Alisol A attenuates Sevoflurane-induced hippocampal neuron injury via targeting SIRT3

To investigate the effects of Alisol A on Sevoflurane (Sev)-induced neuroinflammation in hippocampal HT22 cells and explores the underlying mechanisms involving Sirtuin 3 (SIRT3) activation. Neuroinflammation was induced through the exposure of HT22 cells were exposed to 4% for 6 h. We evaluated cell viability through cell counting kit-8 (CCK-8) assays, apoptosis and ferroptosis through flow cytometry (FCM) and immunoblot assays. Alisol A effects at different concentrations (0, 2.5, 5, 10 and 20 µM) on Sev-induced cell damage were examined. Additionally, using the SIRT3 inhibitor 3-(Benzylamino)-3-Methylbutanoic Acid (3-TYP), SIRT3’s role in mediating these effects was investigated. Alisol A significantly increased Sev-induced HT22 cell viability and inhibited Sev-induced apoptosis and ferroptosis. Alisol A treatment decreased levels of apoptotic markers (Bcl-2 associated X protein (Bax), cleaved caspase-3, cleaved poly ADP-ribose polymerase (PARP)) and ferroptosis markers (MDA, GSH), while increasing expressions of SIRT3 and ferroptosis inhibitors (glutathione peroxidase 4 (GPX4), Solute Carrier Family 7 Member 11 (SLC7A11)). Alisol A’s protective effects were reversed by 3-TYP, confirming SIRT3 activation involvement. Alisol A mitigates Sev-induced neuroinflammation and cell damage in HT22 cells by activating SIRT3. Alisol A may therefore be a promising drug for treating Sev-induced neurotoxicity.

Sevoflurane (Sev); Alisol A; Neuroinflammation; Ferroptosis; SIRT3

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