Abstract
Oxidative stress and inflammation are significant risk factors for neurodegenerative disease. The Keap1-Nrf2-ARE pathway is one of the most promising defensive systems against oxidative stress. Here, dozens of piperlongumine analogues were designed, synthesized, and tested on PC12cells to examine neuroprotective effects against H2O2 and 6-OHDA induced damage. Among them, 6d was found to be able to alleviate the accumulation of ROS, inhibit the production of NO and downregulate the level of IL-6, which indicated its potential antioxidant and anti-inflammatory activity. Further studies proved that 6d could activate Nrf2 signaling pathway, induce the translocation of Nrf2 from cell cytosol to nucleus and upregulate the related phase II antioxidant enzymes including NQO1, HO-1, GCLC, GCLM and TrxR1. These results confirmed that 6d exerted antioxidant and anti-inflammatory activities by activating Nrf2 signaling pathway. Moreover, the parallel artificial membrane permeability assay indicated that 6d can cross the blood-brain barrier. In general, 6d is promising for further development as a therapeutic drug against oxidative stress and inflammation related neurodegenerative disorders.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
