Eriodictyol-7-O-glucoside, a novel Nrf2 activator, confers protection against cisplatin-induced toxicity

• Published in: Food and chemical toxicology Vol. 50; no. 6; pp. 1927 - 1932
• Main Authors: Hu, Qingwen, Zhang, Donna D., Wang, Limei, Lou, Hongxiang, Ren, Dongmei
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-06-2012; Elsevier
• Subjects: Activate; adverse effects; Antineoplastic Agents - antagonists & inhibitors; Antineoplastic Agents - toxicity; Biological and medical sciences; Blotting, Western; Cell Line; Cell survival; Cell Survival - drug effects; cell viability; Cisplatin; Cisplatin - antagonists & inhibitors; Cisplatin - toxicity; Dracocephalum; Eriodictyol-7-O-glucoside; Flavanones - pharmacology; flavonoids; free radical scavengers; Genes, Reporter - drug effects; Glutathione - metabolism; Half-Life; Humans; Medical sciences; NF-E2-Related Factor 2 - metabolism; Nrf2; Oxidation-Reduction; protective effect; Proteins - metabolism; Real-Time Polymerase Chain Reaction; screening; signal transduction; Toxicity; Toxicology; NQO1; Eriodictyol-7-O-glucoside; ARE; Nrf2; Activate; Toxicity; ROS; Keap1; HO-1; Cisplatin; Antineoplastic agent; Biochemical compound; Glucoside; Oside; Prevention; Alkylating agent; Activator; Carbohydrate; Glycoside; Heteroside; Platinum II Complexes
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2012.03.059

Eriodictyol-7-O-glucoside was identified as a novel Nrf2 activator and the present study demonstrated the efficacy of the compound in battling cisplatin-induced toxicity. [Display omitted]
► Eriodictyol-7-O-glucoside (E7G) was identified as a novel Nrf2 activator. ► E7G was able to stabilize Nrf2 by delaying Nrf2 degradation. ► E7G significantly improved HRMC cell survival under cisplatin exposure.
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.