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-1β, 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.
aDepartment of Pharmacology, Anhui Medical University
bSchool of Food and Biological Engineering, Hefei University of Technology, Hefei, Anhui, People’s Republic of China
* Hai-Xia Xue and Hua Kong contributed equally to the writing of this article.
Received 2 August 2019 Accepted as revised 30 September 2019
Correspondence to Yan-Yan Yin, PhD, Professor, Department of Pharmacology, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, People’s Republic of China, E-mail: email@example.com
Corresponding Author: Han-Qing Chen, Ph.D./Professor, School of Food and Biological Engineering, Hefei University of Technology. E-mail: firstname.lastname@example.org (H.-Q. Chen).