期刊
BEHAVIOURAL PHARMACOLOGY
卷 30, 期 8, 页码 699-710出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/FBP.0000000000000515
关键词
angiotensin II; biochanin A; endophilin A2; NADPH; NLRP3; rat
资金
- Natural Science Foundation of Anhui Province Education Department [KJ2018A171]
- Natural Science Foundation of Anhui Province [1508085MH186, 1908085MH270]
- National Undergraduate training Program for Innovation and Entrepreneurship [201810366021]
- National Natural Science Foundation of China [31171650]
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-1 beta, IL-6, IL-18, and TNF-alpha. 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.
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