2. Academic Validation
  3. Oridonin prevents insulin resistance-mediated cognitive disorder through PTEN/Akt pathway and autophagy in minimal hepatic encephalopathy

Oridonin prevents insulin resistance-mediated cognitive disorder through PTEN/Akt pathway and autophagy in minimal hepatic encephalopathy

  • J Cell Mol Med. 2020 Jan;24(1):61-78. doi: 10.1111/jcmm.14546.
Fangfang Wen 1 2,  Weishan Zhuge 3,  Jian Wang 1 2,  Xiaoai Lu 1,  Ruimin You 1,  Leping Liu 1,  Qichuan Zhuge 4,  Saidan Ding 1
Affiliations

Affiliations

  • 1 Zhejiang Provincial Key Laboratory of Aging and Neurological Disease Research, Department of Surgery Laboratory, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
  • 2 Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
  • 3 Gastrointestinal Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
  • 4 Neurosurgery Department, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
PMID: 31568638 DOI: 10.1111/jcmm.14546
Abstract

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.

Keywords

autophagy; cognitive; insulin resistance; minimal hepatic encephalopathy; oridonin; synaptic.

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