Schizandrin A Ameliorates Cognitive Functions Via Modulating Microglial Polarisation In Alzheimer'S Disease Mice

PHARMACEUTICAL BIOLOGY(2021)

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摘要
Context Schizandrin A (Sch A) is a major phytochemical from Schisandra chinensis (Turcz.) Baill. (Schisandraceae), which exerts a neuroprotective effect in Alzheimer's disease (AD). Objective To investigate the mechanism of Sch A in AD. Materials and methods AD group: APP/PS1 transgenic mice served as AD models; AD + SCH group: APP/PS1 received 2 mg/kg Sch A by intragastric administration; WT: C57BL/6 mice were used as control. For in vitro assay, mouse microglial BV2 cells were treated with 0.5 mu g/mL lipopolysaccharide or combined with 10 mu mol/L Sch A for 24 h. The cognitive function and apoptosis in the mice was estimated. Microglial polarisation in the mice and cells was analysed. Results Sch A treatment effectively improved spatial learning and memory ability and suppressed apoptosis in the brain tissues of APP/PS1 mice. APP/PS1 mice exhibited an increase in the levels of A beta 1-42 (2367.9 +/- 431.1 pg/mg) and A beta 1-40 (1753.3 +/- 253.4 pg/mg), which was abolished by Sch A treatment. Moreover, Sch A treatment repressed the proportions of iNOS(+)/Iba-1(+) cells and IL-6 expression, while enhanced the proportions of Arg-1(+)/Iba-1(+) cells and IL-10 expression in APP/PS1 mice. In vitro, Sch A treatment reduced the proportions of CD16/32(+) cells, iNOS expression and IL-6 levels (25.7 +/- 5.3 pg/mL) repressed M1 polarisation, and enhanced the proportions of CD206 cells, Arg-1 expression and IL-10 levels (75.9 +/- 12.8 pg/mL) in BV2 cells. Conclusions This research confirms the neuroprotective effect of Sch A in AD, suggesting that Sch A may become a potential anti-AD agent.
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关键词
Microglial cells, apoptosis, cognitive disorder
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