Schizandrin A ameliorates cognitive functions via modulating microglial polarisation in Alzheimer’s disease mice

Abstract

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 µg/mL lipopolysaccharide or combined with 10 μmol/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 Aβ1-42 (2367.9 ± 431.1 pg/mg) and Aβ1-40 (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.

Keywords:

• Microglial cells
• apoptosis
• cognitive disorder

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by research grants from National Natural Science Foundations of China [81573863], Heilongjiang Postdoctoral Financial Assistance [LBH-Z20193], Research Fund of Heilongjiang University of Traditional Chinese Medicine [2019MS31].