Cannabidiol inhibits neuronal endoplasmic reticulum stress and apoptosis in rats with multiple concussions by regulating the PERK-eIF2α-ATF4-CHOP pathway.
10.12122/j.issn.1673-4254.2025.06.13
- Author:
Yujia YANG
1
;
Lifang YANG
1
;
Yaling WU
1
;
Zhaoda DUAN
1
;
Chunze YU
1
;
Chunyun WU
1
;
Jianyun YU
2
;
Li YANG
1
Author Information
1. Department of Human Anatomy and Histology & Embryology, Faculty of Basic Medical Sciences, Shuozhou Maternal and Child Health Hospital, Shuozhou 036000, China.
2. Department of Ultrasound, Shuozhou Maternal and Child Health Hospital, Shuozhou 036000, China.
- Publication Type:Journal Article
- Keywords:
PERK signaling pathway;
cannabidiol;
endoplasmic reticulum stress;
multiple cerebral concussions;
neuronal apoptosis
- MeSH:
Animals;
Endoplasmic Reticulum Stress/drug effects*;
Apoptosis/drug effects*;
Rats, Sprague-Dawley;
Activating Transcription Factor 4/metabolism*;
Transcription Factor CHOP/metabolism*;
Rats;
Eukaryotic Initiation Factor-2/metabolism*;
Signal Transduction/drug effects*;
eIF-2 Kinase/metabolism*;
Cannabidiol/pharmacology*;
Neurons/metabolism*;
Brain Concussion/metabolism*;
Male;
Molecular Docking Simulation
- From:
Journal of Southern Medical University
2025;45(6):1240-1250
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES:To explore the effects of cannabidiol on endoplasmic reticulum stress and neuronal apoptosis in rats with multiple concussions (MCC).
METHODS:SD rats were randomized into sham group, MCC group, 1% tween20 (TW) treatment group, and low-dose (10 mg/kg) and high-dose (40 mg/kg) cannabidiol treatment groups. In all but the sham group, MCC models were established using a metal pendulum percussion device, after which the rats received daily intraperitoneal injections of the corresponding agents for 2 weeks. The expressions of PERK, eIF2α, ATF4, CHOP, TRIB3, p-Akt and pro-caspase-3 in the brain tissue of the rats were detected with qRT-PCR, Western blotting and immunofluorescence staining. The core targets of cannabidiol in treatment of traumatic brain injury (TBI) were identified by network pharmacology analysis, and molecular docking was carried out to simulate the interaction of cannabidiol with the factors related to endoplasmic reticulum stress and apoptosis.
RESULTS:Compared with the sham-operated rats, the rat models of MCC showed significantly increased mRNA expressions of PERK, eIF2α and CHOP and protein expressions of PERK, eIF2α, ATF4, CHOP, TRIB3, p-AKT and pro-caspase-3 in the cerebral cortex. CBD treatment, especially at the high dose, obviously increased the expression of p-Akt and lowered the expression levels of the other factors tested in the rat models. Network pharmacology analysis indicated interactions of the core targets of CBD with the factors related to endoplasmic reticulum stress and TBI, and molecular docking study showed a high binding energy of CBD with multiple factors pertaining to endoplasmic reticulum stress and apoptosis.
CONCLUSIONS:MCC induce endoplasmic reticulum stress and apoptosis in rat brain tissues, for which CBD, especially at a high dose, provides neuroprotective effects by inhibiting endoplasmic reticulum stress and cell apoptosis.
