of type 2 diabetes and metabolic dysfunction\u2013associated steatotic liver disease and supports healthy aging.<\/jats:p>","DOI":"10.3390\/antiox14080956","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T10:58:26Z","timestamp":1754564306000},"page":"956","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Glyoxalase 1 Inducer, trans-Resveratrol and Hesperetin\u2013Dietary Supplement with Multi-Modal Health Benefits"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9184-2980","authenticated-orcid":false,"given":"Mingzhan","family":"Xue","sequence":"first","affiliation":[{"name":"Diabetes Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation, Doha P.O. Box 34110, Qatar"},{"name":"Clinical Sciences Research Laboratories, Warwick Medical School, University Hospital, University of Warwick, Clifford Bridge Road, Coventry CV2 2DX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naila","family":"Rabbani","sequence":"additional","affiliation":[{"name":"Clinical Sciences Research Laboratories, Warwick Medical School, University Hospital, University of Warwick, Clifford Bridge Road, Coventry CV2 2DX, UK"},{"name":"Glovitality Ltd., 167\u2013169 Great Portland Street, London W1W 5PF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7659-443X","authenticated-orcid":false,"given":"Paul J.","family":"Thornalley","sequence":"additional","affiliation":[{"name":"Diabetes Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation, Doha P.O. Box 34110, Qatar"},{"name":"Clinical Sciences Research Laboratories, Warwick Medical School, University Hospital, University of Warwick, Clifford Bridge Road, Coventry CV2 2DX, UK"},{"name":"Glovitality Ltd., 167\u2013169 Great Portland Street, London W1W 5PF, UK"},{"name":"College of Health and Life Sciences, Hamad Bin Khalifa University, Qatar Foundation, Doha P.O. Box 34110, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2282","DOI":"10.2337\/db16-0153","article-title":"Improved glycemic control and vascular function in overweight and obese subjects by glyoxalase 1 inducer formulation","volume":"65","author":"Xue","year":"2016","journal-title":"Diabetes"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1677","DOI":"10.1042\/CS20160025","article-title":"Methylglyoxal-induced dicarbonyl stress in aging and disease: First steps towards glyoxalase 1-based treatments","volume":"130","author":"Rabbani","year":"2016","journal-title":"Clin. Sci."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Irshad, Z., Xue, M., Ashour, A., Larkin, J.R., Thornalley, P.J., and Rabbani, N. (2019). 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