Clematichinenoside AR improves isoflurane-stimulated cognitive dysfunction in aged mice by ameliorating neurotoxicity through ERK-CREB pathway

Background: Postoperative cognitive dysfunction (POCD) can result in decreased memory and information processing speed after anesthesia. Clematichinenoside AR (AR) has recently been recognized for its multiple biological activities, including anti-inflammatory and anti-apoptotic properties. However, its effectiveness in alleviating symptoms of POCD is not yet well understood. Our objective is to evaluate and explore the role of AR in addressing POCD. Methods: Mice were divided into 5 groups: sham, isoflurane, isoflurane + AR (8 mg/kg), isoflurane + AR (16 mg/kg) and isoflurane + AR (32 mg/kg). The Morris Water Maze (MWM) test and Fear Conditioning Test (FCT) were conducted to evaluate the role of AR in mice with POCD. Subsequently, Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and Immunoblotting were performed to confirm the effects of AR on cell apoptosis. Furthermore, Quantitative Polymerase Chain Reaction (qPCR) and Enzyme-Linked Immunosorbent Assay (ELISA) were utilized to verify the impact of AR on inflammation. The morphology of hippocampal neurons and protein expression were examined through Hematoxylin and Eosin (H&E) staining and western blot. Results: The results indicated that AR can enhance isoflurane-stimulated cognitive dysfunction in mice. In addition, AR exhibits anti-apoptotic and anti-inflammatory effects in POCD mice, highlighting its neuroprotective effects. Additionally, AR activates the Extracellular Signal-Regulated Kinase—cAMP Response Element-Binding Protein (ERK-CREB) signaling pathway. Conclusions: AR improves isoflurane-stimulated cognitive dysfunction in aged mice by ameliorating neurotoxicity.

Clematichinenoside AR; Postoperative cognitive dysfunction (POCD); Isoflurane; ERK; CREB

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