title: Eriodictyol-7-O-glucoside, a novel Nrf2 activator, confers protection against cisplatin-induced toxicity.
abstract: Eriodictyol-7-O-glucoside, a flavonoid isolated from Dracocephalum rupestre, is among the most potent free radical scavenger. In the present study, we identified eriodictyol-7-O-glucoside as a novel nuclear factor E2-related factor 2 (Nrf2) activator using a high-throughput cellular screening method. This compound activated Nrf2 signaling pathway and was able to stabilize Nrf2 by delaying Nrf2 degradation, resulting in accumulation of Nrf2 protein and activation of the Nrf2-dependent protective response. Recent studies have suggested that activation of Nrf2 pathway would confer protection against cisplatin-induced toxicity. The protective role of eriodictyol-7-O-glucoside in cisplatin-induced toxicity was investigated in a human renal mesangial cell line, HRMC. Cotreatment of HRMC cells with eriodictyol-7-O-glucoside significantly improved cell survival under cisplatin exposure. These findings demonstrated the feasibility of using natural compounds targeting Nrf2 as a therapeutic approach to subvert the side effects of cisplatin in normal cells.
authors.affiliation: Department of Natural Products Chemistry, School of Pharmaceutical Sciences, Shandong University, 44 Wenhuaxi Road, Jinan 250012, People's Republic of China.
authors.forename: Qingwen
authors.initials: Q
authors.lastname: Hu
authors.forename: Donna D
authors.initials: DD
authors.lastname: Zhang
authors.forename: Limei
authors.initials: L
authors.lastname: Wang
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Lou
authors.forename: Dongmei
authors.initials: D
authors.lastname: Ren
mesh_terms: D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors* / Q000633:toxicity; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000037:antagonists & inhibitors* / Q000633:toxicity; D044950:Flavanones / Q000494:pharmacology*; D017930:Genes, Reporter / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D010084:Oxidation-Reduction; D011506:Proteins / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000970:Antineoplastic Agents; D044950:Flavanones; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D011506:Proteins; D005978:Glutathione; D002945:Cisplatin; C007619:eriodictyol