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Chikusetsu saponin IVa alleviated sevoflurane-induced neuroinflammation and cognitive impairment by blocking NLRP3/caspase-1 pathway

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Abstract

Background

Neuroinflammation plays a dominant role in the progression of postoperative cognitive dysfunction (POCD). This study was carried out to explore the neuroprotective effect of Chikusetsu saponin IVa (ChIV) against sevoflurane-induced neuroinflammation and cognitive impairment.

Methods

The neuroprotective activity of ChIV against sevoflurane-induced cognitive dysfunction in aged rats was evaluated by Morris water maze, NOR test and Y-maze test, respectively. The expression of NLRP3, ASC and caspase-1, pro-inflammatory cytokines and apoptotic-related protein were detected in the hippocampus and primary neurons using western blot. TUNEL assay and immunohistochemistry staining were applied to assess the apoptotic cell and number of NLRP3-positive cells in the hippocampus. The oxiSelectIn Vitro ROS/RNS assay kit was used to detect the ROS level. The CCK-8 assay was applied to measure the viability of primary neurons. Flow cytometry was carried out to determine cell apoptosis.

Results

Pretreatment with ChIV significantly alleviated neurological dysfunction in aged rat exposure to sevoflurane. Mechanistically, ChIV treatment significantly alleviated sevoflurane-induced apoptotic cell and neuroinflammation. Of note, the neuroprotective effect of ChIV against sevoflurane-induced neurotoxicity through blocking NLRP3/caspase-1 pathway. In consistent with in vivo studies, ChIV was also able to repress sevoflurane-induced apoptosis and neuroinflammation in primary neurons. Furthermore, pretreatment with NLRP3/caspase-1 pathway inhibitor (MCC950) significantly augmented the neuroprotective effect of ChIV.

Conclusion

Our finding confirmed that ChIV provides a neuroprotective effect against sevoflurane-induced neuroinflammation and cognitive impairment by blocking the NLRP3/caspase-1 pathway, which may be an effective strategy for the clinical treatment of elderly patients with POCD induced by anesthesia.

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The study is supported by funding from hospital to young physicians.

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  1. Department of Anesthesiology, Kunshan Traditional Chinese Medicine Hospital, Chaoyang Road 189, Kunshan, 510530, Jiangsu, China

    Anmin Shao, Jianping Fei, Shuquan Feng & Jiandong Weng

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  1. Anmin Shao
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AS: designed the study, performed the experiments and wrote the paper. JF and SF: performed the experiments and collected the data. JW: analyzed the data.

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Shao, A., Fei, J., Feng, S. et al. Chikusetsu saponin IVa alleviated sevoflurane-induced neuroinflammation and cognitive impairment by blocking NLRP3/caspase-1 pathway. Pharmacol. Rep 72, 833–845 (2020). https://doi.org/10.1007/s43440-020-00078-2

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