Protective effects of dibenzocyclooctadiene lignans from Schisandra chinensis against beta‐amyloid and homocysteine neurotoxicity in PC12 cells |
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Authors: | Ju‐Xian Song Xiang Lin Ricky Ngok‐Shun Wong Stephen Cho‐Wing Sze Yao Tong Pang‐Chui Shaw Yan‐Bo Zhang |
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Institution: | 1. The School of Chinese Medicine, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China;2. Department of Biology, Hong Kong Baptist University, 224 Waterloo Road, Kowloon, Hong Kong SAR, China;3. Department of Biochemistry, The Chinese University of Hong Kong, Shatin, N.T. Hong Kong SAR, China |
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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. Copyright © 2010 John Wiley & Sons, Ltd. |
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Keywords: | Schisandra chinensis (Turcz ) Baill dibenzocyclooctadiene lignans beta‐amyloid homocysteine schisandrin B schisandrin C |
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