title: Mori Fructus improves cognitive and neuronal dysfunction induced by beta-amyloid toxicity through the GSK-3β pathway in vitro and in vivo.
abstract: BACKGROUND
  A growing body of literature supports the concept that antiaging herbs may be potential candidates for use in treating age-related neurodegeneration, including Alzheimer׳s disease (AD). Mori Fructus is a well-known traditional herbal medicine, food, and dietary supplement. This study employed models of amyloid beta (Aβ)-induced AD to investigate the protective effects of Mori Fructus ethanol extract (ME) against age-related disease and cognitive deficits.
  
  
  METHODS
  To examine the protective effect of ME, we measured cell viability, cytotoxicity, and survival in rat primary hippocampal cultures. We performed behavioral tests and histological analysis in mouse models of AD induced by Aβ(25-35) toxicity. To investigate the mechanism underlying the protective effect, we performed western blotting using antibodies against apoptotic markers as well as the nonphosphorylated and phosphorylated forms of Akt, glycogen synthase kinase-3β (GSK-3β), and tau. We also measured apoptotic marker fluorescence intensity.
  
  
  RESULTS
  ME significantly attenuated Aβ-induced cell damage, enhanced Akt and GSK-3β phosphorylation, and reduced tau phosphorylation. ME reduced apoptotic markers that were activated by GSK-3β, and reduced reactive oxygen species production. Further, ME decreased the B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X expression ratio, mitochondria depolarization, cytochrome c release from mitochondria, and caspase-3 activation. We confirmed that ME treatment improved cognitive impairment and neuronal cell death induced by Aβ(25-35) toxicity in the mouse hippocampus via its antiapoptotic activity.
  
  
  CONCLUSIONS
  These results indicate that ME protects cognition and neurons in AD-like models induced by Aβ via reduction of tau phosphorylation and apoptosis through GSK-3β inactivation.
authors.affiliation: College of Pharmacy and Kyung Hee East-West Pharmaceutical Research Institute, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea; Department of Life and Nanopharmaceutical Science, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Hyo Geun
authors.initials: HG
authors.lastname: Kim
authors.affiliation: Department of Life and Nanopharmaceutical Science, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Gunhyuk
authors.initials: G
authors.lastname: Park
authors.affiliation: Department of Life and Nanopharmaceutical Science, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Soonmin
authors.initials: S
authors.lastname: Lim
authors.affiliation: Department of Life and Nanopharmaceutical Science, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Hanbyeol
authors.initials: H
authors.lastname: Park
authors.affiliation: College of Pharmacy and Kyung Hee East-West Pharmaceutical Research Institute, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Jin Gyu
authors.initials: JG
authors.lastname: Choi
authors.affiliation: College of Pharmacy and Kyung Hee East-West Pharmaceutical Research Institute, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Hyun Uk
authors.initials: HU
authors.lastname: Jeong
authors.affiliation: College of Pharmacy and Kyung Hee East-West Pharmaceutical Research Institute, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Min Seo
authors.initials: MS
authors.lastname: Kang
authors.affiliation: College of Pharmacy, Chungbuk National University, Cheongju 361-763, Republic of Korea.
authors.forename: Mi Kyeong
authors.initials: MK
authors.lastname: Lee
authors.affiliation: College of Pharmacy and Kyung Hee East-West Pharmaceutical Research Institute, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea; Department of Life and Nanopharmaceutical Science, Graduate School, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu, Seoul 130-701, Republic of Korea. Electronic address: msohok@khu.ac.kr.
authors.forename: Myung Sook
authors.initials: MS
authors.lastname: Oh
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism; D016229:Amyloid beta-Peptides; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D005638:Fruit; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000166:cytology; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008813:Mice, Inbred ICR; D031625:Morus; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010446:Peptide Fragments; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D010936:Plant Extracts; C074636:amyloid beta-protein (25-35); D016875:tau Proteins; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; D053148:Caspase 3
keywords: Amyloid beta; Apoptosis; Glycogen synthase kinase-3β; Learning and memory; Mori Fructus; Neuroprotection