title: Potential drugs which activate nuclear factor E2-related factor 2 signaling to prevent diabetic cardiovascular complications: A focus on fumaric acid esters.
abstract: Diabetes and its cardiovascular complications have been a major public health issue. These complications are mainly attributable to a severe imbalance between free radical and reactive oxygen species production and the antioxidant defense systems. Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor that controls the basal and inducible expression of a battery of antioxidant enzyme genes and other cyto-protective phase II detoxifying enzymes. As a result, Nrf2 has gained great attention as a promising drug target for preventing diabetic cardiovascular complications. And while animal studies have shown that several Nrf2 activators manifest a potential to efficiently prevent the diabetic complications, their use in humans has not been approved due to the lack of substantial evidence regarding safety and efficacy of the Nrf2 activation. We provide here a brief review of a few clinically-used drugs that can up-regulate Nrf2 with the potential of extending their usage to diabetic patients for the prevention of cardiovascular complications and conclude with a closer inspection of dimethyl fumarate and its mimic members.
authors.affiliation: Department of Cardiovascular Diseases, the First Hospital of Jilin University, Changchun 130021, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Endoscopy Center China-Japan Union Hospital of Jilin University, 126 Xiantai Street, Changchun 130033, China.
authors.forename: Jingpeng
authors.initials: J
authors.lastname: Jin
authors.affiliation: Department of Cardiovascular Diseases, the First Hospital of Jilin University, Changchun 130021, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Bai
authors.affiliation: Kosair Children's Hospital Research Institute at the Department of Pediatrics of the University of Louisville, Louisville 40202, USA.
authors.forename: Leroy R
authors.initials: LR
authors.lastname: Sachleben
authors.affiliation: Kosair Children's Hospital Research Institute at the Department of Pediatrics of the University of Louisville, Louisville 40202, USA. Electronic address: l0cai001@louisville.edu.
authors.forename: Lu
authors.initials: L
authors.lastname: Cai
authors.affiliation: Department of Cardiovascular Diseases, the First Hospital of Jilin University, Changchun 130021, China. Electronic address: zhengyang@jlu.edu.cn.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D003879:Dermatologic Agents / Q000494:pharmacology*; D058065:Diabetic Cardiomyopathies / Q000188:drug therapy / Q000378:metabolism*; D000069462:Dimethyl Fumarate; D005650:Fumarates / Q000494:pharmacology*; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D003879:Dermatologic Agents; D005650:Fumarates; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D000069462:Dimethyl Fumarate
keywords: Bardoxolone; Diabetic complications; Dimethyl fumarate; Nrf2; Oxidative stress; Sulforaphane