Cucurbitacin E reduces the cognitive dysfunction induced by sevoflurane in rats by regulating NF-κB pathway.

Abstract

Perioperative neurocognitive disorders (PND) occur frequently and refer to alterations in cognitive function after surgery, especially in elderly patients. PND is characterized as abnormalities of learning, memory, language, and emotions. Cucurbitacin E has been reported to possess various pharmacological properties, including anticancer, antiviral, and anti-inflammatory effects. In this study, we investigated whether cucurbitacin E could alleviate sevoflurane-induced cognitive dysfunction in rats. Sprague-Dawley male rats (~6 weeks old) were randomly assigned to three groups: the control group, the Sevoflurane group, and the Sevoflurane + Cucurbitacin E group. Subsequently, the cognitive dysfunction of the rats was evaluated through the morris water maze test. Hematoxylin and eosin (HE) staining was used to measure the pathological change in brain tissues. Enzyme-linked immunosorbent assay (ELISA) kits were used for determinations of S-100 calcium binding protein B (S-100β) and neuron-specific enolase (NSE) and cytokine. Cell apoptosis was analyzed by TdT-Mediated Nick-End Labeling (TUNEL) staining. Protein levels were confirmed by Western blotting. Cucurbitacin E relieved brain injury in rats induced by sevoflurane. Cucurbitacin E alleviated sevoflurane-induced S-100β and NSE levels. Additionally, the Morris water maze task revealed that cucurbitacin E attenuated cognition impairment in sevoflurane-induced rats. Sevoflurane increased levels of IL-6, TNF-α and IL-1β levels, and decreased the level of IL-10. However, cucurbitacin E exhibited opposite effects on these cytokines, which were induced by sevoflurane. Furthermore, cucurbitacin E inhibited sevoflurane-induced neuron apoptosis and NF-κB pathway in rats. These findings indicate that cucurbitacin E can improve sevoflurane-induced cognitive dysfunction in rats by regulating NF-κB pathway, which provided a new strategy for PND treatment.