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. 2020 Mar;10(3):557-568.
doi: 10.1016/j.apsb.2019.10.008. Epub 2019 Oct 30.

A systematic strategy for screening therapeutic constituents of Schisandra chinensis (Turcz .) Baill infiltrated blood-brain barrier oriented in lesions using ethanol and water extracts: a novel perspective for exploring chemical material basis of herb medicines

Yiwen Zhang  1 , Xinyan Lv  2 , Jiameng Qu  2 , Xin Zhang  1 , Mingyang Zhang  1 , Hao Gao  1 , Qian Zhang  1 , Ran Liu  1 , Huarong Xu  1 , Qing Li  1 , Kaishun Bi  1
Affiliations

A systematic strategy for screening therapeutic constituents of Schisandra chinensis (Turcz .) Baill infiltrated blood-brain barrier oriented in lesions using ethanol and water extracts: a novel perspective for exploring chemical material basis of herb medicines

Yiwen Zhang et al. Acta Pharm Sin B. 2020 Mar.

Abstract

Schisandra chinensis, a widely used Chinese herbal medicine, was considered as central nervous system (CNS) drug for years. Both ethanol extracts (EES) and water extracts (WES) of it were applied clinically. Unfortunately, the difference of their efficacy and even effective material foundation of S. chinensis remains obscure. In this study, to explore the active constituents of S. chinensis, we compared pharmacodynamics and chemical profiles in vitro/in vivo of EES/WES for the first time using multiple chemical analysis, pharmacological and data processing approaches. It was proved that there was no significant difference in the anti-depressive effects between WES and EES. However, the contents of most components in vitro and in plasma were higher in EES than those in WES, which was unconvincing for their similar efficacy. Therefore, we further explored components of S. chinensis targeted onto brain and the results showed that 5 lignans were identified with definite absorptivity respectively both in EES and WES caused by the limitation of blood-brain barrier. Moreover, bioinformatic analysis predicted their anti-depressive action. Above all, the systematic strategy screened 5 brain-targeted effective substances of S. chinensis and it was suggested that exploring the components into nidi would promote the studies on herbs effective material basis.

Keywords: Chemical profiles; Components into nidi; Effective material basis; Ethanol extracts; Pharmacodynamics; Schisandra chinensis; Traditional Chinese medicine; Water extracts.

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Figures

Image 1
Graphical abstract
Figure 1
Figure 1
The research strategy for finding the material basis for efficacy of Schisandra chinensis by comparing the chemical profiles and pharmacodynamics of EES and WES.
Figure 2
Figure 2
(A) The immobility time in FST of groups. (B) The travel paths in the locomotor activity test. (C) The latency time to feed in NSF test. (D) The level of corticosterone in plasma samples. Values shown are means ± SD, n=6; #P < 0.01 compared with control group; *P < 0.05, **P < 0.01 compared with model group.
Figure 3
Figure 3
Effects of EES and WES on inflammation markers. Values shown are means ± SD; #P < 0.01 compared with control group; *P < 0.05, **P < 0.01 compared with CUMS.
Figure 4
Figure 4
TCC of (A) plasma and (B) brain samples in positive ion mode.
Figure 5
Figure 5
Peak areas of lignans corrected by Bifendate in vitro. For statistical significance, *P < 0.05, **P < 0.01.
Figure 6
Figure 6
Peak areas of lignans corrected by Bifendate in vivo. (A) Contents in plasma samples. (B) Contents in brain samples. For statistical significance, *P < 0.05, **P < 0.01.
Figure 7
Figure 7
Pathways of all active chemical compositions based on bioinformation analysis.
Figure 8
Figure 8
The enrichment degree of target pathways on function groups. Corresponding functional groups related to schisandrol A, gomisin J, schisandrin A, schisandrin B and gomisin N respected with relevant color, respectively.
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