Magnolol and honokiol prevent learning and memory impairment and cholinergic deficit in SAMP8 mice.
The therapeutic use of neurotrophic factors to treat neurodegenerative disorders, including Alzheimer's disease, is considered feasible. Magnolol and honokiol, constituents of the Magnolia plant, are small organic compounds with neurotrophic activity. We investigated whether magnolol and honokiol can prevent age-related learning and memory impairment and cholinergic deficits in senescence-accelerated mice (SAM). Magnolol (1, 10 mg/kg) or honokiol (0.1, 1 mg/kg) were orally administered to SAMP8 mice once a day for 14 days in 2-month-old mice. Learning and memory performance were evaluated by passive avoidance tests and location and object novelty recognition tests. SAMP8 mice showed significant impairment of learning and memory at 4 and 6 months of age. This age-related learning and memory impairment was prevented by pretreatment with either magnolol (10 mg/kg) or honokiol (1 mg/kg). Cholinergic neuron densities in the medial septum and vertical limb of the diagonal band of the forebrain were evaluated by an immunohistochemical analysis of choline acetyltransferase (ChAT). SAMP8 mice showed a significant cholinergic deficit at 6 months of age. These age-related cholinergic deficits were prevented by treatment with either magnolol (10 mg/kg) or honokiol (1 mg/kg). Moreover, SAMP8 mice showed decreased activity of Akt, a member of the prosurvival pathway, in the forebrain at 2 months of age. A 14-day treatment with either magnolol (10 mg/kg) or honokiol (1 mg/kg) enhanced phosphorylation of Akt in the forebrain at 2 months of age. These results suggest that magnolol and honokiol prevent age-related learning and memory impairment by preserving cholinergic neurons in the forebrain. These compounds may have potential therapeutic applications to various neurodegenerative disorders.
Matsui
Nobuaki
N
Faculty of Pharmaceutical Sciences, Tokushima Bunri University, 180 Nishihama-bouji, Yamashiro-cho, Tokushima City, Tokushima 770-8514, Japan. matsui@ph.bunri-u.ac.jp
Takahashi
Kazuki
K
Takeichi
Miho
M
Kuroshita
Touma
T
Noguchi
Kaori
K
Yamazaki
Kana
K
Tagashira
Hideaki
H
Tsutsui
Kenichi
K
Okada
Hideki
H
Kido
Yuki
Y
Yasui
Yumiko
Y
Fukuishi
Nobuyuki
N
Fukuyama
Yoshiyasu
Y
Akagi
Masaaki
M
D000109:Acetylcholine / Q000378:metabolism; D000375:Aging / Q000187:drug effects*; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001713:Biphenyl Compounds / Q000008:administration & dosage*; D015153:Blotting, Western; D002452:Cell Count; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D007150:Immunohistochemistry; D017705:Lignans / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000008:administration & dosage; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D021641:Recognition, Psychology / Q000187:drug effects*
D001713:Biphenyl Compounds; D004365:Drugs, Chinese Herbal; D017705:Lignans; D010936:Plant Extracts; D019001:Nitric Oxide Synthase; D051057:Proto-Oncogene Proteins c-akt; D000109:Acetylcholine