Crocin Inhibited Aβ Generation via Modulating APP Processing, Suppressing Endoplasmic Reticulum Stress and Activating Autophagy in N2a/APP Cells.
10.1007/s11655-025-3933-7
- Author:
Zi-Rong LIANG
1
;
Cui-Jun LIN
1
;
Yi-Han LIU
1
;
Qian YUE
1
;
Pui Man HOI
2
Author Information
1. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR, 999078, China.
2. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR, 999078, China. maghoi@um.edu.mo.
- Publication Type:Journal Article
- Keywords:
Alzheimer’s disease;
amyloid precursor protein processing;
autophagy;
crocin;
endoplasmic reticulum stress;
unfolded protein response
- MeSH:
Endoplasmic Reticulum Stress/drug effects*;
Autophagy/drug effects*;
Animals;
Endoplasmic Reticulum Chaperone BiP;
Mice;
Amyloid beta-Peptides/metabolism*;
Amyloid beta-Protein Precursor/metabolism*;
Carotenoids/pharmacology*;
Humans;
Cell Line, Tumor;
Reactive Oxygen Species/metabolism*;
Apoptosis/drug effects*;
Calcium/metabolism*
- From:
Chinese journal of integrative medicine
2025;31(11):973-981
- CountryChina
- Language:English
-
Abstract:
OBJECTIVE:To explore the mechanism of crocin, a major active component of Crocus sativus (Zanghonghua), in regulating amyloid beta (Aβ) generation, endoplasmic reticulum (ER) stress, and autophagy in neuronal cells, with potential therapeutic applications in Alzheimer's disease (AD).
METHODS:Mouse neuroblastoma Neuron2a (N2a) cells stably transfected with the human amyloid precursor protein (APP) Swedish mutant was used as a cellular model for AD (N2a/APP). Control cells were vector transfected (N2a/vector). The effects of 3 different doses of crocin on reactive oxygen species (ROS) generation, cytosolic calcium, and apoptosis were evaluated by flow cytometry. Aβ levels were determined by enzyme-linked immunosorbent assay. APP processing and ER stress proteins expressions were determined by Western blot. Autophagosome formation was evaluated by autophagy detection kit and confocal microscope.
RESULTS:Crocin inhibited APP expression in N2a/APP cells and promoted α-cleavage of APP processing, while modestly reduced beta-secretase 1 (BACE1) and presenilin 1 (PS1, P<0.05 or P<0.01). ER stress markers, including the binding immunoglobulin protein/78-kD glucose-regulated protein (Bip/GRP78) and C/EBP homologous protein (CHOP), were elevated in N2a/APP cells compared to N2a/vector cells (P<0.05). Crocin could effectively reduce the levels of ER stress (P<0.05 or P<0.01). In addition, crocin enhanced autophagy by promoting formation of autophagosome (P<0.05 or P<0.01).
CONCLUSION:Crocin significantly inhibited Aβ generation by promoting α-cleavage of APP processing, inhibiting ER stress-associated unfolded protein response, and regulating autophagy.
