{"title":"Network pharmacology analysis and experimental validation to explore the effect and mechanism of tetramethylpyrazine for spinal cord injury","authors":"Guodong Qi , Shujun Li , Qiong Jiang , Zhijuan Yu , Zhenggang Peng , Qiurui Li , Wei Qi , Mingjun Guo","doi":"10.1016/j.jchemneu.2023.102386","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><p>To investigate the effect and mechanism of Tetramethylpyrazine (TMP) in treating Spinal Cord Injury (SCI) using network pharmacology analysis and animal experiments.</p></div><div><h3>Methods</h3><p>This study was based on public databases, including PharmMapper, BATMAN-TCM, and STRING, as well as KEGG pathway analysis and other methods of network pharmacology were used to preliminarily explore the molecular mechanism of TMP in the treatment of SCI. Using a mouse SCI compression injury model, the efficacy of TMP was evaluated, and the expression of predictive targets on the PI3K/AKT and MAPK signaling pathways was measured using Western blotting and q-PCR.</p></div><div><h3>Results</h3><p>Network pharmacology analysis showed that TMP may exert therapeutic effects through the MAPK and PI3K/AKT signaling pathways. In animal experimental validation studies, it was shown that after treatment with TMP, the hind limb motor function scores and ramp test scores of the TMP-treated mice improved significantly. HE staining showed that after treatment with TMP, cavities decreased, fewer glial cells proliferated, and fewer inflammatory cells infiltrated; Nielsen staining showed less neuronal loss. Western blot studies showed that compared with the model group, expression of RAS, ERK1/2, RAF1, PI3K, and p-AKT proteins in the spinal cord tissue of mice treated with high-dose TMP was significantly lower. Accordingly, q-PCR studies showed that compared with the model group, the expression levels of RAS, ERK1/2, RAF1, PI3K, and p-AKT genes in the spinal cords of mice in the high-dose TMP group were significantly lower.</p></div><div><h3>Conclusion</h3><p>TMP exhibits a good neuroprotective effect after SCI, which may be related to inhibition of the MAPK and PI3K/AKT signaling pathways.</p></div>","PeriodicalId":15324,"journal":{"name":"Journal of chemical neuroanatomy","volume":"136 ","pages":"Article 102386"},"PeriodicalIF":2.7000,"publicationDate":"2024-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0891061823001564/pdfft?md5=5e789d7d872016a7290b434fbf53fb5e&pid=1-s2.0-S0891061823001564-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of chemical neuroanatomy","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0891061823001564","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Objective
To investigate the effect and mechanism of Tetramethylpyrazine (TMP) in treating Spinal Cord Injury (SCI) using network pharmacology analysis and animal experiments.
Methods
This study was based on public databases, including PharmMapper, BATMAN-TCM, and STRING, as well as KEGG pathway analysis and other methods of network pharmacology were used to preliminarily explore the molecular mechanism of TMP in the treatment of SCI. Using a mouse SCI compression injury model, the efficacy of TMP was evaluated, and the expression of predictive targets on the PI3K/AKT and MAPK signaling pathways was measured using Western blotting and q-PCR.
Results
Network pharmacology analysis showed that TMP may exert therapeutic effects through the MAPK and PI3K/AKT signaling pathways. In animal experimental validation studies, it was shown that after treatment with TMP, the hind limb motor function scores and ramp test scores of the TMP-treated mice improved significantly. HE staining showed that after treatment with TMP, cavities decreased, fewer glial cells proliferated, and fewer inflammatory cells infiltrated; Nielsen staining showed less neuronal loss. Western blot studies showed that compared with the model group, expression of RAS, ERK1/2, RAF1, PI3K, and p-AKT proteins in the spinal cord tissue of mice treated with high-dose TMP was significantly lower. Accordingly, q-PCR studies showed that compared with the model group, the expression levels of RAS, ERK1/2, RAF1, PI3K, and p-AKT genes in the spinal cords of mice in the high-dose TMP group were significantly lower.
Conclusion
TMP exhibits a good neuroprotective effect after SCI, which may be related to inhibition of the MAPK and PI3K/AKT signaling pathways.
期刊介绍：
The Journal of Chemical Neuroanatomy publishes scientific reports relating the functional and biochemical aspects of the nervous system with its microanatomical organization. The scope of the journal concentrates on reports which combine microanatomical, biochemical, pharmacological and behavioural approaches.
Papers should offer original data correlating the morphology of the nervous system (the brain and spinal cord in particular) with its biochemistry. The Journal of Chemical Neuroanatomy is particularly interested in publishing important studies performed with up-to-date methodology utilizing sensitive chemical microassays, hybridoma technology, immunocytochemistry, in situ hybridization and receptor radioautography, to name a few examples.
The Journal of Chemical Neuroanatomy is the natural vehicle for integrated studies utilizing these approaches. The articles will be selected by the editorial board and invited reviewers on the basis of their excellence and potential contribution to this field of neurosciences. Both in vivo and in vitro integrated studies in chemical neuroanatomy are appropriate subjects of interest to the journal. These studies should relate only to vertebrate species with particular emphasis on the mammalian and primate nervous systems.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
