Baicalein is one of the major
flavonoids in Scutellaria baicalensis Georgi and possesses various effects, including cytoprotection and anti-
inflammation. Because endoplasmic reticulum (ER) stress has been implicated in
neurodegenerative diseases, such as
Alzheimer's disease,
Parkinson's disease, and
cerebral ischemia, we investigated the effects of
baicalein on apoptotic death of HT22 mouse hippocampal neuronal cells induced by
thapsigargin (TG) and
brefeldin A (BFA), two representative ER stress inducers. Apoptosis,
reactive oxygen species (ROS) production, and mitochondrial membrane potential (
MMP) were measured by flow cytometry. Expression level and phosphorylation status of ER stress-associated
proteins and activation and cleavage of apoptosis-associated
proteins were analyzed by Western blot.
Baicalein reduced TG- and BFA-induced apoptosis of HT22 cells and activation and cleavage of apoptosis-associated
proteins, such as
caspase-12 and -3 and
poly(ADP-ribose) polymerase.
Baicalein also reduced the TG- and BFA-induced expression of ER stress-associated
proteins, including
C/EBP homologous protein (CHOP) and
glucose-regulated
protein 78, the cleavage of X-box binding protein-1 and activating
transcription factor 6α, and the phosphorylation of eukaryotic initiation factor-2α and
mitogen-activated protein kinases, such as p38, JNK, and ERK. Knock-down of CHOP expression by
siRNA transfection and specific inhibitors of p38 (
SB203580), JNK (
SP600125), and ERK (
PD98059) as well as
anti-oxidant (
N-acetylcysteine) reduced TG- or BFA-induced cell death.
Baicalein also reduced TG- and BFA-induced ROS accumulation and
MMP reduction. Taken together, these results suggest that
baicalein could protect HT22 neuronal cells against ER stress-induced apoptosis by reducing CHOP induction as well as ROS accumulation and mitochondrial damage.