title: Natural β-Dihydroagarofuran-Type Sesquiterpenoids as Cognition-Enhancing and Neuroprotective Agents from Medicinal Plants of the Genus Celastrus.
abstract: Alzheimer's disease (AD) is an irreversible, multifaceted, and progressive neurodegenerative disorder. Over the past 30 years, the search for anti-AD drugs has been primarily based on the cholinergic deficiency hypothesis and/or the β-amyloid (Aβ) cascade hypothesis. In this study, we report the identification of 16 new and 38 known β-dihydroagarofuran-type sesquiterpenoids from Celastrus flagellaris and Celastrus angulatus. The β-dihydroagarofuran-type sesquiterpenoids 58, 59, 61, and 63 significantly attenuated scopolamine-induced prolonged escape latency and increased number of errors compared with the control group. At 10 μM, 21 of the 62 tested β-dihydroagarofuran-type sesquiterpenoids rescued Aβ25-35-induced SH-SY5Y cells from viability reduction, which increased the cell viability from 64.6% for the model to more than 74.0%. The majority of the β-dihydroagarofuran-type sesquiterpenoids with ester groups exhibited stronger activity than those with free hydroxy groups or without substituents at the same positions. These results identified a new chemical skeleton as drug lead for the investigation of novel therapeutic agents against AD.
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, People's Republic of China.
authors: Ruonan
authors: R
authors: Ning
authors: CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, People's Republic of China.
authors: Yun
authors: Y
authors: Lei
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, People's Republic of China.
authors: Shuangzhu
authors: S
authors: Liu
authors: CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, People's Republic of China.
authors: Huan
authors: H
authors: Wang
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, People's Republic of China.
authors: Rujun
authors: R
authors: Zhang
authors: CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, People's Republic of China.
authors: Wei
authors: W
authors: Wang
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, People's Republic of China.
authors: Yingdong
authors: Y
authors: Zhu
authors: CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, People's Republic of China.
authors: Haiyan
authors: H
authors: Zhang
authors: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences , Shanghai 201203, People's Republic of China.
authors: Weimin
authors: W
authors: Zhao
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000187:drug effects; D031247:Celastrus / Q000737:chemistry*; D002470:Cell Survival / Q000187:drug effects; D003071:Cognition / Q000187:drug effects; D004952:Esters; D006801:Humans; D015394:Molecular Structure; D018696:Neuroprotective Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000187:drug effects; D010946:Plants, Medicinal / Q000737:chemistry*; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D004952:Esters; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D012717:Sesquiterpenes; C074636:amyloid beta-protein (25-35); C079978:dihydroagarofuran