Quercetin attenuated ropivacaine-induced neurotoxicity in SH-SY5Y cells through upregulating Pim1 and enhancing autophagy

Abstract

Background: Ropivacaine (Rop) is a local anesthetic that is widely used but is also potentially harmful. Quercetin (Quer) is a flavonoid component found in many plants and traditional Chinese medicines. It possesses anti-oxidant, anti-inflammatory, antitumor, and neuroprotective properties as a pharmaceutical. In Rop-induced neurotoxicity, the functions and molecular basis of Quer remain unclear. Methods: Cell viability and proliferation were assessed using CCK-8 and 5-ethynyl-2′-deoxyuridine (EdU) incorporation assays, respectively. Apoptosis and autophagy were defined by both morphological criteria and markers such as caspase3 cleavage and monodansylcadaverine (MDC) staining. Western blot and immunofluorescence staining were evaluated. The target proteins were then predicted using molecular docking and validated at the cellular and protein levels. Results: Quer was shown to significantly reduce Rop-induced viability inhibition and apoptosis in SH-SY5Y cells in a dose-dependent manner. Moreover, Quer reduced Rop-induced cytotoxicity by stimulating autophagy in SH-SY5Y cells by targeting the Pim1 protein, which was accomplished via the AMPK/mTOR pathway. Conclusion: Quer relieved Rop-induced neurotoxicity in SH-SY5Y cells through upregulating Pim1 and enhancing autophagy, indicating that Quer may have potential therapeutic applications in the treatment of Rop-induced neurotoxicities.

Keywords

• Quercetin
• Ropivacaine
• AMPK
• Pim1
• Autophagy