Huang He, Ke Chunlian, Zhang Dongdong, Wu Jiezhong, Zhang Peng
Department of General Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510630, China.
School of Life Sciences, Shihezi University, Shihezi, 832003, China.
Funct Integr Genomics. 2023 Mar 28;23(2):106. doi: 10.1007/s10142-023-01042-y.
Screening Chinese angelica (CHA) and Fructus aurantii (FRA) for ingredients with therapeutic effects on colorectal cancer (CRC) and discovering novel targets for the prevention or treatment of CRC.
TCMSP database as a starting point for the initial selection of ingredients and targets, we screened and validated the ingredients and targets of CHA and FRA using tools such as Autodock Vina, R 4.2.0, and GROMACS. To obtain the pharmacokinetic information of the active ingredients, we performed ADMET prediction and consulted a large number of works related to CRC cell lines for the discussion and validation of the results.
Molecular dynamics simulation results showed the complexes formed between these components and targets can exist in a very stable tertiary structure under the human environment, and their side effects can be ignored.
Our study successfully explains the effective mechanism of CHA and FRA for improving CRC while predicting the potential targets PPARG, AKT1, RXRA, and PPARA of CHA and FRA for CRC treatment, which provides a new foundation for investigating the novel compounds of TCMs and a new direction for subsequent CRC research.
筛选当归和枳壳中对结直肠癌（CRC）具有治疗作用的成分，并发现预防或治疗CRC的新靶点。
以中药系统药理学数据库与分析平台（TCMSP）数据库作为初步筛选成分和靶点的起点，我们使用诸如自动对接软件Vina、R 4.2.0和分子动力学软件GROMACS等工具对当归和枳壳的成分和靶点进行筛选和验证。为了获得活性成分的药代动力学信息，我们进行了药物代谢及药物动力学（ADMET）预测，并查阅了大量与CRC细胞系相关的文献以对结果进行讨论和验证。
分子动力学模拟结果表明，这些成分与靶点之间形成的复合物在人体环境下能够以非常稳定的三级结构存在，且其副作用可忽略不计。
我们的研究成功阐释了当归和枳壳改善CRC的作用机制，同时预测了当归和枳壳治疗CRC的潜在靶点过氧化物酶体增殖物激活受体γ（PPARG）、蛋白激酶B（AKT1）、维甲酸X受体α（RXRA）和过氧化物酶体增殖物激活受体α（PPARA），为研究中药新型化合物提供了新依据，也为后续CRC研究提供了新方向。
