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

被引:0
作者
Yang, Chuan [1 ,2 ,3 ]
Zhao, Meihuan [1 ,2 ,3 ]
Chen, Yuanyuan [1 ,2 ,3 ]
Song, Juxian [1 ,2 ,3 ]
Wang, Dan [2 ,4 ]
Zou, Mi [2 ,4 ]
Liu, Jingru [5 ]
Wen, Wen [1 ,2 ,3 ]
Xu, Shijun [1 ,2 ,3 ]
机构
[1] Chengdu Univ Tradit Chinese Med, State Key Lab Southwestern Chinese Med Resources, Chengdu 611137, Peoples R China
[2] Chengdu Univ Tradit Chinese Med, Inst Mat Med Integrat & Transformat Brain Disorder, Chengdu 611137, Peoples R China
[3] Chengdu Univ Tradit Chinese Med, Sch Pharm, Chengdu 611137, Peoples R China
[4] Chengdu Univ Tradit Chinese Med, Sch Hlth Preservat & Rehabil, Chengdu 611137, Peoples R China
[5] UCL, Gower St, London WC1E 6BT, England
关键词
UNFOLDED PROTEIN RESPONSE; ER STRESS; CELLS; PROTEOSTASIS; IMPAIRMENT; ACTIVATION; CASPASE-12; APOPTOSIS; SURVIVAL;
D O I
10.1039/d4fo00402g
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. Zerumbone rescued aging-related cognitive deficits (ARCD) through inhibiting the PERK/CHOP-dependent excessive endoplasmic reticulum (ER) stress.
引用
收藏
页码:9070 / 9084
页数:16
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