Brusatol鸦胆子苦醇的作用机制及科研应用
2026-03-30 来源:本站 点击次数:60
Brusatol（鸦胆子苦醇，AbMole，M8710）是一种从植物鸦胆子（Brucea javanica）中分离得到的喹啉类天然化合物，能抑制细胞蛋白的从头合成，并在多种细胞和动物模型中展现出显著的生物学活性。
参考文献及鸣谢
[1] Xie, J.; Lai, Z.; Zheng, X.; et al. Apoptotic activities of brusatol in human non-small cell lung cancer cells: Involvement of ROS-mediated mitochondrial-dependent pathway and inhibition of Nrf2-mediated antioxidant response. Toxicology 2021, 451, 152680.
[2] Guo, S.; Zhang, J.; Wei, C.; et al. Anticancer effects of brusatol in nasopharyngeal carcinoma through suppression of the Akt/mTOR signaling pathway. Cancer chemotherapy and pharmacology 2020, 85 (6), 1097-1108.
[3] Jorge, J.; Magalhaes, N.; Alves, R.; et al. Antitumor Effect of Brusatol in Acute Lymphoblastic Leukemia Models Is Triggered by Reactive Oxygen Species Accumulation. Biomedicines 2022, 10 (9).
[4] Chen, Z.; He, B.; Zhao, J.; et al. Brusatol suppresses the growth of intrahepatic cholangiocarcinoma by PI3K/Akt pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology 2022, 104, 154323.
[5] Guo, N.; Zhang, Y.; Yuan, G.; et al. Pharmacokinetics and nephrotoxicity of cisplatin modulated by combination therapy with brusatol. Frontiers in pharmacology 2026, 17, 1708101.
[6] Huang, C. H.; Wang, F. T.; Chan, W. H. Role of caspase-3-cleaved/activated PAK2 in brusatol-triggered apoptosis of human lung cancer A549 cells. Toxicology research 2022, 11 (5), 791-803.
[7] Turpaev, K.; Krizhanovskii, C.; Wang, X.; et al. The protein synthesis inhibitor brusatol normalizes high-fat diet-induced glucose intolerance in male C57BL/6 mice: role of translation factor eIF5A hypusination. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2019, 33 (3), 3510-3522.
[8] Qi, S.; Li, D.; Deng, F.; et al. Brusatol modulates the Nrf2/GCLC pathway to enhance ferroptosis in the treatment of oral squamous cell carcinoma. European journal of pharmacology 2025, 1003, 177935.
[9] Sutiningsih, D.; Nurjazuli, N.; Nugroho, D.; et al. Larvicidal Activity of Brusatol Isolated from Brucea javanica (L) Merr on Culex quinquefasciatus. Iranian journal of public health 2019, 48 (4), 688-696.
[10] Guo, N.; Zhang, X.; Bu, F.; et al. Determination of brusatol in plasma and tissues by LC-MS method and its application to a pharmacokinetic and distribution study in mice. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 2017, 1053, 20-26.
细胞实验参考
细胞系：MDA-MB-468 cells
方法： HCECs were pretreated with 15 nM brusatol (Nrf2 inhibitor, Abmole, USA) or 10 µM ZnPP for 1 h prior to TQ treatment. Subsequently, the cells were stimulated with C. albicans conidia for 8 h (PCR) or 24 h
浓度： 15 nM
处理时间：1 h
参考文献：Cytokine. 2023 Dec;172:156375.
* 上述方法来自公开文献，仅供相同目的实验参考。如实验目的、材料、方法不同，请参考其他文献。
在细胞实验中，Brusatol（鸦胆子苦醇，AbMole，M8710）（CAS No.：14907-98-3）以剂量和时间依赖性方式抑制多种癌细胞系的增殖，包括非小细胞肺癌细胞A549、H1650、PC9和HCC827[1]，鼻咽癌细胞CNE-1、CNE-2、5-8F和6-10B[2]，急性淋巴细胞白血病（ALL）细胞系KOPN-8（B-ALL）、CEM和MOLT-4（T-ALL）[3]，胶质瘤细胞LN229和U251[4]。
Brusatol（鸦胆子苦醇）作用机制涉及多个通路，首先 Brusatol（鸦胆子苦醇，AbMole，M8710）可抑制核因子E2相关因子2（Nrf2）通路，从而削弱细胞的抗氧化能力，导致活性氧（ROS）显著积累[5]；Brusatol（鸦胆子苦醇，AbMole，M8710）（CAS No.：14907-98-3）还能诱导线粒体膜电位下降，激活Caspase-3/7/9及PARP切割，促进线粒体依赖性凋亡[6]；引起G0/G1或G2/M期细胞周期阻滞，伴随Cyclin B1、Cdc25c、Cdc2 p34和Cyclin D1等调控蛋白表达改变[3]；抑制PI3K/Akt/mTOR信号通路，表现为p-PI3K和p-AKT水平降低，并上调PTEN表达；同时Brusatol（鸦胆子苦醇）还能抑制上皮-间质转化（EMT），上调E-cadherin，下调N-cadherin和vimentin；此外，Brusatol还能促进铁死亡（Ferroptosis），并下调PLK1、SCD1及KLF4/NCK2轴等关键分子。
