Alleviation of Kainic Acid-Induced Brain Barrier Dysfunction by 4-O-Methylhonokiol in In Vitro and In Vivo Models

Abstract EN

This experiment was designed to investigate whether 4-O-methylhonokiol (MH), a principal ingredient of Magnolia (M.) officinalis bark, alleviated acute intraperitoneal (i.p.) kainic acid- (KA-) induced brain blood barrier dysfunction (BBBD) via pathological examination and cytological analyses of the brain tissues of mice.

KA (10–30 mg/kg) time- and dose-dependently increased the water content of brain tissues and induced edema and encephalopathy.

However, pretreatment with MH (5 and 20 mg/kg, i.p.) significantly reduced the water content of the brain compared to that observed in the KA control group.

Furthermore, MH significantly and dose-dependently reversed the remarkable variations in evan’s blue dye (EBD) staining and malondialdehyde (MDA) levels that were induced by KA (10 mg/kg, i.p.).

MH also decreased the elevated seizure scores that were induced by KA (10 mg/kg, i.p.) in mice in a manner similar to scavengers such as DMTU and trolox.

Additionally, MH significantly scavenged intracellular ROS and Ca2+ within hippocampal cells.

The tight junction seals mediated by claudin (Cld-5) were also found to be modulated by MH.

MH efficiently reduced 1,1-diphenyl-2-picrylhydrazyl (DPPH) (IC50, 52.4 mM) and •OH with an electron spin resonance (ESR) signal rate constant of 4 × 10 9 M - 1 · S - 1 , which is close to the reactivity of the vitamin E analog trolox.

Taken together, these results suggest that MH may enhance radical scavenging in lipid and hydrophobic environments, which may be important for the physiological activity of the barrier.