Tetramethylpyrazine inhibits the inflammatory response by downregulating the TNFR1/IκB-α/NF-κB p65 pathway after spinal cord injury
Copyright © 2024. Published by Elsevier Inc..
Previous studies have demonstrated that tetramethylpyrazine (TMP) can enhance the recovery of motor function in spinal cord injury (SCI) rats. However, the underlying mechanism involved in this therapeutic effect remains to be elucidated. We conducted RNA sequencing with a network pharmacology strategy to predict the targets and mechanism of TMP for SCI. The modified Allen's weight-drop method was used to construct an SCI rat model. The results indicated that the nuclear transfer factor-κB (NF-κB) pathway was identified through the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and an inflammatory response was identified through the Gene Ontology (GO) enrichment analysis. Tumor necrosis factor (TNF) was identified as a crucial target. Western blotting revealed that TMP decreased the protein expression of TNF superfamily receptor 1 (TNFR1), inhibitor κB-α (IκB-α), and NF-κB p65 in spinal cord tissues. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) demonstrated that TMP inhibited TNF-α, interleukin-1β (IL-1β), reactive oxygen species (ROS), and malondialdehyde (MDA) expression and enhanced superoxide dismutase (SOD) expression. Histopathological observation and behavior assessments showed that TMP improved morphology and motor function. In conclusion, TMP inhibits inflammatory response and oxidative stress, thereby exerting a neuroprotective effect that may be related to the regulation of the TNFR1/IκB-α/NF-κB p65 signaling pathway.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:484 |
|---|---|
| Enthalten in: |
Toxicology and applied pharmacology - 484(2024) vom: 29. März, Seite 116872 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Liu, Gang [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 20.03.2024 Date Revised 20.03.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.taap.2024.116872 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM36918341X |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM36918341X | ||
| 003 | DE-627 | ||
| 005 | 20240320234451.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240302s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.taap.2024.116872 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1337.xml |
| 035 | |a (DE-627)NLM36918341X | ||
| 035 | |a (NLM)38428465 | ||
| 035 | |a (PII)S0041-008X(24)00070-X | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Liu, Gang |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Tetramethylpyrazine inhibits the inflammatory response by downregulating the TNFR1/IκB-α/NF-κB p65 pathway after spinal cord injury |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 20.03.2024 | ||
| 500 | |a Date Revised 20.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2024. Published by Elsevier Inc. | ||
| 520 | |a Previous studies have demonstrated that tetramethylpyrazine (TMP) can enhance the recovery of motor function in spinal cord injury (SCI) rats. However, the underlying mechanism involved in this therapeutic effect remains to be elucidated. We conducted RNA sequencing with a network pharmacology strategy to predict the targets and mechanism of TMP for SCI. The modified Allen's weight-drop method was used to construct an SCI rat model. The results indicated that the nuclear transfer factor-κB (NF-κB) pathway was identified through the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and an inflammatory response was identified through the Gene Ontology (GO) enrichment analysis. Tumor necrosis factor (TNF) was identified as a crucial target. Western blotting revealed that TMP decreased the protein expression of TNF superfamily receptor 1 (TNFR1), inhibitor κB-α (IκB-α), and NF-κB p65 in spinal cord tissues. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) demonstrated that TMP inhibited TNF-α, interleukin-1β (IL-1β), reactive oxygen species (ROS), and malondialdehyde (MDA) expression and enhanced superoxide dismutase (SOD) expression. Histopathological observation and behavior assessments showed that TMP improved morphology and motor function. In conclusion, TMP inhibits inflammatory response and oxidative stress, thereby exerting a neuroprotective effect that may be related to the regulation of the TNFR1/IκB-α/NF-κB p65 signaling pathway | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Inflammatory response | |
| 650 | 4 | |a NF-κB signaling pathway | |
| 650 | 4 | |a Network pharmacology | |
| 650 | 4 | |a RNA-seq | |
| 650 | 4 | |a Spinal cord injury | |
| 650 | 4 | |a Tetramethylpyrazine | |
| 650 | 7 | |a NF-kappa B |2 NLM | |
| 650 | 7 | |a NF-KappaB Inhibitor alpha |2 NLM | |
| 650 | 7 | |a 139874-52-5 |2 NLM | |
| 650 | 7 | |a Pyrazines |2 NLM | |
| 650 | 7 | |a Receptors, Tumor Necrosis Factor, Type I |2 NLM | |
| 650 | 7 | |a tetramethylpyrazine |2 NLM | |
| 650 | 7 | |a V80F4IA5XG |2 NLM | |
| 650 | 7 | |a Tumor Necrosis Factor-alpha |2 NLM | |
| 700 | 1 | |a Huo, Luyao |e verfasserin |4 aut | |
| 700 | 1 | |a Deng, Bowen |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Shengyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Yi |e verfasserin |4 aut | |
| 700 | 1 | |a Mo, Yanjun |e verfasserin |4 aut | |
| 700 | 1 | |a Bai, Huizhong |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Lin |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Chuanyu |e verfasserin |4 aut | |
| 700 | 1 | |a Mu, Xiaohong |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Toxicology and applied pharmacology |d 1959 |g 484(2024) vom: 29. März, Seite 116872 |w (DE-627)NLM000010979 |x 1096-0333 |7 nnns |
| 773 | 1 | 8 | |g volume:484 |g year:2024 |g day:29 |g month:03 |g pages:116872 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.taap.2024.116872 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 484 |j 2024 |b 29 |c 03 |h 116872 | ||