title: Protective effects of dibenzocyclooctadiene lignans from Schisandra chinensis against beta-amyloid and homocysteine neurotoxicity in PC12 cells.
abstract: Aggregated beta-amyloid (Aβ) and elevated plasma levels of homocysteine have been implicated as critical factors in the pathogenesis of Alzheimer's disease. The neuroprotective effects and possible mechanism of four structurally similar dibenzocyclooctadiene lignans (namely schisandrin, schisantherin A, schisandrin B and schisandrin C) isolated from the fruit of Schisandra chinensis (Turcz.) Baill. (Schisandraceae) against Aβ₂₅₋₃₅ and homocysteine toxicity in PC12 cells was studied. Exposure of PC12 cells to 0.5 µm Aβ₂₅₋₃₅ caused significant cell death, increased the number of apoptotic cells, elevated reactive oxygen species, increased the levels of the pro-apoptotic protein Bax and caspase-3 activation. All these effects induced by Aβ₂₅₋₃₅ were markedly reversed by schisandrin B and schisandrin C pretreatment, while schisandrin and schisantherin A had no obvious effects. Meanwhile, schisandrin B and schisandrin C reversed homocysteine-induced cytotoxicity. The results indicated that schisandrin B and schisandrin C protected PC12 cells against Aβ toxicity by attenuating ROS production and modulating the apoptotic signal pathway through Bax and caspase-3. Further structure-activity analysis of Schisandra lignans and evaluations of their neuroprotective effects using AD animal models are warranted.
authors.affiliation: The School of Chinese Medicine, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: Ju-Xian
authors.initials: JX
authors.lastname: Song
authors.forename: Xiang
authors.initials: X
authors.lastname: Lin
authors.forename: Ricky Ngok-Shun
authors.initials: RN
authors.lastname: Wong
authors.forename: Stephen Cho-Wing
authors.initials: SC
authors.lastname: Sze
authors.forename: Yao
authors.initials: Y
authors.lastname: Tong
authors.forename: Pang-Chui
authors.initials: PC
authors.lastname: Shaw
authors.forename: Yan-Bo
authors.initials: YB
authors.lastname: Zhang
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D034242:Cyclooctanes / Q000494:pharmacology*; D004149:Dioxoles; D006710:Homocysteine / Q000633:toxicity*; D017705:Lignans / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000633:toxicity*; D011083:Polycyclic Compounds; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D032141:Schisandra / Q000737:chemistry*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; C494828:Bax protein, rat; D034242:Cyclooctanes; D004149:Dioxoles; D017705:Lignans; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D011083:Polycyclic Compounds; D017382:Reactive Oxygen Species; C074636:amyloid beta-protein (25-35); D051028:bcl-2-Associated X Protein; C510994:dibenzocyclooctadiene lignan; C015499:schizandrin B; D006710:Homocysteine; C034557:schizandrer A; C031409:schizandrin C; C505410:Casp3 protein, rat; D053148:Caspase 3; C011105:schizandrin