Baicalin suppresses neuron autophagy and apoptosis by regulating astrocyte polarization in pentylenetetrazol-induced epileptic rats and PC12 cells

[Display omitted] •A1 polarization leads to abnormal autophagy and apoptosis.•Epileptic seizure leads to more A1 astrocytes phenotype.•A1 polarization promotes brain edema and swelling of the cells in the hippocampal dentate gyrus (DG) regions.•Baicalin plays an antiepileptic role by regulating astrocyte phenotype to maintain systemic homeostasis. Epilepsy is a common chronic neurological disorder worldwide, but its entire pathology remains unknown. The purpose of this study was to explore the antiepileptic effect of baicalin (BAL), the main bioactive component of scutellaria. We isolated astrocytes from neonatal rats and astrocytes were identified by glial fibrillary acidic protein (GFAP) immunostaining. The viability and phenotype of astrocytes were determined by Cell Counting Kit-8 (CCK-8) and immunofluorescence staining, respectively. For investigating the effect of BAL on the autophagy in A1 astrocytes treated PC12 cells, expression of light chain 3B (LC3-B) and sequestosome 1 (P62) was analyzed by immunofluorescence staining and apoptosis by acridine orange/ethidium bromide (AO/EB) staining, respectively. For animal experiments, pentylenetetrazol (PTZ)-induced epileptic model was used to explore the antiepileptic effect of BAL. The results showed that BAL reduced lipopolysaccharide (LPS)-induced complement C3 (C3, a marker of A1 astrocytes) + A1 cells and decreased autophagy and apoptosis in PC12 cells. Further findings showed seizure grade and latency were positively correlated with GFAP+/C3 + A1 cells’ infiltration in interstitial astrocytes. After BAL treatment, epileptogenesis was ameliorated with decreased A1 astrocytes in the brain and improved behavioral performance. The enzyme-linked immunosorbent assay (ELISA) showed that the levels of interleukin-1α (IL-1α) and tumor necrosis factor-α (TNF-α) were reduced in the cerebral interstitial site in the BAL group compared to the PTZ group. Western blotting analysis showed that BAL treatment reduced expression of C3, inward rectifier potassium channel Kir4.1, aquaporin-4 (AQP4) in the frontal cortex and Caspase-3, BCL2-associated X protein (Bax) in the hippocampus. In conclusion, these findings suggest that BAL can prevents cognitive and emotional disorders and has antiepileptic effects in rats, which may be associated with suppresses neuron autophagy and apoptosis in the hippocampus via regulate astrocyte phenotypes.