title: Oridonin ameliorates neuropathological changes and behavioural deficits in a mouse model of cerebral amyloidosis.
abstract: Alzheimer's disease (AD) is the most common form of neurodegeneration and the major cause of dementia. This multifactorial disorder is clinically defined by progressive behavioural and cognitive deficits, and neuropathologically characterized by β-amyloid aggregation, hyperphosphorylated tau and neuroinflammation. Oridonin, a diterpenoid isolated from Chinese herb Rabdosia rubescens, has multiple biological properties, especially anti-inflammatory and neuroregulatory activities. Potential therapeutic effects of Oridonin were investigated in an animal model of cerebral amyloidosis for AD, transgenic APP/PS1 mice. Oridonin was suspended in carboxymethylcellulose or loaded with a nanostructured emulsion, and was orally administrated or injected. Before, during and following the experimental treatments, behavioural tests were performed with these transgenic mice and their naive littermates. Following relatively short-term treatments of 10 days, brain tissue of mice were removed for immunohistochemical assays. The results indicate that both oral treatment and injection of Oridonin significantly attenuated β-amyloid deposition, plaque-associated APP expression and microglial activation in brain of transgenic mice. Furthermore, injection of Oridonin-nanoemulsion ameliorated deficits in nesting, an important affiliative behaviour, and in social interaction. Additional in vitro studies indicated that Oridonin effectively attenuated inflammatory reaction of macrophage and microglial cell lines. Our results suggest that Oridonin might be considered a promising therapeutic option for human AD or other neurodegenerative diseases.
authors.affiliation: Division of Immunopathology of the Nervous System, Institute of Pathology and Neuropathology, University of Tuebingen, Tuebingen, Germany.
authors.forename: Zhi-Yuan
authors.initials: ZY
authors.lastname: Zhang
authors.forename: Rolf
authors.initials: R
authors.lastname: Daniels
authors.forename: Hermann J
authors.initials: HJ
authors.lastname: Schluesener
mesh_terms: D000284:Administration, Oral; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000686:Amyloidosis / Q000150:complications / Q000188:drug therapy* / Q000473:pathology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D002460:Cell Line; D004195:Disease Models, Animal; D045786:Diterpenes, Kaurane / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D004655:Emulsions; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D007398:Interpersonal Relations; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053758:Nanoparticles / Q000737:chemistry
chemical_list: D016229:Amyloid beta-Peptides; D045786:Diterpenes, Kaurane; D004655:Emulsions; C011959:oridonin
keywords: APP/PS1 transgenic mouse; Alzheimer's disease; cerebral amyloidosis; nanoemulsion; neuroinflammation; non-mnemonic behaviour; oridonin
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