Neuroprotective effect of paeonol against isoflurane-induced neuroapoptosis and cognitive dysfunction

Purpose: To investigate whether paeonol affords neuroprotection against isoflurane-induced neurotoxicity.
Methods: Separate groups of neonatal rat pups were administered paeonol (20, 40 or 80 mg/kg) from post-natal day 3 (P3) to post-natal day 15. On post-natal day 7, the pups were exposed to 6 h of isoflurane (0.75 %) anesthesia. TUNEL assay was performed to assess neuroapoptosis. Cleaved caspase-3 expressions were evaluated by immunohistochemistry and western blotting analysis. The expressions of apoptotic pathway proteins and mitogen activated protein kinases (MAPKs) were assessed by western blotting. The general behaviour of the rats was determined by open field test and elevated maze test. Y-maze test and Morris water maze tests were performed to evaluate working memory and cognition.
Results: Isoflurane exposure caused (p < 0.05) severe neuronal apoptosis in the hippocampal region and enhanced caspase-3 expressions. Paeonol supplementation remarkably (p < 0.05) reduced neuronal apoptosis and modulated expressions of apoptotic proteins. The raised expressions of NF-κB, TNF-α, IL-6 and IL-1β and significantly (p < 0.05) enhanced JNK/p38 signalling cascades were inhibited by paeonol. The expression levels of ERK were not significantly (p < 0.05) changed, but there was significant improvement in the general behaviour and working memory of the rats.
Conclusion: Paeonol significantly improves cognitive impairments and offers neuroprotection against isoflurane-induced apoptosis via modulating JNK/ERK/p38 MAPK and NF-κB signaling pathways.

Keywords
Apoptosis; Isoflurane; Neurodegeneration; Paeonol; Cognitive impairment; Signaling pathways