4-O-Methylhonokiol Prevents Memory Impairment in the Tg2576 Transgenic Mice Model of Alzheimer's Disease Via Regulation of β-Secretase Activity

Article type: Research Article

Authors: Lee, Young-Jung^{a; b; c; 1} | Choi, Dong-Young^{a; b; c; 1} | Lee, Yong Kyoung^{a; b; c} | Lee, Yoot Mo^a | Han, Sang Bae^{a; b; c} | Kim, Young Hee^d | Kim, Ki Ho^d | Nam, Sang-Yoon^e | Lee, Beom Jun^e | Kang, Jong-Koo^e | Yun, Young Won^e | Oh, Ki-Wan^a | Hong, Jin Tae^{a; b; c; *}

Affiliations: [a] College of Pharmacy, Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk, Korea | [b] Medical Research Center, Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk, Korea | [c] CBITRC, Chungbuk National University, Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk, Korea | [d] R&D Center, Bioland Ltd., Songjeoung, Byongchon, Cheonan-si, Chungnam, Korea | [e] College of Veterinary Medicine and Research Institute of Veterinary Medicine (RIVM), Chungbuk National University, Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk, Korea

Correspondence: [*] Correspondence to: Jin Tae Hong, Ph.D., College of Pharmacy, Chungbuk National University, 12 Gaeshin-dong, Heunduk-gu, Cheongju, Chungbuk 361-763, Korea. Tel.: +1 82 43 261 2813; Fax: +1 82 43 261 8273; E-mail: [email protected].

Note: [1] Both authors contributed equally to this work.

Abstract: 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.

Keywords: 4-O-methylhonokiol, Alzheimer's disease, β-secretase, neuroinflammation, oxidative stress

DOI: 10.3233/JAD-2012-111835

Journal: Journal of Alzheimer's Disease, vol. 29, no. 3, pp. 677-690, 2012