Orabi Mohamed A A, Khalil Heba M A, Abouelela Mohamed E, Zaafar Dalia, Ahmed Yasmine H, Naggar Reham A, Alyami Hamad S, Abdel-Sattar El-Shaymaa, Matsunami Katsuyoshi, Hamdan Dalia I
Department of Pharmacognosy, College of Pharmacy, Najran University, Najran 55461, Saudi Arabia.
Department of Veterinary Hygiene and Management, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt.
Pharmaceuticals (Basel). 2021 Dec 14;14(12):1305. doi: 10.3390/ph14121305.
Chemotherapeutic-related toxicity exacerbates the increasing death rate among cancer patients, necessitating greater efforts to find a speedy solution. An in vivo assessment of the protective effect of the leaves polar fraction of hydromethanolic extract against doxorubicin (Dox)-induced neurotoxicity was performed. Intriguingly, this fraction ameliorated Dox-induced cognitive dysfunction; reduced serum ROS and brain TNF-α levels, upregulated the brain nerve growth factor (NGF) levels, markedly reduced caspase-3 immunoexpression, and restored the histological architecture of the brain hippocampus. The in vivo study results were corroborated with a UPLC-ESI-MS/MS profiling that revealed the presence of a high percentage of the plant polyphenolics. Molecular modeling of several identified molecules in this fraction demonstrated a strong binding affinity of flavan-3-ol derivatives with TACE enzymes, in agreement with the experimental in vivo neuroprotective activity. In conclusion, the leaves polar fraction possesses neuroprotective activity that could have a promising role in ameliorating chemotherapeutic-induced side effects.
化疗相关毒性加剧了癌症患者死亡率的上升，因此需要付出更大努力来迅速找到解决方案。对水甲醇提取物的叶极性部分对阿霉素（Dox）诱导的神经毒性的保护作用进行了体内评估。有趣的是，该部分改善了Dox诱导的认知功能障碍；降低了血清活性氧（ROS）和脑肿瘤坏死因子-α（TNF-α）水平，上调了脑神经营养因子（NGF）水平，显著降低了半胱天冬酶-3免疫表达，并恢复了脑海马体的组织结构。体内研究结果得到了超高效液相色谱-电喷雾串联质谱（UPLC-ESI-MS/MS）分析的证实，该分析揭示了植物多酚类物质的高比例存在。对该部分中几种已鉴定分子的分子模拟表明，黄烷-3-醇衍生物与肿瘤坏死因子-α转换酶（TACE）具有很强的结合亲和力，这与体内实验的神经保护活性一致。总之，叶极性部分具有神经保护活性，在改善化疗引起的副作用方面可能具有重要作用。
