gomisin-d and schizandrin

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.. 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.. 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.. 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.. This study has demonstrated that chinmedomics is novel strategy for discovering the potential effective constituents from herbal formula, which are recognized as Q-markers.

Topics: Alzheimer Disease; Animals; Biomarkers, Pharmacological; Cyclooctanes; Dioxoles; Disease Models, Animal; Drug Combinations; Drugs, Chinese Herbal; Ginsenosides; Lignans; Male; Medicine, Chinese Traditional; Metabolomics; Mice, Transgenic; Neuroprotective Agents; Polycyclic Compounds

This study was performed to use UHPLC-QTOF/MSE technology to rapidly search and identify variations of chemical ingredients between Fructus Schisandrae Chinensis and its processed products. The present study provides a basis for the study of Chinese herbal medicine processing with a focus on the impact of processing on chemical components. Using a time-dependent data scan mode (MSE) couple with metabolomics technology, we acquired accurate data and identified the potential chemical markers. A total of 12 chemical markers were identified in the crude, \ vinegar-processed and wine-processed Schisandra chinensis fruit; The results showed that the levels of 6-O-benzoylgomisin O, schisantherin B, schisantherin C, schisantherin D and neokadsuranic acid are the highest in crude Schisandra chinensis fruit; thelevels of schizandrin A, schizandrin B, schizandrin C, gomisin D and gomisin T are the highest in wine-processed Schisandra chinensis fruit; the levels of schisantherin A and schisandrin are the highest in vinegar-processed Schisandra chinensis fruit. There were significant changes of chemical components between Fructus Schisandrae Chinensis and their processed products, and these findings may offer a reasonable explanation for variation of efficacy and clinical applications in the processed products of Fructus Schisandrae Chinensis.

Topics: Chromatography, High Pressure Liquid; Cyclooctanes; Dioxoles; Drugs, Chinese Herbal; Fruit; Lignans; Metabolomics; Polycyclic Compounds; Schisandra

Structure-activity relationship for the inhibition of Schisandra chinensis's ingredients toward (Uridine-Diphosphate) UDP-glucuronosyltransferases (UGTs) activity was performed in the present study. In vitro incubation system was employed to screen the inhibition capability of S. chinensis's ingredients, and in silico molecular docking method was carried out to explain possible mechanisms. At 100 μM of compounds, the activity of UGTs was inhibited by less than 90% by schisandrol A, schisandrol B, schisandrin, schisandrin C, schisantherin A, gomisin D, and gomisin G. Schisandrin A exerted strong inhibition toward UGT1A1 and UGT1A3, with the residual activity to be 7.9% and 0% of control activity. Schisanhenol exhibited strong inhibition toward UGT2B7, with the residual activity to be 7.9% of control activity. Gomisin J of 100 μM inhibited 91.8% and 93.1% of activity of UGT1A1 and UGT1A9, respectively. Molecular docking prediction indicated different hydrogen bonds interaction resulted in the different inhibition potential induced by subtle structure alteration among schisandrin A, schisandrin, and schisandrin C toward UGT1A1 and UGT1A3: schisandrin A > schisandrin > schisandrin C. The detailed inhibition kinetic evaluation showed the strong inhibition of gomisin J toward UGT1A9 with the inhibition kinetic parameter (Ki ) to be 0.7 μM. Based on the concentrations of gomisin J in the plasma of the rats given with S. chinensis, high herb-drug interaction existed between S. chinensis and drugs mainly undergoing UGT1A9-mediated metabolism. In conclusion, in silico-in vitro method was used to give the inhibition information and possible inhibition mechanism for S. chinensis's components toward UGTs, which guide the clinical application of S. chinensis.

Topics: Animals; Cyclooctanes; Dioxoles; Drugs, Chinese Herbal; Glucuronosyltransferase; Herb-Drug Interactions; Lignans; Plant Extracts; Polycyclic Compounds; Rats; Schisandra; Structure-Activity Relationship