Open AccessOridonin prevents insulin resistance–mediated cognitive disorder through PTEN/Akt pathway and autophagy in minimal hepatic encephalopathy
Author(s) -
Wen Fangfang,
Zhuge Weishan,
Wang Jian,
Lu Xiaoai,
You Ruimin,
Liu Leping,
Zhuge Qichuan,
Ding Saidan
Publication year - 2020
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14546
Subject(s) - pten , insulin resistance , autophagy , pi3k/akt/mtor pathway , protein kinase b , hepatic encephalopathy , insulin , cancer research , insulin receptor , medicine , endocrinology , biology , pharmacology , chemistry , phosphorylation , signal transduction , microbiology and biotechnology , biochemistry , apoptosis , cirrhosis
Minimal hepatic encephalopathy (MHE) was characterized for cognitive dysfunction. Insulin resistance (IR) has been identified to be correlated with the pathogenesis of MHE. Oridonin (Ori) is an active terpenoid, which has been reported to rescue synaptic loss and restore insulin sensitivity. In this study, we found that intraperitoneal injection of Ori rescued IR, reduced the autophagosome formation and synaptic loss and improved cognitive dysfunction in MHE rats. Moreover, in insulin‐resistant PC12 cells and N2a cells, we found that Ori blocked IR‐induced synaptic deficits via the down‐regulation of PTEN, the phosphorylation of Akt and the inhibition of autophagy. Taken together, these results suggested that Ori displays therapeutic efficacy towards memory deficits via improvement of IR in MHE and represents a novel bioactive therapeutic agent for treating MHE.