Current evidence-based therapies for the treatment of diabetes and cardiac disease, including ACE inhibitors, Evofosfamide angiotensin receptor blockers , and statins have some intracellular antioxidant activity . Despite the abovementioned treatments and intensive glucose or blood pressure control, CHF remains a major public health burden with the need for new therapeutic strategies. Flavonols are plant-derived polyphenolic compounds that have been recognized to not only scavenge intracellular and extracellular ROS but to also inhibit enzymes responsible for the production of superoxide anions including xanthine oxidase, NADPH oxidase, cyclooxygenase, lipoxygenase, and protein kinase C . Recently, DiOHF , a small highly lipid soluble synthetic flavonol, has been demonstrated to attenuate myocardial ischemia/reperfusion injury, associated with its antioxidant activity . However, the antioxidant actions of orally administered DiOHF have yet to be tested in the setting of hyperglycemia-induced DCM. Accordingly, the present study aimed to examine the effects of DiOHF on cardiac function and structure in experimental DCM. The study was undertaken in the streptozotocin-induced PF-2341066 supplier transgenic m 27 rat, a hemodynamically validated model of diabetes-induced diastolic heart failure, which has been shown to develop structural and functional changes similar to that observed in human DCM . We demonstrated that DiOHF effectively reduced cardiac oxidative stress and was cardioprotective against cardiac dysfunction that develops as a consequence of diabetes. Clinically, DCM is characterized by early abnormalities in LV diastolic function that ultimately lead to chronic heart failure with subtle or no changes in LV systolic function . The most prominent cardiac remodelling event associated with these functional alterations is myocardial fibrosis with the accumulation of extracellular matrix components including collagen types I and III . The present study demonstrates that suppression of oxidative stress with DiOHF, a broad spectrum antioxidant, in an experimental model of diastolic heart failure due to diabetes, led to improved chamber compliance, reduced myocyte hypertrophy and collagen deposition. To our knowledge, this is the first study showing that oral antioxidant therapy with DiOHF prevents hyperglycemia-induced oxidative stressmediated myocardial injury and may represent a novel therapy to explore clinically. The pathogenesis of LV dysfunction in diabetic hearts has not been fully elucidated.