Pien-Tze-Huang attenuates neuroinflammation in cerebral ischaemia-reperfusion injury in rats through the TLR4/NF-κB/MAPK pathway.
Pharm Biol
; 59(1): 828-839, 2021 Dec.
Article
in En
| MEDLINE
| ID: mdl-34196587
ABSTRACT
CONTEXT Pien-Tze-Huang (PTH) is traditionally applied to treat various inflammation-related diseases including stroke. However, literature regarding the anti-inflammatory effects and possible mechanisms of PTH in ischaemic stroke is unavailable. OBJECTIVE:
This study investigates the anti-inflammatory effects and its underlying mechanism of PTH on ischaemic stroke. MATERIALS ANDMETHODS:
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-1ß (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 ANDCONCLUSION:
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Drugs, Chinese Herbal
/
Ischemic Stroke
/
Neuroinflammatory Diseases
/
Anti-Inflammatory Agents
Type of study:
Prognostic_studies
/
Qualitative_research
Limits:
Animals
Language:
En
Journal:
Pharm Biol
Year:
2021
Document type:
Article
Affiliation country: