Protective effects of grape seed procyanidin on isoflurane-induced cognitive impairment in mice

Abstract

Context: Oxidative imbalance-induced cognitive impairment is among the most urgent clinical concerns. Isoflurane has been demonstrated to impair cognitive function via an increase in oxidative stress. GSP has strong antioxidant capacities, suggesting potential cognitive benefits. Objective: This study investigates whether GSP pre-treatment can alleviate isoflurane-induced cognitive dysfunction in mice. Materials and methods: C57BL/6J mice were pre-treated with either GSP 25-100 mg/kg/d for seven days or GSP 100-400 mg/kg as a single dose before the 6 h isoflurane anaesthesia. Cognitive functioning was examined using the fear conditioning tests. The levels of SOD, p-NR2B and p-CREB in the hippocampus were also analysed. Results: Pre-treatment with either a dose of GSP 50 mg/kg/d for seven days or a single dose of GSP 200 mg/kg significantly increased the % freezing time in contextual tests on the 1st (72.18 ± 12.39% vs. 37.60 ± 8.93%; 78.27 ± 8.46% vs. 52.72 ± 2.64%), 3rd (93.80 ± 7.62% vs. 52.94 ± 14.10%; 87.65 ± 10.86% vs. 52.89 ± 1.73%) and 7th (91.36 ± 5.31% vs. 64.09 ± 14.46%; 93.78 ± 3.92% vs. 79.17 ± 1.79%) day after anaesthesia. In the hippocampus of mice exposed to isoflurane, GSP 200 mg/kg increased the total SOD activity on the 1st and 3rd day and reversed the decreased activity of the NR2B/CREB pathway. Discussion and conclusions: These findings suggest that GSP improves isoflurane-induced cognitive dysfunction by protecting against perturbing antioxidant enzyme activities and NR2B/CREB pathway. Therefore, GSP may possess a potential prophylactic role in isoflurane-induced and other oxidative stressrelated cognitive decline.

Inhibition of the integrated stress response reverses oxidative stress damage-induced postoperative cognitive dysfunction

“…Confounding multi-factorial causes of POCD and oxidative stress are important in the pathogenesis of POCD (Netto et al, 2018 ). Our research group used natural extracts, such as green tea polyphenols (Song et al, 2019 ) and grape seed procyanidin (Gong et al, 2020 ), to alleviate oxidative stress levels in the hippocampus, both of which reversed the cognitive dysfunction induced by long-term isoflurane anesthesia. How to alleviate the level of oxidative stress caused by surgery may be one of the strategies for the treatment of POCD.…”

“…Taken together, our data suggested that surgery induced cognitive impairment, and the impairment could be attenuated by ISRIB. To elucidate the molecular mechanism underlying cognitive impairment, our previous studies showed that two cognitive-related proteins, P-NR2B and BDNF, are damaged in the hippocampus of POCD mice (Song et al, 2019 ; Gong et al, 2020 ). In the current experiments, we also detected these two proteins.…”

“…The mechanisms underlying POCD include oxidative stress damage (Netto et al, 2018 ), neuroinflammation (Luo et al, 2019 ), and blood-brain barrier damage (Zhang et al, 2016 ). Our previous studies showed that oxidative stress plays an important role in the development of POCD (Song et al, 2019 ; Gong et al, 2020 ; Liu et al, 2020 ). Numerous cellular mechanisms associated with oxidative stress damage are involved in the occurrence of various types of neurodegenerative diseases.…”

The Antarctic Moss Pohlia nutans Genome Provides Insights Into the Evolution of Bryophytes and the Adaptation to Extreme Terrestrial Habitats

“…In contrast, anthocyanins were not detected in methanolic extracts of P. patens separated by HPLC method (Wolf et al, 2010). Similarly, several SCMs like procyanidin and luteolin were detected in P. nutans, and functioned as an efficient antioxidant (Gong et al, 2020). Notably, several Antarctic mosses (e.g., Bryum pseudotriquetrum, C. perpureus, and Schistidium antarctici) and liverwort (M. polymorpha) possess anthocyanins, but Antarctic algae do not have anthocyanins (Singh et al, 2011).…”

Natural bioactive compounds in Alzheimer's disease: From the perspective of type 3 diabetes mellitus

“…Notably, PCs and some of their metabolites stimulate CREB, acting as a molecular switch from short- to long-term memory, based on the interplay of the CREB-SIRT1 axis (Zhao et al, 2019 ). Grape seed PCs (GSPCs) improve isoflurane-induced cognitive dysfunction by protecting against perturbing antioxidant enzyme activities and the NR2B/CREB pathway (Gong et al, 2020 ). In addition, the PCs effectively inhibit the aggregation of human islet amyloid polypeptide (hIAPP) and Aβ through hydrophobic and hydrogen bonding interactions and also dissolve the aged fibrils (Xu et al, 2021 ).…”