Baicalein protects PC12 cells from Aβ25-35-induced cytotoxicity via inhibition of apoptosis and metabolic disorders

Aims: This study aimed to explore the protective effects and possible mechanisms of baicalein on A beta(25-35)-induced toxicity. Main methods: Thioflavin-T (Th-T) dye was used to determine the effects of baicalein on A beta(25-35) aggregation in vitro. PC12 cells were stimulated with A beta(25-35), then the effects of baicalein on apoptosis, mitochondrial membrane potential (MMP), adenosine triphosphate (ATP), mitochondrial respiratory complex I, reactive oxygen species (ROS) and nitric oxide (NO) levels were determined. Moreover, LC-MS metabolomics approach was used to detect metabolic changes induced by baicalein in A beta(25-35)-injured PC12 cells. Key findings: The results showed that baicalein could inhibit the aggregation of A beta(25-35) in vitro. Furthermore, pretreatment with baicalein significantly prevented A beta(25-35)-induced cell apoptosis, as manifested by increasing the levels of MMP, ATP and mitochondrial respiratory complex I, decreasing the contents of ROS and NO. LC-MS metabolomics revealed that baicalein can regulate 5 metabolites, mainly involving two metabolic pathways, arginine and proline metabolism, nicotinate and nicotinamide metabolism. Significance: Our study revealed that baicalein has a protective effect on A beta(25-35)-induced neurotoxicity in PC12 cells, which may be related to inhibition of apoptosis and metabolic disorders.