The interaction of pterostilbene with Kelch-like ECH-associated protein 1 and its regulation on the nuclear factor erythroid 2-related factor 2/antioxidant response element pathway

• Published in: Process biochemistry (1991) 2023-09, Vol.132, p.228-235
• Main Authors: Lv, Chengyu, Ma, Xinqi, Liang, Chengyu, Chen, Yihao, Qin, Fen, Zhou, Chuntian, Huang, Wei, Liu, Qing, Wang, Yongjun, Liu, Zhuo, Qin, Fengxian, Sun, Chang, Li, Tiezhu, Hou, Ligang
• Format: Article
• Language: English
• Subjects: Antioxidant; Keap1 protein; Nrf2-ARE pathway; Pterostilbene
• ISSN: 1359-5113; 1873-3298
• DOI: 10.1016/j.procbio.2023.07.009

Pterostilbene is a naturally occurring stilbene compound known for its anti-tumor effect. However, the molecular mechanism is still not explored well. Thus, the present work was designed to investigate the regulation effect of pterostilbene on the Nrf2-ARE pathway. The results of molecular docking showed that pterostilbene bound at the top of the central pore of the Keap1 Kelch domain, and the hydrogen bond and hydrophobic interactions were crucial for their stable binding. The western blot analysis confirmed that pterostilbene treatment promoted Nrf2 nuclear translocation. Reported gene assays confirmed the ARE luciferase activity of pterostilbene. RT-PCR and western blot assays showed that pterostilbene regulated the gene and protein expression of HO-1, NQO1, and GCLM. In vitro free radical scavenging assays have shown that pterostilbene can be effective in scavenging DPPH, ABTS, and hydroxyl radicals. In summary, pterostilbene activates the Nrf2-ARE pathway for exerting its bioactivities. [Display omitted] •Pterostilbene bound to the Keap1 Kelch structural domain.•Pterostilbene induced nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2).•Pterostilbene induced the gene and protein expressions of Nrf2-mediated targets.•Pterostilbene activates the Kepa1-Nrf2-ARE pathway for exerting its antioxidant activity.