Phloroglucinol Attenuates the Cognitive Deficits of the 5XFAD Mouse Model of Alzheimer's Disease.
Alzheimer's disease (AD) is the most common form of dementia among the elderly. Neuritic plaques whose primary component is amyloid beta peptide (Aβ) and neurofibrillary tangles which are composed of hyperphosphorylated tau, are known to be the neuropathological hallmarks of AD. In addition, impaired synaptic plasticity in neuronal networks is thought to be important mechanism underlying for the cognitive deficits observed in AD. Although various causative factors, including excitotoxicity, mitochondrial dysregulation and oxidative damage caused by Aβ, are involved in early onset of AD, fundamental therapeutics that can modify the progression of this disease are not currently available. In the present study, we investigated whether phloroglucinol (1, 3, 5-trihydroxybenzene), a component of phlorotannins, which are plentiful in Ecklonia cava, a marine brown alga species, displays therapeutic activities in AD. We found that phloroglucinol attenuates the increase in reactive oxygen species (ROS) accumulation induced by oligomeric Aβ1-42 (Aβ1-42) treatment in HT-22, hippocampal cell line. In addition, phloroglucinol was shown to ameliorate the reduction in dendritic spine density induced by Aβ1-42 treatment in rat primary hippocampal neuron cultures. We also found that the administration of phloroglucinol to the hippocampal region attenuated the impairments in cognitive dysfunction observed in 22-week-old 5XFAD (Tg6799) mice, which are used as an AD animal model. These results indicate that phloroglucinol displays therapeutic potential for AD by reducing the cellular ROS levels.
Department of Pharmacology and Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Republic of Korea.
Eun-Jeong
EJ
Yang
Department of Pharmacology and Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Republic of Korea.
Sangzin
S
Ahn
Department of Pharmacology and Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Republic of Korea.
Junghwa
J
Ryu
Department of Pharmacology and Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Republic of Korea.
Moon-Seok
MS
Choi
Department of Pharmacology and Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Republic of Korea.
Shinkyu
S
Choi
Department of Microbiology, School of Medicine, Ewha Womans University, Seoul, Republic of Korea.
Young Hae
YH
Chong
Department of Biochemistry, School of Medicine, Jeju National University, Jeju, Republic of Korea.
Jin-Won
JW
Hyun
Department of Foods and Nutrition, College of Natural Science, Kookmin University, Seoul, Republic of Korea.
Moon-Jeong
MJ
Chang
Department of Pharmacology and Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Republic of Korea; Seoul National University College of Medicine, Bundang Hospital, Bundang-Gu, Sungnam, Republic of Korea; Neuroscience Research Institute, College of Medicine, Seoul National University, Seoul, Republic of Korea.
Hye-Sun
HS
Kim
D000544:Alzheimer Disease / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000633:toxicity; D000818:Animals; D002460:Cell Line; D003071:Cognition / Q000187:drug effects*; D049229:Dendritic Spines / Q000187:drug effects; D004195:Disease Models, Animal; D000076122:Disks Large Homolog 4 Protein; D005260:Female; D051528:Guanylate Kinases / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D010446:Peptide Fragments / Q000737:chemistry / Q000633:toxicity; D010696:Phloroglucinol / Q000494:pharmacology* / Q000627:therapeutic use; D011247:Pregnancy; D055503:Protein Multimerization / Q000187:drug effects; D017433:Protein Structure, Secondary; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013569:Synapses / Q000187:drug effects; D016708:Synaptophysin / Q000378:metabolism
D016229:Amyloid beta-Peptides; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D008565:Membrane Proteins; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; D016708:Synaptophysin; C075222:amyloid beta-protein (1-42); D010696:Phloroglucinol; D051528:Guanylate Kinases