An optimal combination of four active components in Huangqin decoction for the synergistic sensitization of irinotecan against colorectal cancer.

IF 5.3 3区医学 Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE

Chinese Medicine Pub Date : 2024-07-02 DOI:10.1186/s13020-024-00967-1

Hongyan Zhou, Dingxin Hu, Xian Zhao, Siyuan Qin, Qiyao Nong, Yuan Tian, Zunjian Zhang, Haijuan Dong, Pei Zhang, Fengguo Xu

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Abstract

Background: Irinotecan (CPT-11) is a first-line treatment for advanced colorectal cancer (CRC). Four components (baicalin, baicalein, wogonin, and glycyrrhizic acid) derived from Huangqin Decoction (HQD) have been proven to enhance the anticancer activity of CPT-11 in our previous study.

Objective: This study aimed to determine the optimal combination of the four components for sensitizing CPT-11 as well as to explore the underlying mechanism.

Methods: The orthogonal design method was applied to obtain candidate combinations (Cmb1-9) of the four components. The influence of different combinations on the anticancer effect of CPT-11 was first evaluated in vitro by cell viability, wound healing ability, cloning formation, apoptosis, and cell cycle arrest. Then, a CRC xenograft mice model was constructed to evaluate the anticancer effect of the optimal combination in vivo. Potential mechanisms of the optimal combination exerting a sensitization effect combined with CPT-11 against CRC were analyzed by targeted metabolomics.

Results: In vitro experiments determined that Cmb8 comprised of baicalin, baicalein, wogonin, and glycyrrhizic acid at the concentrations of 17 μM, 47 μM, 46.5 μM and 9.8 μM respectively was the most effective combination. Importantly, the cell viability assay showed that Cmb8 exhibited synergistic anticancer activity in combination with CPT-11. In in vivo experiments, this combination (15 mg/kg of baicalin, 24 mg/kg of baicalein, 24 mg/kg of wogonin, and 15 mg/kg of glycyrrhizic acid) also showed a synergistic anticancer effect. Meanwhile, inflammatory factors and pathological examination of the colon showed that Cmb8 could alleviate the gastrointestinal damage induced by CPT-11. Metabolic profiling of the tumors suggested that the synergistic anticancer effect of Cmb8 might be related to the regulation of fatty acid metabolism.

Conclusion: The optimal combination of four components derived from HQD for the synergistic sensitization of CPT-11 against CRC was identified.

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黄芩煎剂中四种活性成分的最佳组合对伊立替康抗结直肠癌的协同增敏作用。

背景：伊立替康（CPT-11伊立替康（CPT-11）是晚期结直肠癌（CRC）的一线治疗药物。在我们之前的研究中，从黄芩煎剂（HQD）中提取的四种成分（黄芩苷、黄芩素、乌药苷和甘草酸）已被证实可增强 CPT-11 的抗癌活性：本研究旨在确定四种成分对 CPT-11 增敏的最佳组合，并探讨其潜在机制：方法：采用正交设计法获得四种成分的候选组合（Cmb1-9）。首先在体外通过细胞活力、伤口愈合能力、克隆形成、细胞凋亡和细胞周期停滞来评估不同组合对 CPT-11 抗癌效果的影响。然后，构建了一个 CRC 异种移植小鼠模型，以评估最佳组合的体内抗癌效果。通过靶向代谢组学分析了最佳组合与CPT-11联合对CRC产生增敏作用的潜在机制：体外实验结果表明，由黄芩苷、黄芩素、乌药苷和甘草酸组成的 Cmb8 是最有效的组合，其浓度分别为 17 μM、47 μM、46.5 μM 和 9.8 μM。重要的是，细胞活力测定显示，Cmb8 与 CPT-11 联用具有协同抗癌活性。在体内实验中，这种组合（15 毫克/千克黄芩苷、24 毫克/千克黄芩素、24 毫克/千克乌鸡素和 15 毫克/千克甘草酸）也显示出协同抗癌作用。同时，结肠的炎症因子和病理检查显示，Cmb8 可以减轻 CPT-11 引起的胃肠道损伤。肿瘤的代谢谱分析表明，Cmb8的协同抗癌作用可能与脂肪酸代谢的调节有关：结论：从HQD中提取的四种成分的最佳组合已被确定，可协同增敏CPT-11对CRC的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Chinese Medicine INTEGRATIVE & COMPLEMENTARY MEDICINE-PHARMACOLOGY & PHARMACY

CiteScore

7.90

自引率

4.10%

发文量

133

审稿时长

31 weeks

期刊介绍： Chinese Medicine is an open access, online journal publishing evidence-based, scientifically justified, and ethical research into all aspects of Chinese medicine. Areas of interest include recent advances in herbal medicine, clinical nutrition, clinical diagnosis, acupuncture, pharmaceutics, biomedical sciences, epidemiology, education, informatics, sociology, and psychology that are relevant and significant to Chinese medicine. Examples of research approaches include biomedical experimentation, high-throughput technology, clinical trials, systematic reviews, meta-analysis, sampled surveys, simulation, data curation, statistics, omics, translational medicine, and integrative methodologies. Chinese Medicine is a credible channel to communicate unbiased scientific data, information, and knowledge in Chinese medicine among researchers, clinicians, academics, and students in Chinese medicine and other scientific disciplines of medicine.