Effect and mechanism of Glabridin on cognitive impairment from MPTP to Parkinson's disease in mice
10.3969/j.issn.1008-9691.2024.02.010
- VernacularTitle:光甘草定对MPTP致帕金森病小鼠认知障碍的防治作用及其机制研究
- Author:
Yan ZHAO
1
;
Mengmeng SU
;
Lan DU
;
Yuan YAO
;
Runxiu ZHU
Author Information
1. 内蒙古自治区人民医院神经内科,内蒙古自治区 呼和浩特 010050
- Keywords:
Parkinson's disease;
Cognitive impairment;
Glabridin;
Extracellular regulated protein kinases;
Tyrosine hydroxylase
- From:
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care
2024;31(2):178-183
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the improving effect and mechanism of the traditional Chinese herbal medicine Glabridin(GLA)on cognitive impairment in Parkinson's disease(PD)mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP),and its protective effect on the cerebral cortex and hippocampus through affecting the extracellular regulated protein kinases(ERK)signaling pathway involved in the regulation of neural plasticity.Methods A total of 120 C57BL//6N mice were randomly divided into control group,model group,GLA control group and MPTP+GLA low,medium and high-dose groups,with 20 mice in each group.The mouse PD model was established by intraperitoneal injection of MPTP 20 mg/kg,and the control group was injected with the same dose of normal saline.The GLA control group was given 50 mg/kg GLA by gavage;the MPTP+GLA low,medium and high dose groups were given 20,30 and 50 mg/kg GLA by gavage 1 hour after each MPTP administration,once a day for 7 consecutive days.The learning and memory abilities of the mice in each group and the pathological changes of hippocampal tissue were observed,as well as the changes in the contents of tumor necrosis factor-α(TNF-α),interleukin-18(IL-18),malondialdehyde(MDA),superoxide dismutase(SOD),tyrosine hydroxylase(TH)and protein expression levels of phosphorylated-ERK 1/2(p-ERK1/2)in the cerebral cortex.Results Compared with the control group,the levels of MDA and TNF-α,IL-18 in the cerebral cortex of the model group were significantly increased[MDA(nmol/mg):4.68±0.51 vs.2.05±0.22,TNF-α(μg/L):116.87±15.65 vs.48.52±7.83,IL-18(μg/L):57.52±6.89 vs.24.26±1.89,all P<0.05],while the activity of SOD was significantly decreased(U/mg:77.84±7.84 vs.130.89±18.56,P<0.05).Compared with the model group,the contents of TNF-α,IL-18,and MDA in each MPTP+GLA group were significantly decreased,while the activity of SOD was significantly increased(all P<0.05),and the change in the high-dose MPTP+GLA group was more obvious.The learning and memory ability of the high-dose MPTP+GLA group was significantly improved,the number of neurons in the hippocampus tissue decreased,the neurodegeneration was improved,and the glial cell proliferation was reduced.The results of immunohistochemistry showed that compared with the model group,the loss of TH positive cells in the high-dose MPTP+GLA group was significantly reduced[absorbance(A value):cerebral cortex was 39.14±3.25 vs.23.14±3.1,hippocampus was 72.14±4.25 vs.52.16±3.32,both P<0.05],and the expression of p-ERK1/2 positive cells was significantly inhibited(A value:cerebral cortex was 63.91±3.55 vs.88.35±6.41,hippocampus was 73.36±3.52 vs.93.25±6.73,both P<0.05).Western blotting showed that compared with the model group,the protein expression level of cerebral cortex and hippocampus TH in the high-dose MPTP+GLA group was significantly increased(gray value:cerebral cortex was 0.71±0.09 vs.0.53±0.06,hippocampus was 0.68±0.06 vs.0.45±0.03,both P<0.05),and the protein expression level of p-ERK1/2 was significantly inhibited(gray value:cerebral cortex was 0.76±0.10 vs.0.96±0.08,hippocampus was 0.74±0.06 vs.0.96±0.12,both P<0.05).Conclusions The traditional Chinese medicine GLA can improve the learning and memory ability of MPTP-induced PD mice,as well as prevent and treat MPTP-induced neuronal damage and glial cell proliferation.The ERK signaling pathway is associated with neural damage in PD brain tissue.GLA protects the learning and memory ability of MPTP-induced PD mice by inhibiting the ERK signaling pathway.
