{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T18:53:13Z","timestamp":1789152793436,"version":"build-2803163510"},"reference-count":80,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2023,7,18]],"date-time":"2023-07-18T00:00:00Z","timestamp":1689638400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Hyperhomocysteinemia (HHcy) worsens cardiovascular outcomes by impairing vascular function and promoting chronic inflammation via release of danger-associated molecular patterns, such as high-mobility group box-1 (HMGB-1). Elevated levels of HMGB-1 have recently been reported in patients with HHcy. Therefore, targeting HMGB-1 may be a potential therapy to improve HHcy-induced cardiovascular pathologies. This study aimed to further elucidate HMGB-1\u2032s role during acute HHcy and HHcy-induced atherogenesis and to determine if inhibiting HMGB-1 with glycyrrhizic acid (Glyz) improved vascular function. Male New Zealand White rabbits (n = 25) were placed on either a standard control chow (CD; n = 15) or atherogenic diet (AD; n = 10) for 4 weeks. Rabbit serum and Krebs taken from organ bath studies were collected to quantify HMGB-1 levels. Isometric tension analysis was performed on abdominal aorta (AA) rings from CD and AD rabbits. Rings were incubated with homocysteine (Hcy) [3 mM] for 60 min to induce acute HHcy or rhHMGB-1 [100 nM]. Vascular function was assessed by relaxation to cumulative doses of acetylcholine. Markers of vascular dysfunction and inflammation were quantified in the endothelium, media, and adventitia of AA rings. HMGB-1 was significantly upregulated in serum (p &lt; 0.0001) and Krebs (p &lt; 0.0001) after Hcy exposure or an AD. Incubation with Hcy (p &lt; 0.0001) or rhHMGB-1 (p &lt; 0.0001) and an AD (p &lt; 0.0001) significantly reduced relaxation to acetylcholine, which was markedly improved by Glyz. HMGB-1 expression was elevated (p &lt; 0.0001) after Hcy exposure and AD (p &lt; 0.0001) and was normalized after Glyz treatment. Moreover, markers of vascular function, cell stress and inflammation were also reduced after Glyz. These results demonstrate that HMGB-1 has a central role during HHcy-induced vascular dysfunction and inhibiting it with Glyz could be a potential treatment option for cardiovascular diseases.<\/jats:p>","DOI":"10.3390\/nu15143186","type":"journal-article","created":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T00:54:01Z","timestamp":1689728041000},"page":"3186","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Glycyrrhizic Acid Inhibits High-Mobility Group Box-1 and Homocysteine-Induced Vascular Dysfunction"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4801-8061","authenticated-orcid":false,"given":"Laura Kate","family":"Gadanec","sequence":"first","affiliation":[{"name":"Institute of Health and Sport, Victoria University, Melbourne, VIC 3030, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0316-3860","authenticated-orcid":false,"given":"Ulf","family":"Andersson","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health, Karolinska Institute, 17177 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6788-2771","authenticated-orcid":false,"given":"Vasso","family":"Apostolopoulos","sequence":"additional","affiliation":[{"name":"Institute of Health and Sport, Victoria University, Melbourne, VIC 3030, Australia"},{"name":"Immunology Program, Australian Institute for Musculoskeletal Science, Melbourne, VIC 3021, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Zulli","sequence":"additional","affiliation":[{"name":"Institute of Health and Sport, Victoria University, Melbourne, VIC 3030, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.2147\/IPRP.S133088","article-title":"Cardiovascular disease as a leading cause of death: How are pharmacists getting involved?","volume":"8","author":"Alzubaidi","year":"2019","journal-title":"Integr. 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