title: Hepatoprotective effect of 7-Hydroxycoumarin against Methyl glyoxal toxicity via activation of Nrf2.
abstract: Methyl glyoxal (MG), a major precursor of advanced glycation end-products, has been identified as significant in the progression of several diseases including aging, diabetes and neurodegenerative diseases as well as causing hepatic damages. 7-hydroxycoumarin (7-HC), a natural-occurring derivative of coumarin from fruits and plants, has been reported to exert antioxidant and free radical-scavenging properties, protecting cells from aldehydes and oxidants. In this study, the ability of 7-HC to protect human HepG2 cells against MG-induced toxicity and oxidative stress was investigated. Results show that 7-HC pretreatment significantly attenuates MG-induced cytotoxicity, apoptotic changes and ROS accumulation and that this protection is shown to be associated with the induction of the nuclear factor erythroid 2-related factor 2 (NRF2) and its downstream detoxifying enzymes. In response to 7-HC, NRF2 protein translocates from cytosol to the nuclei. In addition, depletion of NRF2 by siRNA significantly reduces the protective effect of 7-HC against MG, suggesting that NRF2 plays an important role in the protective function of 7-HC. These findings highlight the potential for the interventional activation of the NRF2 induction via the non-toxic natural phytochemical 7-HC as a novel therapeutic approach towards the detoxification of MG, with the aim of halting the progression of diseases in which MG has been implicated.
authors.affiliation: Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, 310014, China; Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow, G4 0RE, United Kingdom. Electronic address: lidan@zjut.edu.cn.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, 310014, China.
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Cancer Hospital of China Medical University, Shenyang, 110001, China.
authors.forename: Jingdong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Endoscope, The General Hospital of Shenyang Military Region, Shenyang, 110016, China.
authors.forename: Shuren
authors.initials: S
authors.lastname: Ma
authors.affiliation: Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, 310014, China.
authors.forename: Zhuangzhuang
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow, G4 0RE, United Kingdom.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Ellis
mesh_terms: D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020011:Protective Agents / Q000494:pharmacology*; D011765:Pyruvaldehyde / Q000737:chemistry / Q000633:toxicity*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014468:Umbelliferones / Q000494:pharmacology*
chemical_list: D051267:NF-E2-Related Factor 2; D020011:Protective Agents; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D014468:Umbelliferones; C031477:7-hydroxycoumarin; D011765:Pyruvaldehyde; D053148:Caspase 3; D053179:Caspase 7
keywords: 7-Hydroxycoumarin; Chemoprevention; Hepatotoxicity; Methyl glyoxal; NRF2