Abstract
Cerebral infarction (CI), a common cerebrovascular disease worldwide, is caused by unknown factors common to many diseases, including hypokalemia, respiratory diseases, and lower extremity venous thrombosis. Tianma Gouteng (TMGT), a traditional Chinese Medicine (TCM) prescription, has been used for the clinical treatment of CI. In this study, high-performance liquid chromatography (HPLC) fingerprint analysis was used to detect and identify major chemical constituents of TMGT. TCMSP and BATMAN-TCM databases were used to screen for active TMGT constituent compounds, while the GeneCards database was used to screen for protein targets associated with CI. Next, GO and KEGG enrichment analysis of these core nodes were performed to determine the identities of key associated biological processes and signal pathways. Meanwhile, a total of six possible gene targets of TMGT, including NFKBIA, PPARG, IL6, IL1B, CXCL8, and HIF1A, were selected for further study using two cellular models of CI. For one model, PC12 cells were treated under oxygen and glucose deprivation (OGD) conditions to generate an OGD cellular model of CI, while for the other model, BV2 cells were stimulated with lipopolysaccharide (LPS) to generate a cellular model of CI-associated inflammation. Ultimately TMGT treatment increased PPARγ expression and downregulated the expression of p-P65, p-IκBα, and HIF-1α in both OGD-induced and LPS-induced cell models of CI. In addition, molecular docking analysis showed that one TMGT chemical constituent, quercetin, may be a bioactive TMGT compound with activity that may be associated with the alleviation of neuronal damage and neuroinflammation triggered by CI. Moreover, additional data obtained in this work revealed that TMGT could inhibit neuroinflammation and protect brain cells from OGD-induced and LPS-induced damage by altering HIF-1α/PPARγ/NF-κB pathway functions. Thus, targeting this pathway through TMGT administration to CI patients may be a strategy for alleviating nerve injury and neuroinflammation triggered by CI.
Highlights
Stroke, a common cerebrovascular disease worldwide with high morbidity and mortality, can seriously impact an individual’s quality of life (Takeda et al, 2021)
Screening of published literature for information regarding Tianma Gouteng (TMGT) active ingredients using the keywords “TianMa” and “GouTeng” led to the identification of a total of 46 active ingredients (Supplementary Table S2). These ingredients were subsequently verified through searches of TCM systems pharmacology (TCMSP) and BATMAN-traditional Chinese medicine (TCM) databases based on the criteria that included oral bioavailability OB ≥30% and drug-like DL ≥0.18
Target genes identified from analysis of interaction networks were input into STRING to generate the protein–protein interaction (PPI) network
Summary
A common cerebrovascular disease worldwide with high morbidity and mortality, can seriously impact an individual’s quality of life (Takeda et al, 2021). Results of statistical analysis of current trends indicate that the incidence of ischemic stroke will remain high in the coming decades (Howard and Goff, 2012). Cerebral infarction (CI) is a state of stroke accompanied by the obstruction of blood flow that leads to the interruption of blood supply to CNS tissues. Various biological processes are involved in the development or progression of CI, including neuroinflammation and ischemia-hypoxic injury. Multiple interventions are used to treat stroke due to the complex pathogenic mechanisms associated with the disorder. Patient outcomes are often unsatisfactory, prompting researchers to find new drugs or treatment strategies to ameliorate CNS damage resulting from CI
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
