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基于化学计量学分析和生物测定指导的从打通颗粒中鉴定具有促进肠道动力作用的有效化合物。

Chemometric-based analysis and bioassay guided identification of potent compounds with intestinal motility promoting effects from Dalitong Granules.

作者信息

Ma Jiayi, Su Yan, Xie Jingru, Tao Lin, Zhao Yan, Wang Xiaoxia, Kuang Zhenying, Sheng Xianjie, Kang An, Aa Jiye, Wang Guangji

机构信息

School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.

School of Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China.

出版信息

J Ethnopharmacol. 2025 Jan 30;337(Pt 1):118777. doi: 10.1016/j.jep.2024.118777. Epub 2024 Sep 3.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Dalitong Granules (DLT), a potent Traditional Chinese Medicine known for its ability to promote gastrointestinal motility, is widely used in clinical practice for the treatment of Functional Dyspepsia (FD). Despite the remarkable clinical efficacy of DLT, the specific components responsible for its effectiveness remains unclear.

AIM OF THE STUDY

The study aimed to identify potential active ingredients of DLT for treating FD through spectrum-effect relationship analysis, multivariate statistical analysis and network pharmacology analysis. The efficacy of these identified compounds was subsequently validated using the zebrafish intestinal peristalsis model.

MATERIALS AND METHODS

The fingerprints of various solvent-extracted DLT were analyzed using high performance liquid chromatography coupled with tandem high-resolution mass spectrometry. The intestinal motility-promoting activities of DLT extracted by different solvents were evaluated through an intestinal propulsion test in mice. Potential therapeutic substances in DLT for treating FD were screened via chemometric analysis based on spectrum-effect relationship analysis. The correlation between the intensity of common peaks in the total ion chromatogram and the pharmacodynamic indices was assessed using multivariate statistical analysis. Additionally, given the complexity of Traditional Chinese Medicine, which comprises multiple components and targets, a network pharmacology analysis was performed to investigate the potential active ingredients in DLT. Finally, the pharmacological effects of these compounds in DLT were validated using a zebrafish intestinal motility model.

RESULTS

Through spectral-effect relationships analysis and network pharmacology analysis, it was determined that ten ingredients in DLT contribute to the promotion of intestinal motility. In a zebrafish intestinal motility model, it was observed that eight chemicals (excluding tetrahydropalmatine) demonstrate favorable activity of promoting gastrointestinal motility. These findings suggest that these ingredients may serve as potential therapeutic agents for improving gastric motility disorders.

CONCLUSIONS

This study employed spectral-effect relationship and network pharmacology analysis to identify the active ingredients in DLT. The findings were then validated using a zebrafish intestinal peristalsis model. These results provide a scientific foundation for the clinical application of DLT as a key traditional herbal formula for managing FD.

摘要

民族药理学相关性

达立通颗粒(DLT)是一种具有促进胃肠动力作用的中药,广泛用于治疗功能性消化不良(FD)的临床实践。尽管 DLT 的临床疗效显著,但对于其有效性的具体成分仍不清楚。

研究目的

本研究旨在通过谱效关系分析、多变量统计分析和网络药理学分析,鉴定 DLT 治疗 FD 的潜在活性成分。随后使用斑马鱼肠道蠕动模型验证这些鉴定化合物的功效。

材料和方法

采用高效液相色谱-串联高分辨质谱法分析各种溶剂提取的 DLT 的指纹图谱。通过小鼠肠推进试验评价不同溶剂提取的 DLT 的促肠动力活性。基于谱效关系分析,通过化学计量学分析筛选 DLT 治疗 FD 的潜在治疗物质。采用多变量统计分析评估总离子色谱中共有峰强度与药效学指标之间的相关性。此外,鉴于中药的复杂性,包括多种成分和靶点,采用网络药理学分析研究 DLT 的潜在活性成分。最后,使用斑马鱼肠道蠕动模型验证这些化合物在 DLT 中的药理作用。

结果

通过谱效关系分析和网络药理学分析,确定 DLT 中的十种成分有助于促进肠道蠕动。在斑马鱼肠道蠕动模型中,观察到八种化学物质(不包括延胡索乙素)具有良好的促进胃肠动力活性。这些发现表明,这些成分可能作为改善胃动力障碍的潜在治疗剂。

结论

本研究采用谱效关系和网络药理学分析鉴定了 DLT 的活性成分。然后使用斑马鱼肠道蠕动模型对鉴定结果进行了验证。这些结果为 DLT 作为治疗 FD 的关键传统草药配方的临床应用提供了科学依据。

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