4-O-methylhonokiol prevents memory impairment in the Tg2576 transgenic mice model of Alzheimer's disease via regulation of β-secretase activity.

Alzheimer's disease (AD), the most common form of dementia, is characterized by memory deficits and deposition of amyloid-β (Aβ) in the brain. It has been known that neuroinflammation and oxidative stress are critical factors in the development of AD. 4-O-methylhonokiol, an extract from Magnolia officinalis, is known to have anti-inflammatory and anti-oxidative effects. Thus, we investigated the properties of 4-O-methylhonokiol against progression and development of AD in Tg2576 mice. Tg2576 mice models show memory impairment and AD-like pathological features including Aβ deposition. Oral administration of 4-O-methylhonokiol through drinking water (1 mg/kg in 0.0002% Tween 80) for 12 weeks not only prevented memory impairment but also inhibited Aβ deposition. In addition, 4-O-methylhonokiol decreased β-secretase activity, oxidative lipid and protein damage levels, activation of astrocytes and microglia cells, and generation of IL-1β and TNF-α with increase of glutathione level in the brain. Our results showed that 4-O-methylhonokiol effectively prevented memory impairment by down-regulating β-secretase activity through inhibition of oxidative stress and neuroinflammatory responses in Tg2576 transgenic mice.