{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:54:38Z","timestamp":1791593678832,"version":"4.3.4"},"reference-count":69,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T00:00:00Z","timestamp":1697241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deanship of Scientific Research at Princess Nourah bint Abdulrahman University through the Research Groups","award":["RGP-1441-0032 (2)"],"award-info":[{"award-number":["RGP-1441-0032 (2)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and\u00a0Objectives: This experiment evaluated the preventative influence of the tomato-derived Esculeoside A (ESA) on diabetic cardiomyopathy in type 1 diabetes mellitus (T1DM) in rats induced by streptozotocin (STZ). It also examined whether the activation of Nrf2 signaling affords this protection. Materials and Methods: Adult male Wistar control nondiabetic rats and rats with T1DM (STZ-T1DM) were given either carboxymethylcellulose as a vehicle or ESA (100 mg\/kg) (eight rats\/group) orally daily for 12 weeks. A group of STZ-T1DM rats was also treated with 100 mg\/kg ESA and co-treated i.p. with 2 mg\/kg (twice\/week), brusatol, and Nrf2 inhibitors for 12 weeks. Results and Conclusions: Treatment with ESA prevented the gain in heart weight and cardiomyocyte hypertrophy and improved the left ventricular (LV) systolic and diastolic function (LV) in the STZ-T1DM rat group. Likewise, it reduced their serum levels of triglycerides, cholesterol, and low-density lipoproteins (LDL-c), as well as their LV mRNA, cytoplasmic total, and nuclear total levels of NF-\u03baB. ESA also reduced the total levels of malondialdehyde, tumor necrosis factor-\u03b1, interleukine-6 (IL-6), Bax, cytochrome-c, and caspase-3 in the LV of the STZ-T1DM rats. In parallel, ESA enhanced the nuclear and cytoplasmic levels of Nrf2 and the levels of superoxide dismutase, glutathione, and heme oxygenase-1, but decreased the mRNA and cytoplasmic levels of keap-1 in the LVs of the STZ-T1DM rats. Interestingly, ESA did not affect the fasting insulin and glucose levels of the diabetic rats. All of these beneficially protective effects of ESA were not seen in the ESA-treated rats that received brusatol. In conclusion, ESA represses diabetic cardiomyopathy in STZ-diabetic hearts by activating the Nrf2\/antioxidant\/NF-\u03baB axis.<\/jats:p>","DOI":"10.3390\/medicina59101830","type":"journal-article","created":{"date-parts":[[2023,10,14]],"date-time":"2023-10-14T14:38:42Z","timestamp":1697294322000},"page":"1830","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Esculeoside A Decreases Diabetic Cardiomyopathy in Streptozotocin-Treated Rats by Attenuating Oxidative Stress, Inflammation, Fibrosis, and Apoptosis: Impressive Role of Nrf2"],"prefix":"10.3390","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5510-0768","authenticated-orcid":false,"given":"Jozaa Z.","family":"ALTamimi","sequence":"first","affiliation":[{"name":"Department of Physical Sports Sciences, College of Education, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9135-5725","authenticated-orcid":false,"given":"Nora A.","family":"AlFaris","sequence":"additional","affiliation":[{"name":"Department of Physical Sports Sciences, College of Education, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2043-1209","authenticated-orcid":false,"given":"Ghedeir M.","family":"Alshammari","sequence":"additional","affiliation":[{"name":"Department of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8515-1574","authenticated-orcid":false,"given":"Reham I.","family":"Alagal","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, College of Health and Rehabilitation Sciences, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalal H.","family":"Aljabryn","sequence":"additional","affiliation":[{"name":"Department of Physical Sports Sciences, College of Education, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5665-9600","authenticated-orcid":false,"given":"Mohammed Abdo","family":"Yahya","sequence":"additional","affiliation":[{"name":"Department of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/S2213-8587(22)00218-2","article-title":"Global incidence, prevalence, and mortality of type 1 diabetes in 2021 with projection to 2040: A modelling study","volume":"10","author":"Gregory","year":"2022","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"359","DOI":"10.2174\/1573399811666150724095130","article-title":"Diabetes mellitus in Saudi Arabia: A review of the recent literature","volume":"12","author":"Braham","year":"2016","journal-title":"Curr. 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