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基于药效学和化学性质的五味子全面质量标志物多维策略研究。

A multidimensional strategy for uncovering comprehensive quality markers of Schisandra chinensis (Turcz.) Baill based on pharmacodynamics and chemical properties.

机构信息

School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.

School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.

出版信息

Phytomedicine. 2022 Nov;106:154273. doi: 10.1016/j.phymed.2022.154273. Epub 2022 Jun 12.

Abstract

BACKGROUND

Quality control of Traditional Chinese Medicines (TCMs) has improved greatly, but there is still a lack of a convincing quality evaluation system for TCMs. Developing quality control markers of TCMs based on pharmacodynamics instead of content has been an attractive approach. However, on account of neglecting phytochemistry attributes of TCMs, part of effective markers might be short of specificity and inconvenient for detecting in production manufacture, which is adverse to control the quality of TCMs systematically.

PURPOSE

To build a novel and multidimensional quality assessment approach for TCMs based on pharmacodynamics and chemical properties.

METHODS

Schisandra chinensis (Turcz.) Baill (S. chinensis) was used as an example and a rat depression model was built by using a chronic unpredictable mild stress procedure. For identifying the antidepressive components of S. chinensis, we elucidated its antidepressant mechanism in first-step by using quantitative RT-PCR and immunoblotting techniques. And accordingly, correlation analysis between ingredients in vivo with target proteins and anti-inflammation experiments in vitro were carried out. On the other hand, HPLC fingerprint combinations with diverse chemometrics methods were applied to analyze 14 preparations of S. chinensis to obtain its characteristic chemical information. Finally, we ascertained the quality control markers of S. chinensis by integrating the efficacious and characteristic constituents.

RESULTS

Our research indicated that S. chinensis treated depression by relieving disordered monoaminergic system and ameliorating neuroinflammation. Five effective substances (schisandrol A, schisandrin A, gomisin N, schisandrin B, and schisandrin C) were screened out according to their potential anti-depression efficacy. Besides, 21 common ingredients and 4 representative constituents of S. chinensis were identified by chemical analysis, whereas only 2 characteristic quantitative markers (schisandrol A, schisandrol B) were ultimately ascertained based on previous studies.

CONCLUSION

6 components, schisandrol A, schisandrin A, gomisin N, schisandrin B, schisandrin C, and schisandrol B, possessed efficacy, measurability, and specificity, were selected as the comprehensive markers for quality control of S. chinensis. We proposed a multidimensional strategy for identifying comprehensive quality markers for TCMs in this study.

摘要

背景

中药(TCM)的质量控制已经有了很大的提高,但仍然缺乏令人信服的 TCM 质量评价体系。基于药效而非含量来开发 TCM 的质量控制标志物一直是一种很有吸引力的方法。然而,由于忽略了 TCM 的植物化学属性,一部分有效的标志物可能缺乏特异性,不方便在生产制造中检测,不利于系统控制 TCM 的质量。

目的

建立一种基于药效学和化学性质的新型多维 TCM 质量评价方法。

方法

以五味子(S. chinensis)为例,采用慢性不可预测轻度应激程序建立大鼠抑郁模型。为了鉴定 S. chinensis 的抗抑郁成分,我们首先使用定量 RT-PCR 和免疫印迹技术阐明其抗抑郁机制。相应地,进行了体内成分与靶蛋白的相关性分析以及体外抗炎实验。另一方面,应用 HPLC 指纹图谱结合多种化学计量学方法对 14 种 S. chinensis 制剂进行分析,以获得其特征化学信息。最后,我们通过整合有效和特征成分来确定 S. chinensis 的质量控制标志物。

结果

我们的研究表明,五味子通过缓解紊乱的单胺能系统和改善神经炎症来治疗抑郁症。根据其潜在的抗抑郁功效,筛选出 5 种有效物质(五味子醇 A、五味子甲素、戈米辛 N、五味子乙素和五味子丙素)。此外,通过化学分析鉴定出 21 种常见成分和 S. chinensis 的 4 种代表性成分,而仅基于先前的研究最终确定了 2 种特征定量标志物(五味子醇 A、五味子醇 B)。

结论

选择 6 种具有功效、可测量性和特异性的成分,即五味子醇 A、五味子甲素、戈米辛 N、五味子乙素、五味子丙素和五味子醇 B,作为五味子综合质量控制标志物。我们在本研究中提出了一种多维策略,用于鉴定 TCM 的综合质量标志物。

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