Dehydro-Tocotrienol-β Counteracts Oxidative-Stress-Induced Diabetes Complications in db/db Mice

Abstract

Hyperglycemia, hyperlipidemia, and adiposity are the main factors that cause inflammation in type 2 diabetes due to excessive ROS production, leading to late complications. To counteract the effects of increased free radical production, we searched for a compound with effective antioxidant properties that can induce coenzyme Q biosynthesis without affecting normal cellular functions. Tocotrienols are members of the vitamin E family, well-known as efficient antioxidants that are more effective than tocopherols. Deh-T3β is a modified form of the naturally occurring tocotrienol-β. The synthesis of this compound involves the sequential modification of geranylgeraniol. In this study, we investigated the effects of this compound in different experimental models of diabetes complications. Deh-T3β was found to possess multifaceted capacities. In addition to enhanced wound healing, deh-T3β improved kidney and liver functions, reduced liver steatosis, and improved heart recovery after ischemia and insulin sensitivity in adipose tissue in a mice model of type 2 diabetes. Deh-T3β exerts these positive effects in several organs of the diabetic mice without reducing the non-fasting blood glucose levels, suggesting that both its antioxidant properties and improvement in mitochondrial function are involved, which are central to reducing diabetes complications.