NP-3 Effects of Osthole Microemulsion by Nasal Administration on the Cholinergic Pathway in AD Mice  

作　　者：HOU Xue-qin RONG Cui-ping HAO Ji-fu ZHANG Han-ting 

机构地区：[1]Institute of Pharmacology,Taishan Medical University,Shandong,271016,China [2]Guangxi Key Laboratory of Brain and Cognitive Neuroscience,Guilin Medical University,Guilin,China [3]Department of Pharmacy,Taishan Medical University,Shandong,271016,China [4]Departments of Behavioral Medicine&Psychiatry,Physiology&Pharmacology,and Neuroscience,the Rockefeller Neurosciences Institute,West Virginia University Health Sciences Center,Morgantown,WV 26506,USA

出　　处：《神经药理学报》2018年第4期101-102,共2页Acta Neuropharmacologica

基　　金：The present study was supported by research grants from the National Natural Science Foundation of China(grant no.81703901 to Hou XQ),the Shandong Province Natural Science Foundation of China(grant no.ZR2016HB56 to Hou XQ),and the Taian Municipal Science and Technology Bureau funding(grant no:2016NS1078 to Hou XQ).

摘　　要：Objectives:Fructus Cnidii is the dry ripe fruit of Cnidium monnieri(L.)Cuss.,which belongs to the umbelliferous plant.It has long been used in clinic practice and has been found to have pharmacological activity in the central nervous system.Osthole is the main active component of Fructus Cnidii.However,it shows low bioavailability,fast distribution and elimination,and low concentration in the brain when given orally.In this study,we aimed to develop a new dosage form to increase the osthole concentration in the brain and enhance its pharmacological effects in the central nervous system through reducing the dosage while improving the stability and bioavailability.Thus,microemulsion containing osthole was prepared and the effects of osthole microemulsion were examined in the mouse model of Alzheimer’s disease(AD).Methods:On the basis of pseudo-ternary phase diagram,microemulsion was prepared by using polyoxyethlated Cremophor RH40 as emulsifiers,propylene glycol as assistant emulsifiers and ethyl acetate as the oil phase.The particle size and distribution of osthole microemulsion were detected by laser particle size analyzer and transmission election microscope.The content of osthole was determined by UV spectrophotometry.The effects of osthole microemulsion by nasal administration on the learning and memory abilities in scopolamine-treated mice were assessed by Morris water maze and novel object recognition tests.The superoxide dismutase(SOD)activity,glutathione(GSH)levels and malondialdehyde(MDA)contents in the serum were examined to evaluate the oxidant stress.Choline acetyltransferase(ChAT)and acetylcholinesterase(AChE)expression in the olfactory-basal forebrain pathway were detected by immunohistochemical analysis.We also investigated the acetylcholine(ACh)levels and the histological morphology in the brain.Results:The average particle size of 1μg·μL-1 osthole microemulsion was less than 15 nm.It was characterized as spheres under the transmission electron microscopy,and the osthole was completely encapsu

关 键 词：OSTHOLE NANOEMULSIONS Pseudo-ternary phase diagram NASAL administration CHOLINERGIC NERVE circuits 

分 类 号：R73[医药卫生—肿瘤]