Open AccessOsthole inhibits proliferation of kainic acid‑activated BV‑2 cells by modulating the Notch signaling pathway
Author(s) -
YuZhu Li,
Zheng Sun,
HuaGuo Xu,
Qinggao Zhang,
Zeng Chang-qian
Publication year - 2020
Publication title -
molecular medicine reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.727
H-Index - 56
eISSN - 1791-3004
pISSN - 1791-2997
DOI - 10.3892/mmr.2020.11455
Subject(s) - kainic acid , notch signaling pathway , nitric oxide synthase , signal transduction , western blot , microglia , nitric oxide , tumor necrosis factor alpha , cell growth , apoptosis , microbiology and biotechnology , cell cycle , downregulation and upregulation , biology , cancer research , chemistry , immunology , endocrinology , biochemistry , inflammation , receptor , glutamate receptor , gene
Epilepsy is a syndrome involving chronic recurrent transient brain dysfunction. Activation and proliferation of microglia serve important roles in epilepsy pathogenesis and may be targets for treatment. Although osthole, an active constituent isolated from Cnidium monnieri (L.) Cusson, has been demonstrated to improve epilepsy in rats, its underlying mechanism remains to be elucidated. The present study investigated the effect of osthole on proliferation of kainic acid (KA)‑activated BV‑2 cells and explored the molecular mechanism by which it inhibited their proliferation. Using Cell Counting Kit‑8, enzyme‑linked immunosorbent assay, reverse transcription‑quantitative PCR, western blot analysis and immunofluorescence staining, it was identified that following exposure of KA‑activated BV‑2 cells to 131.2 µM osthole for 24 h, cell proliferation and release of tumor necrosis factor α, interleukin 6 and nitric oxide synthase/induced nitric oxide synthase were significantly inhibited (P<0.05). Further experiments revealed that osthole significantly downregulated mRNA and protein levels of Notch signaling components in KA‑activated BV‑2 cells (P<0.05). Therefore, it was hypothesized that osthole inhibited the proliferation of microglia by modulating the Notch signaling pathway, which may be useful for the treatment of epilepsy and other neurodegenerative diseases characterized by Notch upregulation.