Brusatol鴉膽子苦醇的作用機(jī)制及科研應(yīng)用
Brusatol（鴉膽子苦醇，AbMole，M8710）是一種從植物鴉膽子（Brucea javanica）中分離得到的喹啉類天然化合物，能抑制細(xì)胞蛋白的從頭合成，并在多種細(xì)胞和動物模型中展現(xiàn)出顯著的生物學(xué)活性。
參考文獻(xiàn)及鳴謝
[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.
細(xì)胞實驗參考
細(xì)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
濃度： 15 nM
處理時間：1 h
參考文獻(xiàn)：Cytokine. 2023 Dec;172:156375.
* 上述方法來自公開文獻(xiàn)，僅供相同目的實驗參考。如實驗?zāi)康摹⒉牧�、方法不同，請參考其他文獻(xiàn)。
在細(xì)胞實驗中，Brusatol（鴉膽子苦醇，AbMole，M8710）（CAS No.：14907-98-3）以劑量和時間依賴性方式抑制多種癌細(xì)胞系的增殖，包括非小細(xì)胞肺癌細(xì)胞A549、H1650、PC9和HCC827[1]，鼻咽癌細(xì)胞CNE-1、CNE-2、5-8F和6-10B[2]，急性淋巴細(xì)胞白血�。ˋLL）細(xì)胞系KOPN-8（B-ALL）、CEM和MOLT-4（T-ALL）[3]，膠質(zhì)瘤細(xì)胞LN229和U251[4]。
Brusatol（鴉膽子苦醇）作用機(jī)制涉及多個通路，首先 Brusatol（鴉膽子苦醇，AbMole，M8710）可抑制核因子E2相關(guān)因子2（Nrf2）通路，從而削弱細(xì)胞的抗氧化能力，導(dǎo)致活性氧（ROS）顯著積累[5]；Brusatol（鴉膽子苦醇，AbMole，M8710）（CAS No.：14907-98-3）還能誘導(dǎo)線粒體膜電位下降，激活Caspase-3/7/9及PARP切割，促進(jìn)線粒體依賴性凋亡[6]；引起G0/G1或G2/M期細(xì)胞周期阻滯，伴隨Cyclin B1、Cdc25c、Cdc2 p34和Cyclin D1等調(diào)控蛋白表達(dá)改變[3]；抑制PI3K/Akt/mTOR信號通路，表現(xiàn)為p-PI3K和p-AKT水平降低，并上調(diào)PTEN表達(dá)；同時Brusatol（鴉膽子苦醇）還能抑制上皮-間質(zhì)轉(zhuǎn)化（EMT），上調(diào)E-cadherin，下調(diào)N-cadherin和vimentin；此外，Brusatol還能促進(jìn)鐵死亡（Ferroptosis），并下調(diào)PLK1、SCD1及KLF4/NCK2軸等關(guān)鍵分子。
Brusatol（鴉膽子苦醇）作用機(jī)制涉及多個通路，首先 Brusatol（鴉膽子苦醇，AbMole，M8710）可抑制核因子E2相關(guān)因子2（Nrf2）通路，從而削弱細(xì)胞的抗氧化能力，導(dǎo)致活性氧（ROS）顯著積累[5]；Brusatol（鴉膽子苦醇，AbMole，M8710）（CAS No.：14907-98-3）還能誘導(dǎo)線粒體膜電位下降，激活Caspase-3/7/9及PARP切割，促進(jìn)線粒體依賴性凋亡[6]；引起G0/G1或G2/M期細(xì)胞周期阻滯，伴隨Cyclin B1、Cdc25c、Cdc2 p34和Cyclin D1等調(diào)控蛋白表達(dá)改變[3]；抑制PI3K/Akt/mTOR信號通路，表現(xiàn)為p-PI3K和p-AKT水平降低，并上調(diào)PTEN表達(dá)；同時Brusatol（鴉膽子苦醇）還能抑制上皮-間質(zhì)轉(zhuǎn)化（EMT），上調(diào)E-cadherin，下調(diào)N-cadherin和vimentin；此外，Brusatol還能促進(jìn)鐵死亡（Ferroptosis），并下調(diào)PLK1、SCD1及KLF4/NCK2軸等關(guān)鍵分子。
在動物實驗中，Brusatol（鴉膽子苦醇，AbMole，M8710）在C57BL/6小鼠（高脂飲食模型）中以2周療程改善葡萄糖耐量和胰島β細(xì)胞功能[7]；在裸鼠異種移植模型中，腹腔或尾靜脈給藥可顯著抑制Cal-27（舌鱗癌）[8]、CNE-1（鼻咽癌）、Hucc-T1（ICC）、Bel7404（肝癌）及膠質(zhì)瘤等腫瘤生長，常用劑量范圍為1–5 mg/kg（如1 mg/kg隔日一次或2 mg/kg每日一次）；在斑馬魚幼蟲模型中，BrusatolBrusatol（鴉膽子苦醇）的LC50為0.010 ± 0.122 ppm，LC90為0.654 ± 0.081 ppm，且高濃度下引起明顯形態(tài)學(xué)損傷[9]；藥代動力學(xué)研究顯示，經(jīng)尾靜脈單次給藥后，Brusatol在小鼠血漿中迅速清除，但在組織中分布廣泛，尤其在部分組織中的濃度可比血漿高10倍以上[10]。
綜上，Brusatol（鴉膽子苦醇，AbMole，M8710）通過多通路、多靶點機(jī)制在多種細(xì)胞系和嚙齒類動物模型中表現(xiàn)出強(qiáng)效的抗增殖、促凋亡、抗遷移及調(diào)控細(xì)胞命運的作用，是當(dāng)前腫瘤生物學(xué)研究中的重要工具化合物。參考文獻(xiàn)及鳴謝
[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.
細(xì)胞實驗參考
細(xì)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
濃度： 15 nM
處理時間：1 h
參考文獻(xiàn)：Cytokine. 2023 Dec;172:156375.
* 上述方法來自公開文獻(xiàn)，僅供相同目的實驗參考。如實驗?zāi)康摹⒉牧�、方法不同，請參考其他文獻(xiàn)。
- CRM197白喉毒素?zé)o毒突變體作為載體蛋白在疫苗中的應(yīng)用及臨床表現(xiàn)
- 線粒體超氧化物指示劑的原理及實驗應(yīng)用技術(shù)詳解
- 細(xì)胞因子的分子特征、作用機(jī)制及其在疾病研究中的臨床價值
- 趨化因子超家族及其受體的分子特征、分類、信號機(jī)制與生物學(xué)功能
- MTT細(xì)胞增殖及細(xì)胞毒性檢測法的原理、應(yīng)用及實驗標(biāo)準(zhǔn)操作流程全解析
- MTS檢測試劑盒的檢測原理、優(yōu)勢及在生物醫(yī)學(xué)研究中的應(yīng)用
- 細(xì)胞轉(zhuǎn)染效率優(yōu)化指南：從質(zhì)粒比例到收獲時間五大關(guān)鍵要素解析
- Biolaminin 521 CTG細(xì)胞治療級別培養(yǎng)基質(zhì)在干細(xì)胞培養(yǎng)中應(yīng)用技術(shù)解析
Copyright(C) 1998-2026 生物器材網(wǎng) 電話：021-64166852;13621656896 E-mail：info@bio-equip.com