Effect of Erjing Pills on alleviating neuroinflammation of AD rats based on TLR4/NF-κB/NLRP3 pathway and its mechanism.
10.19540/j.cnki.cjcmm.20221014.704
- Author:
Li-Ping HUANG
1
;
Long-Hui LU
2
;
Xi-Yang YANG
3
;
Yong-Yan XIE
2
;
Zi-Wei XU
2
;
Xu-Dong ZHU
2
;
Jing-Jing WANG
2
;
Zhi-Xin WU
2
;
Jian-Fu TANG
2
;
Yi WU
4
;
Yao-Hui CHEN
5
Author Information
1. School of Pharmacy,Jiangxi University of Chinese Medicine Nanchang 330004,China Key Laboratory of TCM Pharmacology of Jiangxi Province Nanchang 330004,China.
2. School of Pharmacy,Jiangxi University of Chinese Medicine Nanchang 330004,China.
3. School of Pharmacy,Jiangxi University of Chinese Medicine Nanchang 330004,China the First Hospital of Putian City Putian 351199,China.
4. NMPA Key Laboratory of Quality Evaluation of Traditional Chinese Patent Medicine,Jiangxi Provincial Engineering Research Center for Drug and Medical Device Quality,Jiangxi Institute for Drug Control Nanchang 330046,China.
5. Jiangxi Provincial People's Hospital Nanchang 330029,China.
- Publication Type:Journal Article
- Keywords:
Alzheimer′s disease;
Erjing Pills;
TLR4/NF-κB/NLRP3 pathway;
microglia;
neuroinflammation
- MeSH:
Animals;
Rats;
Rats, Sprague-Dawley;
NF-kappa B;
NF-KappaB Inhibitor alpha;
NLR Family, Pyrin Domain-Containing 3 Protein;
Galactose;
Interleukin-6;
Neuroinflammatory Diseases;
Toll-Like Receptor 4;
Tumor Necrosis Factor-alpha
- From:
China Journal of Chinese Materia Medica
2023;48(3):770-777
- CountryChina
- Language:Chinese
-
Abstract:
This paper aimed to study the effect of Erjing Pills on the improvement of neuroinflammation of rats with Alzheimer's di-sease(AD) induced by the combination of D-galactose and Aβ_(25-35) and its mechanism. SD rats were randomly divided into a sham group, a model control group, a positive drug group(donepezil, 1 mg·kg~(-1)), an Erjing Pills high-dose group(9.0 g·kg~(-1)), and an Erjing Pills low-dose group(4.5 g·kg~(-1)), with 14 rats each group. To establish the rat model of AD, Erjing Pills were intragastrically administrated to rats for 5 weeks after 2 weeks of D-galactose injection. D-galactose was intraperitoneally injected into rats for 3 weeks, and then Aβ_(25-35) was injected into the bilateral hippocampus. The new object recognition test was used to evaluate the learning and memory ability of rats after 4 weeks of intragastric administration. Tissues were acquired 24 h after the last administration. The immunofluorescence method was used to detect the activation of microglia in the brain tissue of rats. The positive expressions of Aβ_(1-42) and phosphory protein Tau~(404)(p-Tau~(404)) in the CA1 area of the hippocampus were detected by immunohistochemistry. The levels of inflammatory factors interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6) in the brain tissue were determined by enzyme-linked immunosorbent assay(ELISA). Toll-like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)/nucleotide-binding oligomerization domain-like receptors 3(NLRP3) pathway-associated proteins in the brain tissue were determined by Western blot. The results showed that as compared with the sham group, the new object recognition index of rats in the model control group decreased significantly, the deposition of Aβ_(1-42) and p-Tau~(404) positive protein in the hippocampus increased significantly, and the levels of microglia activation increased significantly in the dentate gyrus. The levels of IL-1β, TNF-α, and IL-6 in the hippocampus of the model control group increased significantly, and the expression levels of TLR4, p-NF-κB p65/NF-κB p65, p-IκBα/IκBα, and NLRP3 proteins in the hippocampus increased significantly. Compared with the model control group, the Erjing Pill groups enhanced the new object recognition index of rats, decreased the deposition of Aβ_(1-42) and the expression of p-Tau~(404) positive protein in the hippocampus, inhibited the activation of microglia in the dentate gyrus, reduced the levels of inflammatory factors IL-1β, TNF-α, and IL-6 in the hippocampus, and down-regulated the expression levels of TLR4, p-NF-κB P65/NF-κB P65, p-IκBα/IκBα, and NLRP3 proteins in the hippocampus. In conclusion, Erjing Pills can improve the learning and memory ability of the rat model of AD presumably by improving the activation of microglia, reducing the expression levels of neuroinflammatory factors IL-1β, TNF-α, and IL-6, inhibiting the TLR4/NF-κB/NLRP3 neuroinflammation pathway, and decreasing hippocampal deposition of Aβ and expression of p-Tau, thereby restoring the hippocampal morphological structure.
