Mechanism of Congrong Zonggan Capsules in Improving Neuroinflammation and Cognitive Impairment in 5×FAD Mice Based on NF-κB/NLRP3 Signaling Pathway
10.13422/j.cnki.syfjx.20250305
- VernacularTitle:基于NF-κB/NLRP3信号通路探讨苁蓉总苷胶囊改善5×FAD小鼠神经炎症及认知功能障碍机制
- Author:
Yanru ZHOU
1
;
Xinru GU
1
;
Yuru LIU
1
;
Shun ZHANG
1
;
Yaozhong LYU
1
;
Zhenzhong WANG
1
Author Information
1. State Key Laboratory of Technologies for Chinese Medicine Pharmaceutical Process Control and Intelligent Manufacture，Nanjing University of Chinese Medicine，Jiangsu Kanion Pharmaceutical Co. Ltd.，Nanjing 210000，China
- Publication Type:Journal Article
- Keywords:
Congrong Zonggan capsules;
Alzheimer's disease;
neuroinflammation;
microglia;
cognitive impairment
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(10):130-138
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the effects of Congrong Zonggan capsules （CRZG） on cognitive impairment in the Alzheimer's disease （AD） model of mice and its related mechanisms. MethodsSPF grade 4-week-old 5×FAD mice were divided into a model group， low-dose CRZG （0.819 g·kg-1） and high-dose CRZG （1.638 g·kg-1） groups， and Donepezilepezil hydrochloride group （2 mg·kg-1）， with eight mice in each group. Eight C57 mice with the same background were set as the normal group. After one week of adaptive feeding， mice were orally administered continuously for six months. On the 5th month of drug administration， Y maze， new object recognition， and Morris water maze tests were conducted separately. After administration， mouse brain tissue was taken， and the levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in brain tissue were detected by enzyme-linked immunosorbent assay （ELISA）. Immunofluorescence （IF） was used to detect the expression of small glial cell markers Iba1， astrocyte markers GFAP， and amyloid protein 1-42 （Aβ1-42） in the hippocampus of the brain tissue. The hematoxylin-eosin （HE） staining was used to detect pathological changes in the hippocampus of brain tissue. Western blot was used to detect the expression of nuclear factor-κB （NF-κB） p65， NOD-like receptor protein 3 （NLRP3）， cleaved Caspase-1， apoptosis-associated speck-like protein containing a CARD （ASC）， and other proteins in the brain tissue. ResultsCompared with those in the normal group， the mice in the model group had obvious cognitive impairment. The spontaneous alternation rate of the Y maze was decreased， and the discrimination index of novel object recognition was decreased significantly （P<0.01）. The escape latency in the water maze was shortened significantly （P<0.01）. The contents of IL-6 and TNF-α in brain tissue were increased. The fluorescence levels of Iba1 and Aβ1-42 in the hippocampus were significantly increased （P<0.01）. There was a significant increase in neuronal lesions， neuronal atrophy， loose arrangement of tissue structure， and abnormal erythrocyte aggregation in the hippocampus. The protein expressions of p-NF-κB p65/NF-κB p65， cleaved Caspase-1， ASC， IL-6， and IL-1β were significantly increased （P<0.05， P<0.01）. Compared with the model group， the spontaneous alternation rate and discrimination index of the high-dose CRZG group were increased significantly （P<0.01）， and the escape latency was shortened significantly （P<0.05， P<0.01）. The content of IL-6 decreased in the brain， and that of TNF-α dropped significantly （P<0.01）. The expression of Iba1 protein and Aβ1-42 in the hippocampus decreased significantly （P<0.05， P<0.01）. The hippocampal neurons were densely arranged， and the pyramidal nuclei were clear and centered. The abnormal aggregation of red blood cells was alleviated. The value of p-NF-κB/NF-κB proteins and the expression of ASC， cleaved Caspase-1， IL-6， and IL-1β were significantly decreased （P<0.05， P<0.01）. ConclusionCRZG can effectively improve cognitive impairment in 5×FAD mice with Alzheimer's disease， and its mechanism may be related to the regulation of the NF-κB/NLRP3 pathway to reduce the abnormal activation of microglia and inhibit neuroinflammation.
