Isofraxidin ameliorated influenza viral inflammation in rodents via inhibiting platelet aggregation.
Int Immunopharmacol
; 84: 106521, 2020 Jul.
Article
em En
| MEDLINE
| ID: mdl-32315950
ABSTRACT
Platelets have been proved to exacerbate influenza infection and its complications. Inhibition of platelet activation may be a feasible method for preventing severe infection and secondary acute lung injury (ALI). Isofraxidin (IFD) is a natural coumarin isolated from the plants Sarcandra glabra and Siberian ginseng, and exerts anticancer, antioxidant and antiinflammatory effects. In the present study, we examined the therapeutic effects of IFD in ADP- or arachidonic acid (AA)-induced platelet aggregation model and in influenza A virus (IAV)-induced ALI mouse model. The results showed that IFD significantly inhibited platelet aggregation induced by ADP and AA in vitro in a concentration-dependent manner as well as the release of soluble P-selectin and platelet factor 4. Moreover, IFD significantly relieved IAV-induced lung inflammation, reduced the expressions of platelet activation biomarkers (P-selectin and CD61), decreased the serum levels of TNF-α, IL-1ß, IL-6 and MIP-2, suppressed peripheral platelet aggregation and prolonged the survival time of infected mice. The western blotting results also demonstrated that IFD reduced the phosphorylation levels of PI3K, AKT and p38 in the activated platelets stimulated by ADP and IAV infection. But IFD did not have any effects on IAV replication. It indicated that IFD ameliorated IAV-induced severe lung damage and lethal infection by suppressing platelet aggregation via regulating PI3K/AKT and MAPK pathways.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Inibidores da Agregação Plaquetária
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Infecções por Orthomyxoviridae
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Cumarínicos
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Alphainfluenzavirus
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Lesão Pulmonar Aguda
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Anti-Inflamatórios
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article