Biochanin A protects against angiotensin II-induced damage of dopaminergic neurons in rats associated with the increased endophilin A2 expression.
Behav Pharmacol
; 30(8): 700-711, 2019 12.
Article
em En
| MEDLINE
| ID: mdl-31703032
ABSTRACT
The brain renin-angiotensin system plays a vital role in the modulation of the neuroinflammatory responses and the progression of dopaminergic (DA) degeneration. Angiotensin II (Ang II) induces microglia activation via angiotensin II type 1 receptor (AT1R), which in turn affects the function of DA neurons. Endophilin A2 (EPA2) is involved in fast endophilin-mediated endocytosis and quickly endocytoses several G-protein-coupled receptor (GPCR), while AT1R belongs to GPCR family. Therefore, we speculated that EPA2 may modulate microglia activation via endocytosing AT1R. Biochanin A is an O-methylated isoflavone, classified as a kind of phytoestrogen due to its chemical structure that is similar to mammalian estrogens. In this study, we investigated the protective effects of biochanin A on Ang II-induced DA neurons damage in vivo, and molecular mechanisms. The results showed that biochanin A treatment for 7 days attenuated the behavioral dysfunction, inhibited the microglial activation, and prevented DA neuron damage in Ang II-induced rats. Furthermore, biochanin A increased EPA2 expression and decreased the expression of AT1R, gp91phox, p22 phox, NLRP3, ASC, Caspase-1, IL-1ß, IL-6, IL-18, and TNF-α. In summary, these results suggest that biochanin A exerts protective effects in Ang II-induced model rats, and the mechanisms may involve inhibition of inflammatory responses, an increase in EPA2 expression and a decrease in AT1R expression.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Aciltransferases
/
Genisteína
/
Neurônios Dopaminérgicos
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Behav Pharmacol
Assunto da revista:
CIENCIAS DO COMPORTAMENTO
/
FARMACOLOGIA
Ano de publicação:
2019
Tipo de documento:
Article