Xanthohumol, a Polyphenol Chalcone Present in Hops, Activating Nrf2 Enzymes To Confer Protection against Oxidative Damage in PC12 Cells

Abstract

quinone oxidoreductase, thioredoxin, and thioredoxin reductase. A mechanistic study indicates that the α,β-unsaturated ketone structure in Xn and activation of the transcription factor Nrf2 are key determinants for the cytoprotection of Xn. Targeting the Nrf2 by Xn discloses a previously unrecognized mechanism underlying the biological action of Xn. Our results demonstrate that Xn is a novel small-molecule activator of Nrf2 in neuronal cells and suggest that Xn might be a potential candidate for the prevention of neurodegenerative disorders.

Synthesis of Piperlongumine Analogues and Discovery of Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) Activators as Potential Neuroprotective Agents

“…The NQO1 activity was determined spectrophotometrically by monitoring the reduction of the electron acceptor DCPIP at 600 nm. 13,14,62 The enzymatic reaction was initiated by the addition of cell lysate 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 28 protein extract, were prepared according to our previously published procedures. 1...…”

“…In this sense, activation of Nrf2-ARE pathway is a promising therapeutic approach in treatment of neurodegenerative disorders, 11,12 and thus the past years have witnessed the expanding interests in identifying and developing naturally occurring or synthetic small molecule activators of Nrf2-ARE pathway as potential neuroprotective agents. 6,[13][14][15][16] Natural products and their synthetic derivatives are invaluable fountain for therapeutic agents, and have driven pharmaceutical discovery over the past century. Piperlongumine (PL, Fig.…”

“…cultured cells was quantified by measuring LDH activity in the culture medium according to our published procedure 13,14. Hoechst 33342 staining.…”

“…The shRNA (shNrf2-842) targeting rat Nrf2 gene was used for Nrf2 knockdown experiments 13,14. The shRNA with scrambled sequence (shNT) was used as a control.…”

Targeting oxidative stress to treat endometriosis

“…Ther. Targets (2015) 19(10) lupulus) and is an active component in beer [116]. It is known for its antioxidant and anti-inflammatory effects and is therefore widely studied as an anticarcinogenic agent.…”