Article ; Online: Pien-Tze-Huang
2021 Volume 59, Issue 1, Page(s) 828–839
Abstract: Context: Pien-Tze-Huang: Objective: This study investigates the anti-inflammatory effects and ...
Abstract | Context: Pien-Tze-Huang Objective: This study investigates the anti-inflammatory effects and its underlying mechanism of PTH on ischaemic stroke. Materials and methods: Cerebral ischaemia-reperfusion injury was induced through 2 h middle cerebral artery occlusion (MCAO) followed by 24 h reperfusion in male Sprague-Dawley (SD) rats receiving oral pre-treatment with PTH (180 mg/kg) for 4 days. TLR4 antagonist TAK-242 (3 mg/kg) was injected intraperitoneally at 1.5 h after MCAO. MRI, HE staining, qRT-PCR, western blot, and immunofluorescence methods were employed. Results: PTH treatment markedly reduced cerebral infarct volume (by 51%), improved neurological function (by 33%), and ameliorated brain histopathological damage in MCAO rats. It also reduced the levels of four inflammatory mediators including IL-1β (by 70%), IL-6 (by 78%), TNF-α (by 60%) and MCP-1 (by 58%); inhibited microglia and astrocyte activation; and decreased protein expression of iNOS and COX-2 in injured brains. Moreover, PTH down-regulated the protein expressions of TLR4, MyD88, and TRAF6; reduced the expression and nuclear translocation of NF-κB; and lowered the protein expressions of p-ERK1/2, p-JNK, and p-p38. Similar effects were observed in MCAO rats with TAK-242 treatment. However, combined administration of PTH and TAK-242 did not significantly reinforce the anti-inflammatory effects of PTH. Discussion and conclusion: PTH improved cerebral ischaemia-reperfusion injury by inhibiting neuroinflammation partly via the TLR4/NF-κB/MAPK signalling pathway, which will help guide its clinical application. |
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MeSH term(s) | Animals ; Anti-Inflammatory Agents/pharmacology ; Brain Ischemia/drug therapy ; Brain Ischemia/pathology ; Disease Models, Animal ; Drugs, Chinese Herbal/pharmacology ; Infarction, Middle Cerebral Artery ; Ischemic Stroke/drug therapy ; Ischemic Stroke/pathology ; MAP Kinase Signaling System/drug effects ; Male ; NF-kappa B/metabolism ; Neuroinflammatory Diseases/drug therapy ; Neuroinflammatory Diseases/pathology ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury/complications ; Reperfusion Injury/drug therapy ; Sulfonamides/pharmacology ; Toll-Like Receptor 4/metabolism |
Chemical Substances | Anti-Inflammatory Agents ; Drugs, Chinese Herbal ; NF-kappa B ; Sulfonamides ; Tlr4 protein, rat ; Toll-Like Receptor 4 ; ethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-ene-1-carboxylate ; pien tze huang |
Language | English |
Publishing date | 2021-07-01 |
Publishing country | England |
Document type | Journal Article |
ZDB-ID | 1440131-9 |
ISSN | 1744-5116 ; 1388-0209 |
ISSN (online) | 1744-5116 |
ISSN | 1388-0209 |
DOI | 10.1080/13880209.2021.1942926 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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