Identifying quality-markers from Shengmai San protects against transgenic mouse model of Alzheimer's disease using chinmedomics approach

Background: Shengmai San (SMS), a Chinese classic herbal formula, has been widely used for the treatment of Qi-Yin deficiency syndrome in Asia. Modern pharmacological studies have shown that SMS improves the cognitive function. However, the quality markers (Q-markers) for SMS still need further research. Purpose: Using chinmedocmics strategy to systematically evaluate the efficacy of SMS in the treatment of APPswe/PS1dE9 (APP/PS1) transgenic model of Alzheimer's disease (AD) and to discover the efficacy-related Q-markers. Methods: The effect of SMS on APP/PS1 mice was evaluated by behavioral test, immunohistochemistry and urine metabolic profile, and the urine marker metabolites associated with SMS treatment of AD were characterized using metabolomics method. In the premise of efficacy, Serum Pharmacochemistry of Traditional Chinese Medicine was applied to investigate the in vivo constituents of SMS. A correlation analysis between marker metabolites of therapeutic effects and serum constituents was completed by chinmedomics approach. Results: SMS had a therapeutic effect on APP/PS1 mice, and 34 potential urine biomarkers were reversed by SMS treatment. A total of 17 in vivo constituents were detected, including 14 prototype components and 3 metabolites. The correlation analysis showed that eight constituents were extremely correlated with protective effects of SMS in AD, and considered as potential Q-markers of SMS, including schisandrin, isoschisandrin, angeloylgomisin Q, gomisin D, angeloylgomisin H, gomisin M2, ginsenoside F1, 20(R)-ginsenoside Rg3. Conclusion: This study has demonstrated that chinmedomics is novel strategy for discovering the potential effective constituents from herbal formula, which are recognized as Q-markers.