title: Neuroprotective effect of Chunghyuldan from amyloid beta oligomer induced neuroinflammation in vitro and in vivo.
abstract: Microglia-mediated inflammation is a major pathological mechanism contributing to Alzheimer's disease (AD), and has been proposed as a potential therapeutic target. Chunghyuldan (CHD; Qingxue-dan in Chinese and Daio-Orengedokuto in Japanese) possesses wide-ranging biological effects, including anti-hyperlipidemic, anti-stroke, anti-inflammatory, and antioxidant activities that could affect neurological functions. In this study, we examined the effects of CHD in in-vitro and in-vivo models of AD induced by the oligomeric form of amyloid-beta (Aβ oligomer), which acts directly on microglia-mediated neuroinflammation to result in neuronal damage and cognitive impairment. CHD at 0.1-100 μg·mL(-1) significantly protected PC12 cells and rat primary hippocampal cells from Aβ oligomer1-42 toxicity. In addition, CHD at 1-10 μg·mL(-1) inhibited Aβ oligomer1-42 induced production of nitric oxide, tumor necrosis factor-α, and interleukin-1β in microglial cells. In an in-vivo AD model, administration of CHD (50 mg·(kg body mass)(-1), for 5 days, per oral) inhibited the activation of astrocytes and microglia in the dentate gyrus and neuronal damage in the CA1 of the ipsilateral hippocampus. Moreover, CHD ameliorated cognitive impairment induced by Aβ oligomer1-42 toxicity. These results demonstrate the neuroprotective effects of CHD through inhibition of microglia-mediated neuroinflammation in in-vitro and in-vivo AD-like models induced by Aβ oligomer1-42 toxicity.
authors.affiliation: a Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, #1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Hyo Geun
authors.initials: HG
authors.lastname: Kim
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Wei-Wan
authors.initials: WW
authors.lastname: Whang
authors.forename: Myung Sook
authors.initials: MS
authors.lastname: Oh
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003071:Cognition / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000378:metabolism; D010446:Peptide Fragments / Q000633:toxicity*; D061251:Primary Cell Culture; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; C499382:Chunghyuldan; D004365:Drugs, Chinese Herbal; D053583:Interleukin-1beta; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C075222:amyloid beta-protein (1-42); D009569:Nitric Oxide
keywords: Alzheimer’s disease; Chunghyuldan; forme oligomère du β-amyloïde; maladie d’Alzheimer; neuro-inflammation; neuroinflammation; oligomeric form of amyloid-beta