Issue 18, 2024

Dietary bitter ginger-derived zerumbone improved memory performance during aging through inhibition of the PERK/CHOP-dependent endoplasmic reticulum stress pathway

Abstract

PERK/CHOP pathway-mediated excessive endoplasmic reticulum (ER) stress is closely linked to aging-related cognitive impairment (ARCD). Zerumbone (ZB), a naturally occurring sesquiterpene molecule obtained from dietary bitter ginger, has garnered significant interest due to its diverse range of biological properties. It is unclear, though, if ZB can reduce ARCD by preventing ER stress that is dependent on the PERK/CHOP pathway. Here, the PERK-CHOP ER stress pathway was the main focus of an evaluation of the effects and mechanisms of ZB for attenuating ARCD in D-galactose (D-gal)-induced aging mice and SH-SY5Y cells. According to our findings, ZB not only greatly decreased neuronal impairment both in vitro and in vivo, but also significantly alleviated learning and memory failure in vivo. ZB significantly reduced the activation of the PERK/CHOP pathway and neuronal apoptosis in vitro and in vivo, exhibiting the down-regulation of GRP78, p-PREK/PERK, and CHOP expression levels, in addition to suppressing oxidative damage (MDA drop and SOD rise). Comparable outcomes were noted in SH-SY5Y cells subjected to severe ER stress caused by TM. On the other hand, 4-PBA, an ER stress inhibitor, considerably reversed these modifications. Remarkably, CCT020312 (a PERK activator) dramatically overrode the inhibitory effects of ZB on the PERK/CHOP pathway and neuronal death in D-gal-induced SH-SY5Y cells. In contrast, GSK2606414 (a PERK inhibitor) significantly increased these effects of ZB. In summary, our results suggested that ZB prevented D-gal-induced cognitive deficits by blocking the PERK/CHOP-dependent ER stress pathway and apoptosis, suggesting that ZB might be a natural sesquiterpene molecule that relieves ARCD.

Graphical abstract: Dietary bitter ginger-derived zerumbone improved memory performance during aging through inhibition of the PERK/CHOP-dependent endoplasmic reticulum stress pathway

Supplementary files

Article information

Article type
Paper
Submitted
26 Jan 2024
Accepted
16 Jul 2024
First published
30 Jul 2024

Food Funct., 2024,15, 9070-9084

Dietary bitter ginger-derived zerumbone improved memory performance during aging through inhibition of the PERK/CHOP-dependent endoplasmic reticulum stress pathway

C. Yang, M. Zhao, Y. Chen, J. Song, D. Wang, M. Zou, J. Liu, W. Wen and S. Xu, Food Funct., 2024, 15, 9070 DOI: 10.1039/D4FO00402G

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