Hussein Sarah A, Tolba Mai F, Michel Haidy E, Albohy Amgad, Azab Samar S
Center for Drug Discovery Research and Development, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
Center for Drug Discovery Research and Development, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt.
Neurotoxicology. 2025 Mar;107:22-36. doi: 10.1016/j.neuro.2025.01.003. Epub 2025 Jan 22.
Doxorubicin (DOX)-induced chemobrain has been reported in several studies. Its main culprit is the induction of massive amounts of reactive oxygen species (ROS), hence triggering damage to brain tissues and thus leading to neuroinflammation. Biochanin A (BIO-A) is known to be an antioxidant, anti-inflammatory, and neuroprotective agent. An in silico study was designed to examine the potential neuroprotective effect of BIO-A. An in vivo study was used to evaluate the modulatory effect of BIO-A on cognitive impairment engendered by DOX. The insilico investigation proved the putative neuroprotective effect of BIO-A. In the in vivo study, BIO-A treatment counteracted DOX-induced memory deficits, as evidenced by improved spatial memory in rats compared to the DOX-only group. BIO-A also reversed DOX-triggered hippocampal neurodegeneration and neuroinflammation, supported by a significant decrease in tissue contents of NF-κB (p65) by 32 % and NLRP3 by 36 % versus the DOX-only group. BIO-A also abrogated DOX-induced neurodegneration, as evidenced by increasing SIRT1 content by 2-fold and BDNF content by 2-fold versus the DOX-only group in hippocampal tissues. In addition, BIO-A ameliorated DOX-augmented apoptosis in the hippocampus, as evidenced by lowering caspase-3 content in the hippocampus by 26 % versus the DOX-only group. Regarding tauopathy, BIO-A reversed DOX-increased tauopathy by 35 % versus the DOX-only group. The neuroprotectant miR-132 was increased by BIO-A in hippocampal tissues by 4-fold, contrary to the DOX-only group. Thus, BIO-A treatment modulated DOX-induced behavioral, histological, and molecular changes in the hippocampi of rats. Further studies are recommended to evaluate BIO-A in early clinical trials for the purpose of protection against chemobrain in cancer patients.
多项研究报道了阿霉素（DOX）诱导的化疗脑。其主要原因是诱导大量活性氧（ROS），从而引发脑组织损伤并导致神经炎症。已知生物活性成分A（BIO - A）是一种抗氧化、抗炎和神经保护剂。一项计算机模拟研究旨在检验BIO - A的潜在神经保护作用。一项体内研究用于评估BIO - A对DOX所致认知障碍的调节作用。计算机模拟研究证实了BIO - A假定的神经保护作用。在体内研究中，BIO - A治疗抵消了DOX诱导的记忆缺陷，与仅接受DOX治疗的组相比，大鼠的空间记忆得到改善证明了这一点。BIO - A还逆转了DOX引发的海马神经退行性变和神经炎症，与仅接受DOX治疗的组相比，组织中NF - κB（p65）含量显著降低32%，NLRP3含量显著降低36%，这支持了上述结论。BIO - A还消除了DOX诱导的神经退行性变，与仅接受DOX治疗的组相比，海马组织中SIRT1含量增加2倍，BDNF含量增加2倍证明了这一点。此外，BIO - A改善了DOX增强的海马细胞凋亡，与仅接受DOX治疗的组相比，海马中caspase - 3含量降低26%证明了这一点。关于tau蛋白病，与仅接受DOX治疗的组相比，BIO - A使DOX增加的tau蛋白病逆转了35%。BIO - A使海马组织中的神经保护因子miR - 132增加了4倍，这与仅接受DOX治疗的组相反。因此，BIO - A治疗调节了DOX诱导的大鼠海马行为、组织学和分子变化。建议进一步研究以评估BIO - A在早期临床试验中对癌症患者化疗脑的保护作用。
