Ibrahim Fouad Ghadha, Mabrouk Mostafa, El-Sayed Sara A M, Abdelhameed Mohamed F, Rizk Maha Z, Beherei Hanan H
Department of Therapeutic Chemistry, Pharmaceutical and Drug Industries Research Institute, National Research Centre, 33 El-Bohouth St., Dokki, Cairo, 12622, Egypt.
Refractories, Ceramics and Building Materials Department, Advanced Materials, Technology and Mineral Resources Research Institute, National Research Centre, 33 El Bohouth St., Dokki, PO Box 12622, Cairo, Egypt.
Biometals. 2025 Feb;38(1):203-229. doi: 10.1007/s10534-024-00648-4. Epub 2024 Nov 14.
Berberine (BBN) is a naturally occurring alkaloid as a secondary metabolite in many plants and exhibits several benefits including neuroprotective activities. However, data on the neuromodulating potential of nanoformulated BBN are still lacking. In the present study, BBN loaded within iron oxide nanoparticles (BBN-IONP) were prepared and characterized by transmission electron microscopy FTIR, X-ray photoelectron spectroscopy particle-size distribution, zeta potential, and HPLC. The remyelinating neuroprotective potential of BBN-IONP relative to free BBN was evaluated against cuprizone (CPZ)-induced neurotoxicity (rats administered 0.2% CPZ powder (w/w) for five weeks). CPZ rats were treated with either free BBN or IONP-BBN (50 mg/kg/day, orally) for 14 days. Cognitive function was estimated using Y-maze. Biochemically, total antioxidant capacity lipid peroxides and reduced glutathione in the brain tissue, as well as, serum interferon-gamma levels were estimated. Moreover, the genetic expression contents of myelin basic protein Matrix metallopeptidase-9 Tumor necrosis factor-α (TNF-α), and S100β were measured. The histopathological patterns and immunohistochemical assessment of Glial Fibrillary Acidic Protein in both cerebral cortex and hippocampus CA1 regions were investigated. CPZ-rats treated with either free BBN or IONP-BBN demonstrated memory restoring, anti-oxidative, anti-inflammatory, anti-astrocytic, and remyelinating activities. Comparing free BBN with IONP-BBN revealed that the latter altered the neuromodulating activities of BBN, showing superior neuroprotective activities of IONP-BBN relative to BBN. In conclusion, both forms of BBN possess neuroprotective potential. However, the use of IONPs for brain delivery and the safety of these nano-based forms need further investigation.
黄连素（BBN）是一种天然存在的生物碱，作为许多植物中的次生代谢产物，具有多种益处，包括神经保护活性。然而，关于纳米制剂BBN神经调节潜力的数据仍然缺乏。在本研究中，制备了负载在氧化铁纳米颗粒中的BBN（BBN-IONP），并通过透射电子显微镜、傅里叶变换红外光谱、X射线光电子能谱、粒度分布、zeta电位和高效液相色谱进行了表征。相对于游离BBN，评估了BBN-IONP对铜离子螯合剂（CPZ）诱导的神经毒性（给予大鼠0.2% CPZ粉末（w/w）持续五周）的再髓鞘化神经保护潜力。CPZ大鼠用游离BBN或IONP-BBN（50 mg/kg/天，口服）治疗14天。使用Y迷宫评估认知功能。生化方面，估计了脑组织中的总抗氧化能力、脂质过氧化物和还原型谷胱甘肽，以及血清干扰素-γ水平。此外，还测量了髓鞘碱性蛋白、基质金属蛋白酶-9、肿瘤坏死因子-α（TNF-α）和S100β的基因表达含量。研究了大脑皮层和海马CA1区的组织病理学模式以及胶质纤维酸性蛋白的免疫组织化学评估。用游离BBN或IONP-BBN治疗的CPZ大鼠表现出记忆恢复、抗氧化、抗炎、抗星形细胞和再髓鞘化活性。将游离BBN与IONP-BBN进行比较发现，后者改变了BBN的神经调节活性，显示出IONP-BBN相对于BBN具有更强的神经保护活性。总之，两种形式的BBN都具有神经保护潜力。然而，使用IONP进行脑内递送以及这些纳米基形式的安全性需要进一步研究。
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