Urolithin A attenuates bupivacaine-induced neurotoxicity in SH-SY5Y cells by regulating the SIRT1-activated PI3K/AKT pathway

. Urolithin A (UroA) is well-recognized for its anti-oxidative, anti-inflammatory, and immunomodulatory potentials and has been proven to have neuroprotective effects. Nevertheless, the potential of UroA on bupivacaine (BUP)-induced neurotoxicity has never been reported. Using SH-SY5Y cells to establish a cell model, it was revealed that BUP stimulated cell viability reduction, LDH release increase, and SH-SY5Y cells, whereas UroA treatment caused an effective abrogation of the effects of BUP. Besides, SIRT1 overexpression caused an enhancement in the activity of PI3K/AKT signaling in BUP and UroA cotreated cells, indicating that SIRT1 mediated the activity induced apoptosis, oxidative stress, and inflammatory responses in SH-SY5Y cells. However, the effects of or LY294002. In conclusion, UroA protected SH-SY5Y signaling in a SIRT1-dependent manner.