解毒三根汤抗结直肠癌生物活性成分：天然药物开发的全新综合研究策略

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-04-21 DOI:10.1016/j.phymed.2025.156795

Xueer Zheng , Chao Shi , Ying Xie , Qing Wen , Tongdan Lyu , Hao Li , Zhenru Wang , Minhe Shen , Ying Zhu , Shanming Ruan

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引用次数: 0

摘要

背景节度三仙煎剂（JSD）因其良好的临床疗效在中国南方被广泛用于治疗结直肠癌（CRC）患者，但其有效活性成分仍不为人知。方法采用UPLC-MS/MS筛选JSD和大鼠血浆中的生物活性成分，并结合机器学习进行网络药理学分析，得出最有潜力的生物活性成分。利用RNA-seq技术筛选JSD作用于SW620细胞前后的治疗靶点，并利用生物信息学分析这些关键靶点的临床意义。分子对接、分子动力学模拟和实验验证了最有前景的生物活性成分及其治疗靶点。UPLC-MS/MS筛选出了JSD进入血液的18种原型成分和8种可能的代谢物。网络药理学结合机器学习确定了三种最有前景的生物活性成分。RNA 测序和生物信息学分析揭示了 JSD 对抗 CRC 的六个关键靶点。分子对接和分子动力学模拟提出了最有希望的 "小分子药物-靶蛋白 "组合，SPR和MST证明了它们之间的直接结合：白藜芦醇-CA9、染料木素-NOTUM和阿夫泽林-DPEP1。分子生物学实验发现，白藜芦醇可通过CA9/PI3K/AKT信号通路促进CRC凋亡，而染料木素则以NOTUM为靶标，下调β-catenin的表达，从而抑制CRC的增殖。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Bioactive components of Jiedu Sangen decoction against colorectal cancer: A novel and comprehensive research strategy for natural drug development

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Bioactive components of Jiedu Sangen decoction against colorectal cancer: A novel and comprehensive research strategy for natural drug development

Background

Jiedu Sangen Decoction (JSD) is widely used in the treatment of colorectal cancer (CRC) patients in southern China due to its good clinical efficacy, but the effective active ingredients are still unknown.

Purpose

This study fully explored the bioactive components of JSD based on an innovative and comprehensive research strategy. Using advanced computer technology (e.g., machine learning AHP-SOM algorithm and molecular dynamics simulation) to identify the most promising bioactive components and key targets in JSD, in order to provide new perspectives for the development of natural drugs.

Methods

UPLC-MS/MS was used to screen bioactive components in JSD and rat plasma, and network pharmacology analysis combined with machine learning yielded the most promising bioactive components. RNA-seq was used to screen therapeutic targets before and after JSD acted on SW620 cells, and bioinformatics was used to analyze the clinical significance of these key targets. Molecular docking, molecular dynamics simulation, and experiments verified the most promising bioactive components and their therapeutic targets.

Results

JSD exhibited a strong pro-apoptotic effect on CRC in vitro. UPLC-MS/MS screened out 18 prototype components and 8 possible metabolites of JSD entering the blood. Network pharmacology combined with machine learning identified the three most promising bioactive components. RNA sequencing and bioinformatics analysis revealed six key targets of JSD against CRC. Molecular docking and molecular dynamics simulations proposed the most promising "small molecule drug-target protein" combinations, and SPR and MST demonstrated the direct binding between them: Resveratrol - CA9, Genistein - NOTUM, and Afzelin - DPEP1. Molecular biology experiments found that resveratrol may promote CRC apoptosis through the CA9/PI3K/AKT signaling pathway, and genistein targets NOTUM to downregulate β-catenin expression to inhibit CRC proliferation.

Conclusion

It is feasible to develop a novel and comprehensive research strategy to fully explore bioactive components of JSD and provide full support for natural drug development.

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来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.