Biochanin A protects SH-SY5Y cells against isoflurane-induced neurotoxicity by suppressing oxidative stress and apoptosis

Abstract

Biochanin A (BCA) is a natural organic O-methylated isoflavone with a variety of pharmacological effects, and has been reported to have neuroprotective properties. Here, we explored whether BCA protects neurocytes against isoflurane-induced neurotoxicity and investigated the underlying mechanism. Cell viability was tested by cell counting kit-8 and lactate dehydrogenase release assays. Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and caspase-3/7 activity assays. Superoxide dismutase (SOD) and catalase (CAT) activities and levels of glutathione (GSH) and malondialdehyde (MDA) were measured to assess oxidative stress. Expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase (NQO1) was determined by western blotting. Treatment with BCA significantly attenuated the reduction of cell viability induced by isoflurane in SH-SY5Y cells. In addition, BCA treatment reversed isoflurane-induced SOD and CAT activity reduction, GSH level decline and MDA level increase. Isoflurane-induced apoptosis was also attenuated by treatment with BCA. The increase in nuclear Nrf2, HO-1 and NQO1 expression induced by isoflurane was amplified by treatment with BCA. These inhibitory effects of BCA on isoflurane-induced oxidative stress, viability reduction and cell apoptosis were attenuated in Nrf2 knockdown SH-SY5Y cells. Our findings indicate that BCA protects SH-SY5Y cells against isoflurane-induced neurotoxicity via inducing the Nrf2/ARE pathway.

Keywords: Apoptosis; Biochanin A; Isoflurane; Nrf2/ARE pathway; Oxidative stress; SH-SY5Y cells.