Dietary prenylated flavonoid xanthohumol alleviates oxidative damage and accelerates diabetic wound healing via Nrf2 activation. (February 2022)

• Record Type: Journal Article
• Authors: Lu, Xuxiu; Liu, Mingfei; Dong, Hui; Miao, Jinlai; Stagos, Dimitrios; Liu, Ming
• Is Part Of: Food and chemical toxicology. Volume 160(2022)
• Publication Date: 2022-02
• Subjects: AMPKα -- Diabetic wound healing -- Nrf2 -- Oxidative stress -- XN; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2022.112813
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: Diabetic skin ulcer is one of the most common complications in patients suffering diabetes mellitus. Xanthohumol (XN), a hop-derived prenylated dietary flavonoid, has multiple health beneficial bioactivities. In the present study, we reported XN alleviates oxidative damage and accelerates diabetic wound healing via Nrf2 activation. In vitro, XN attenuated hydrogen peroxide (H2 O2 )-induced cytotoxicity, ROS production, cell apoptosis, as well as high glucose-induced cell damage. Mechanistic studies further demonstrated that XN could stabilize nuclear factor erythroid 2-related factor 2 (Nrf2) and promote its nuclear translocation, which was associated with AMPKα activation and covalent modification of Keap1 by XN. In vivo, XN increased Nrf2 expression and accelerated diabetic wound healing. Our study revealed a novel function of XN in diabetic wound healing as well as the underlying molecular mechanisms, suggesting XN is a promising lead compound and a potential food and/or drug candidate for the treatment of diabetic skin ulcers. Graphical abstract: Image 1 Highlights: Xanthohumol (XN) exhibited the endothelial and epidermal protective effect. XN demonstrated significant antioxidant activity both in vitro and in vivo . Nrf2 activation was involved in XN-promoted diabetic wound healing. XN-induced Nrf2 activation was associated with AMPKα activation.