posted on 2021-08-27, 08:30authored byLu Li, Rongsheng Zhou, Haigang Lv, Lei Song, Xiaohong Xue, Li Wu
Luteolin is a flavone compound occurring
in a variety of medicinal
plants, which is reported to have neuroprotective properties. In this
study, we aimed to explore the effects of luteolin in alleviating
sevoflurane-induced neurotoxicity. GeneCards and Traditional Chinese
Medicine Systems Pharmacology Database and Analysis Platform were
employed to screen luteolin, sevoflurane, and neurotoxicity-related
genes. Subsequently, we isolated primary neurons from the hippocampus
of 1-day-old C57BL/6J mice and tested for cytotoxicity after treatment
of different concentrations of luteolin. Next, we measured the expression
of apoptosis by flow cytometry and assessed inflammation-related factors,
including heme oxygenase-1 expression detected by immunohistochemical
staining and neuronal apoptosis. Finally, water maze, open field,
and fear conditioning tests were conducted to observe the interaction
between luteolin and sevoflurane in cognitive impairment of mice.
Luteolin had the lowest cytotoxicity at concentrations of 30 or 60
μg/mL; we selected 30 μg/mL for drug administration experiments in vitro. Luteolin inhibited sevoflurane-induced neuronal
apoptosis and inflammatory responses through the autophagic pathway
and thus ameliorated sevoflurane-induced cognitive impairment in mice.
Mechanistically, luteolin up-regulated heme oxygenase-1 expression,
which activated the autophagy pathway in vitro. This
was confirmed by subsequent histological experiments in mice and behavioral
results showing rescue cognitive impairment. Our findings uncovered
an inhibitory role of luteolin in sevoflurane-induced neuronal apoptosis
and inflammatory response through activation of autophagy arising
from up-regulation of heme oxygenase-1, thereby alleviating sevoflurane-induced
cognitive impairment in mice.