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Tytuł:
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Chikusetsu saponin IVa alleviated sevoflurane-induced neuroinflammation and cognitive impairment by blocking NLRP3/caspase-1 pathway.
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Autorzy:
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Shao A; Department of Anesthesiology, Kunshan Traditional Chinese Medicine Hospital, Chaoyang Road 189, Kunshan, 510530, Jiangsu, China. .
Fei J; Department of Anesthesiology, Kunshan Traditional Chinese Medicine Hospital, Chaoyang Road 189, Kunshan, 510530, Jiangsu, China.
Feng S; Department of Anesthesiology, Kunshan Traditional Chinese Medicine Hospital, Chaoyang Road 189, Kunshan, 510530, Jiangsu, China.
Weng J; Department of Anesthesiology, Kunshan Traditional Chinese Medicine Hospital, Chaoyang Road 189, Kunshan, 510530, Jiangsu, China.
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Źródło:
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Pharmacological reports : PR [Pharmacol Rep] 2020 Aug; Vol. 72 (4), pp. 833-845. Date of Electronic Publication: 2020 Mar 02.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Publication: 2020- : Cham, Switzerland : Springer International Publishing
Original Publication: Kraków, Poland : Institute of Pharmacology, Polish Academy of Sciences, c2005-
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MeSH Terms:
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Caspase Inhibitors/*therapeutic use
Cognitive Dysfunction/*drug therapy
Inflammation Mediators/*antagonists & inhibitors
NLR Family, Pyrin Domain-Containing 3 Protein/*antagonists & inhibitors
Oleanolic Acid/*analogs & derivatives
Saponins/*therapeutic use
Sevoflurane/*toxicity
Anesthetics, Inhalation/toxicity ; Animals ; Caspase 1/metabolism ; Caspase Inhibitors/pharmacology ; Cognitive Dysfunction/chemically induced ; Cognitive Dysfunction/metabolism ; Hippocampus/drug effects ; Hippocampus/metabolism ; Inflammation Mediators/metabolism ; Male ; Maze Learning/drug effects ; Maze Learning/physiology ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Oleanolic Acid/pharmacology ; Oleanolic Acid/therapeutic use ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Saponins/pharmacology
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Contributed Indexing:
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Keywords: Chikusetsu saponin IVa; NLRP3 inflammasome; Neuroinflammation; Sevoflurane
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Substance Nomenclature:
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0 (Anesthetics, Inhalation)
0 (Caspase Inhibitors)
0 (Inflammation Mediators)
0 (NLR Family, Pyrin Domain-Containing 3 Protein)
0 (Nlrp3 protein, rat)
0 (Saponins)
38LVP0K73A (Sevoflurane)
51415-02-2 (chikusetsu saponin IVa)
6SMK8R7TGJ (Oleanolic Acid)
EC 3.4.22.36 (Caspase 1)
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Entry Date(s):
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Date Created: 20200304 Date Completed: 20210528 Latest Revision: 20210528
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Update Code:
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20240105
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DOI:
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10.1007/s43440-020-00078-2
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PMID:
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32124392
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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.
