Combination of puerarin and tanshinone IIA alleviates ischaemic stroke injury in rats via activating the Nrf2/ARE signalling pathway.
Pharm Biol
; 60(1): 1022-1031, 2022 Dec.
Article
em En
| MEDLINE
| ID: mdl-35635784
ABSTRACT
CONTEXT Puerarin (Pue) and tanshinone IIA (Tan IIA) are often used in combination in the treatment of cerebrovascular diseases. OBJECTIVE:
To investigate the neuroprotective effect and synergic mechanism of Pue-Tan IIA on the treatment of ischaemic stroke (IS). MATERIALS ANDMETHODS:
IS was induced in rats by middle cerebral artery occlusion (MCAO). Rats were intraperitoneally injected with Pue (36 mg/kg), Tan IIA (7.2 mg/kg), or Pue-Tan IIA (36 and 7.2 mg/kg) for five times [30 min before ischaemia, immediately after reperfusion (0 h), 24, 48, and 72 h after reperfusion]. After administration, neurological function assessment and histological changes in the brain were performed. S-100ß and NSE levels were measured to determine the severity of brain injury. Oxidative stress parameters and inflammatory mediators were measured. The proteins involved in Nrf2/ARE signalling pathway were determined by qRT-PCR and western blot.RESULTS:
After administration, the neurological function scores, infarct volume, S-100ß, and NSE levels were significantly reduced in MCAO rats, especially with Pue-Tan IIA treatment (p < 0.05). All treatments increased T-AOC, CAT, SOD, and GSH activities and reduced GSSG activity and MDA, TNF-α, IL-6, ICAM-1, and COX-2 levels in MCAO rats. Pue-Tan IIA significantly increased Nrf2 expression in the nucleus (1.81-fold) and decreased its expression in the cytoplasm (0.60-fold). Pue-Tan IIA significantly increased the expressions of HO-1 (1.87-fold) and NQO1 (1.76-fold) and decreased Keap1 expression (0.39-fold). DISCUSSION ANDCONCLUSIONS:
The combination of Pue and Tan IIA could alleviate ischaemic brain injury by activating Nrf2/ARE signalling pathway, providing an experimental basis for clinical applications.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Lesões Encefálicas
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Isquemia Encefálica
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Abietanos
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AVC Isquêmico
/
Isoflavonas
Limite:
Animals
Idioma:
En
Revista:
Pharm Biol
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China