Neuroprotective Effect of Baicalein in Parkinson's Disease Model Rats and Its Impact on PERK/ATF4 Endoplasmic Reticulum Stress Pathway
10.13422/j.cnki.syfjx.20252237
- VernacularTitle:黄芩素对帕金森病模型大鼠的神经功能保护作用及对PERK/ATF4内质网应激通路的影响
- Author:
Ziqi ZHANG
1
;
Jingfeng OUYANG
1
Author Information
1. Experimental Research Center， China Academy of Chinese Medical Sciences， Beijing 100700，China
- Publication Type:Journal Article
- Keywords:
baicalein;
Parkinson's disease;
endoplasmic reticulum stress;
apoptosis;
neuroprotective effect
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(8):74-81
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the neuroprotective mechanism of baicalein （BAI） on Parkinson's disease （PD） model rats by regulating endoplasmic reticulum stress pathway. MethodsSeventy-two Sprague-Dawley （SD） rats were randomly divided into normal group， model group， BAI low-dose group （80 mg·kg-1）， medium-dose group （120 mg·kg-1）， high-dose group （160 mg·kg-1）， and levodopa-benserazide group （51 mg·kg-1）， with 12 rats per group. Except for the normal group， PD rat models were established by subcutaneous injection of rotenone solution （2 mg·kg-1） into the neck back of rats in the rest of groups for consecutive 28 days. Concurrently， rats in all groups received corresponding drugs via gavage for 28 days. After treatment， behavioral changes were assessed by using the open field and pole climbing tests. Neuronal pathology and apoptosis in the substantia nigra were observed via hematoxylin-eosin （HE） staining and TdT-mediated dUTP nick-end labeling （TUNEL） assay. α-Synuclein and tyrosine hydroxylase （TH） expressions were detected by immunohistochemistry （IHC）. Inflammatory factors such as interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） were measured by enzyme-linked immunosorbent assay （ELISA）. RNA-like endoplasmic reticulum kinase （PERK）， activating transcription factor 4 （ATF4）， C/EBP-homologous protein （CHOP）， and Bcl-2-associated X protein （Bax） expressions were analyzed by Western blot. ResultsCompared with the normal group， the model group exhibited significantly reduced locomotion distance （P<0.01） and elevated pole-climbing scores （P<0.01）， with increased neuronal apoptosis rate （P<0.01）， significantly enhanced α-Synuclein expression （P<0.01）， decreased TH expression （P<0.01）， upregulated release of inflammatory factors （P<0.05，P<0.01）， and increased protein expressions of PERK/ATF4 pathway proteins and pro-apoptotic Bax （P<0.05，P<0.01）. Compared with the model group， medium/high-dose BAI groups and levodopa-benserazide group showed obviously improved motor function （P<0.05，P<0.01）， reduced pole-climbing scores （P<0.05）， decreased neuronal apoptosis （P<0.01）， downregulated α-Synuclein expression （P<0.01）， upregulated TH expression （P<0.05，P<0.01）， suppressed release of inflammatory factors （P<0.05，P<0.01）， and decreased protein expressions of PERK/ATF4 pathway proteins and pro-apoptotic Bax （P<0.05，P<0.01）. ConclusionBAI reduces the release of neuroinflammatory factors and neuronal apoptosis to improve the neurological function of PD model rats， and its mechanism may be related to alleviating endoplasmic reticulum stress and apoptosis by regulating the PERK/ATF4 pathway.
