Open AccessIpriflavone as a non‐steroidal glucocorticoid receptor antagonist ameliorates diabetic cognitive impairment in mice
Author(s) -
Nie Ruifang,
Lu Jian,
Xu Rui,
Yang Juanzhen,
Shen Xingyi,
Ouyang Xingnan,
Zhu Danyang,
Huang Yujie,
Zhao Tong,
Zhao Xuejian,
Lu Yin,
Qian Minyi,
Wang Jiaying,
Shen Xu
Publication year - 2022
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.13572
Subject(s) - antagonist , glucocorticoid receptor , glucocorticoid , creb , endocrinology , neurogenesis , receptor antagonist , medicine , pi3k/akt/mtor pathway , pharmacology , hyperphosphorylation , downregulation and upregulation , biology , receptor , neuroscience , signal transduction , kinase , transcription factor , biochemistry , microbiology and biotechnology , gene
Diabetic cognitive impairment (DCI) is a common diabetic complication with hallmarks of loss of learning ability and disorders of memory and behavior. Glucocorticoid receptor (GR) dysfunction is a main reason for neuronal impairment in brain of diabetic patients. Here, we determined that ipriflavone (IP) a clinical anti‐osteoporosis drug functioned as a non‐steroidal GR antagonist and efficiently ameliorated learning and memory dysfunction in both type 1 and 2 diabetic mice. The underlying mechanism has been intensively investigated by assay against the diabetic mice with GR‐specific knockdown in the brain by injection of adeno‐associated virus (AAV)‐ePHP‐ si ‐ GR . IP suppressed tau hyperphosphorylation through GR/PI3K/AKT/GSK3β pathway, alleviated neuronal inflammation through GR/NF‐κB/NLRP3/ASC/Caspase‐1 pathway, and protected against synaptic impairment through GR/CREB/BDNF pathway. To our knowledge, our work might be the first to expound the detailed mechanism underlying the amelioration of non‐steroidal GR antagonist on DCI‐like pathology in mice and report the potential of IP in treatment of DCI.