Brusatol（鸦胆子苦醇）作用机制涉及多个通路，首先 Brusatol（鸦胆子苦醇，AbMole，M8710）可抑制核因子E2相关因子2（Nrf2）通路，从而削弱细胞的抗氧化能力，导致活性氧（ROS）显著积累[5]；Brusatol（鸦胆子苦醇，AbMole，M8710）（CAS No.：14907-98-3）还能诱导线粒体膜电位下降，激活Caspase-3/7/9及PARP切割，促进线粒体依赖性凋亡[6]；引起G0/G1或G2/M期细胞周期阻滞，伴随Cyclin B1、Cdc25c、Cdc2 p34和Cyclin D1等调控蛋白表达改变[3]；抑制PI3K/Akt/mTOR信号通路，表现为p-PI3K和p-AKT水平降低，并上调PTEN表达；同时Brusatol（鸦胆子苦醇）还能抑制上皮-间质转化（EMT），上调E-cadherin，下调N-cadherin和vimentin；此外，Brusatol还能促进铁死亡（Ferroptosis），并下调PLK1、SCD1及KLF4/NCK2轴等关键分子。
在动物实验中，Brusatol（鸦胆子苦醇，AbMole，M8710）在C57BL/6小鼠（高脂饮食模型）中以2周疗程改善葡萄糖耐量和胰岛β细胞功能[7]；在裸鼠异种移植模型中，腹腔或尾静脉给药可显著抑制Cal-27（舌鳞癌）[8]、CNE-1（鼻咽癌）、Hucc-T1（ICC）、Bel7404（肝癌）及胶质瘤等肿瘤生长，常用剂量范围为1–5 mg/kg（如1 mg/kg隔日一次或2 mg/kg每日一次）；在斑马鱼幼虫模型中，BrusatolBrusatol（鸦胆子苦醇）的LC50为0.010 ± 0.122 ppm，LC90为0.654 ± 0.081 ppm，且高浓度下引起明显形态学损伤[9]；药代动力学研究显示，经尾静脉单次给药后，Brusatol在小鼠血浆中迅速清除，但在组织中分布广泛，尤其在部分组织中的浓度可比血浆高10倍以上[10]。
综上，Brusatol（鸦胆子苦醇，AbMole，M8710）通过多通路、多靶点机制在多种细胞系和啮齿类动物模型中表现出强效的抗增殖、促凋亡、抗迁移及调控细胞命运的作用，是当前肿瘤生物学研究中的重要工具化合物。参考文献及鸣谢
[1] Xie, J.; Lai, Z.; Zheng, X.; et al. Apoptotic activities of brusatol in human non-small cell lung cancer cells: Involvement of ROS-mediated mitochondrial-dependent pathway and inhibition of Nrf2-mediated antioxidant response. Toxicology 2021, 451, 152680.
[2] Guo, S.; Zhang, J.; Wei, C.; et al. Anticancer effects of brusatol in nasopharyngeal carcinoma through suppression of the Akt/mTOR signaling pathway. Cancer chemotherapy and pharmacology 2020, 85 (6), 1097-1108.
[3] Jorge, J.; Magalhaes, N.; Alves, R.; et al. Antitumor Effect of Brusatol in Acute Lymphoblastic Leukemia Models Is Triggered by Reactive Oxygen Species Accumulation. Biomedicines 2022, 10 (9).
[4] Chen, Z.; He, B.; Zhao, J.; et al. Brusatol suppresses the growth of intrahepatic cholangiocarcinoma by PI3K/Akt pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology 2022, 104, 154323.
[5] Guo, N.; Zhang, Y.; Yuan, G.; et al. Pharmacokinetics and nephrotoxicity of cisplatin modulated by combination therapy with brusatol. Frontiers in pharmacology 2026, 17, 1708101.
[6] Huang, C. H.; Wang, F. T.; Chan, W. H. Role of caspase-3-cleaved/activated PAK2 in brusatol-triggered apoptosis of human lung cancer A549 cells. Toxicology research 2022, 11 (5), 791-803.
[7] Turpaev, K.; Krizhanovskii, C.; Wang, X.; et al. The protein synthesis inhibitor brusatol normalizes high-fat diet-induced glucose intolerance in male C57BL/6 mice: role of translation factor eIF5A hypusination. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2019, 33 (3), 3510-3522.
[8] Qi, S.; Li, D.; Deng, F.; et al. Brusatol modulates the Nrf2/GCLC pathway to enhance ferroptosis in the treatment of oral squamous cell carcinoma. European journal of pharmacology 2025, 1003, 177935.
[9] Sutiningsih, D.; Nurjazuli, N.; Nugroho, D.; et al. Larvicidal Activity of Brusatol Isolated from Brucea javanica (L) Merr on Culex quinquefasciatus. Iranian journal of public health 2019, 48 (4), 688-696.
[10] Guo, N.; Zhang, X.; Bu, F.; et al. Determination of brusatol in plasma and tissues by LC-MS method and its application to a pharmacokinetic and distribution study in mice. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 2017, 1053, 20-26.
细胞实验参考
细胞系：MDA-MB-468 cells
方法： HCECs were pretreated with 15 nM brusatol (Nrf2 inhibitor, Abmole, USA) or 10 µM ZnPP for 1 h prior to TQ treatment. Subsequently, the cells were stimulated with C. albicans conidia for 8 h (PCR) or 24 h
浓度： 15 nM
处理时间：1 h
参考文献：Cytokine. 2023 Dec;172:156375.
* 上述方法来自公开文献，仅供相同目的实验参考。如实验目的、材料、方法不同，请参考其他文献。
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