Protective effect of Liujing Toutong Tablets on rats with permanent cerebral ischemia via NF-κB signaling pathway.
10.19540/j.cnki.cjcmm.20230710.705
- Author:
Zi-Han YU
1
;
Ke PEI
1
;
Ting-Ting ZHAO
1
;
Hong-Chang LI
1
;
Qin-Qing LI
2
;
Wen-Jing ZHOU
3
;
Wen-Bin HE
2
;
Jun-Long ZHANG
2
Author Information
1. Shanxi Key Laboratory of Chinese Herbal Medicine Processing,School of Chinese Medicine and Food Engineering,Shanxi University of Chinese Medicine Jinzhong 030619,China.
2. Shanxi Key Laboratory of Chinese Medicine Encephalopathy,Shanxi University of Chinese Medicine Jinzhong 030619,China.
3. School of Basic Medicine,Shanxi University of Chinese Medicine Jinzhong 030619,China.
- Publication Type:Journal Article
- Keywords:
Liujing Toutong Tablets;
NF-κB;
inflammatory reaction;
ischemic stroke;
nerve injury
- MeSH:
Rats;
Male;
Animals;
NF-kappa B/metabolism*;
NF-KappaB Inhibitor alpha/metabolism*;
Vascular Endothelial Growth Factor A/genetics*;
I-kappa B Kinase/pharmacology*;
Tumor Necrosis Factor-alpha/pharmacology*;
Interleukin-6/genetics*;
Calcitonin Gene-Related Peptide/pharmacology*;
Rats, Sprague-Dawley;
Signal Transduction;
Brain Ischemia/drug therapy*;
Tablets
- From:
China Journal of Chinese Materia Medica
2023;48(21):5871-5880
- CountryChina
- Language:Chinese
-
Abstract:
This study investigated the neuroprotective effects and underlying mechanism of Liujing Toutong Tablets(LJTT) on a rat model of permanent middle cerebral artery occlusion(pMCAO). The pMCAO model was established using the suture method. Eighty-four male SPF-grade SD rats were randomly divided into a sham operation group, a model group, a nimodipine group(0.020 g·kg~(-1)), and high-, medium-, and low-dose LJTT groups(2.8, 1.4, and 0.7 g·kg~(-1)). The Longa score, adhesive removal test and laser speckle contrast imaging technique were used to evaluate the degree of neurological functional impairment and changes in local cerebral blood flow. The survival and mortality of rats in each group were recorded daily. After seven days of continuous administration following the model induction, the rats in each group were euthanized, and brain tissue and blood samples were collected for corresponding parameter measurements. Nissl staining was used to examine pathological changes in brain tissue neurons. The levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), IL-1β, vascular endothelial growth factor(VEGF), calcitonin gene-related peptide(CGRP), beta-endorphin(β-EP), and endogenous nitric oxide(NO) in rat serum were measured using specific assay kits. The entropy weight method was used to analyze the weights of various indicators. The protein expression levels of nuclear factor kappa-B(NF-κB), inhibitor kappaB alpha(IκBα), phosphorylated IκBα(p-IκBα), and phosphorylated inhibitor of NF-κB kinase alpha(p-IKKα) in brain tissue were determined using Western blot. Immunohistochemistry was used to detect the protein expression of chemokine-like factor 1(CKLF1) and C-C chemokine receptor 5(CCR5) in rat brain tissue. Compared with the sham operation group, the model group showed significantly higher neurological functional impairment scores, prolonged adhesive removal time, decreased cerebral blood flow, increased neuronal damage, reduced survival rate, significantly increased levels of TNF-α, IL-1β, IL-6, CGRP, and NO in serum, significantly decreased levels of VEGF and β-EP, significantly increased expression levels of NF-κB p65, p-IκBα/IκBα, and p-IKKα in rat brain tissue, and significantly upregulated protein expression of CKLF1 and CCR5. Compared with the model group, the high-dose LJTT group significantly improved the neurological functional score of pMCAO rats after oral administration for 7 days. LJTT at all doses significantly reduced adhesive removal time and restored cerebral blood flow. The high-and medium-dose LJTT groups significantly improved neuronal damage. The LJTT groups at all doses showed reduced levels of TNF-α, IL-1β, IL-6, CGRP, and NO in rat serum, increased VEGF and β-EP levels, and significantly decreased expression levels of NF-κB p65, p-IκBα/IκBα, p-IKKα, and CCR5 protein in rat brain tissue. The entropy weight analysis revealed that CGRP and β-EP were significantly affected during the model induction, and LJTT exhibited a strong effect in reducing the release of inflammatory factors such as TNF-α and IL-1β. LJTT may exert a neuroprotective effect on rats with permanent cerebral ischemia by reducing neuroinflammatory damage, and its mechanism may be related to the inhibition of the NF-κB signaling pathway and the regulation of the CKLF1/CCR5 axis. Additionally, LJTT may exert certain analgesic effects by reducing CGRP and NO levels and increasing β-EP levels.
