El-Nashar Heba A S, Abbas Haidy, Zewail Mariam, Noureldin Mohamed H, Ali Mai M, Shamaa Marium M, Khattab Mohamed A, Ibrahim Nehal
Pharmacognosy Department, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt.
Department of Pharmaceutics, Faculty of Pharmacy, Damanhour University, Damanhour 22514, Egypt.
Pharmaceuticals (Basel). 2022 Sep 28;15(10):1202. doi: 10.3390/ph15101202.
The vast socio-economic impact of Alzheimer's disease (AD) has prompted the search for new neuroprotective agents with good tolerability and safety profile. With its outstanding role as antioxidant and anti-inflammatory, alongside its anti-acetylcholinesterase activity, the artichoke can be implemented in a multi-targeted approach in AD therapy. Moreover, artichoke agricultural wastes can represent according to the current United Nations Sustainable Development goals an opportunity to produce medicinally valuable phenolic-rich extracts. In this context, the UPLC-ESI-MS/MS phytochemical characterization of artichoke bracts extract revealed the presence of mono- and di-caffeoylquinic acids and apigenin, luteolin, and kaempferol -glycosides with remarkable total phenolics and flavonoids contents. A broad antioxidant spectrum was established in vitro. Artichoke-loaded, chitosan-coated, solid lipid nanoparticles (SLNs) were prepared and characterized for their size, zeta potential, morphology, entrapment efficiency, release, and ex vivo permeation and showed suitable colloidal characteristics, a controlled release profile, and promising ex vivo permeation, indicating possibly better physicochemical and biopharmaceutical parameters than free artichoke extract. The anti-Alzheimer potential of the extract and prepared SLNs was assessed in vivo in streptozotocin-induced sporadic Alzheimer mice. A great improvement in cognitive functions and spatial memory recovery, in addition to a marked reduction of the inflammatory biomarker TNF-α, β-amyloid, and tau protein levels, were observed. Significant neuroprotective efficacy in dentate Gyrus sub-regions was achieved in mice treated with free artichoke extract and to a significantly higher extent with artichoke-loaded SLNs. The results clarify the strong potential of artichoke bracts extract as a botanical anti-AD drug and will contribute to altering the future medicinal outlook of artichoke bracts previously regarded as agro-industrial waste.
阿尔茨海默病（AD）巨大的社会经济影响促使人们寻找具有良好耐受性和安全性的新型神经保护剂。洋蓟具有出色的抗氧化、抗炎作用，以及抗乙酰胆碱酯酶活性，可用于AD治疗的多靶点方法。此外，根据当前联合国可持续发展目标，洋蓟农业废弃物可成为生产具有药用价值的富含酚类提取物的机会。在此背景下，对洋蓟苞片提取物进行的超高效液相色谱-电喷雾串联质谱（UPLC-ESI-MS/MS）植物化学表征显示，存在单咖啡酰奎宁酸和二咖啡酰奎宁酸以及芹菜素、木犀草素和山奈酚糖苷，总酚和黄酮含量显著。在体外建立了广泛的抗氧化谱。制备了载有洋蓟的壳聚糖包衣固体脂质纳米粒（SLN），并对其大小、zeta电位、形态、包封率、释放、离体渗透进行了表征，结果显示其具有合适的胶体特性、可控的释放曲线和良好的离体渗透性能，表明其理化和生物药剂学参数可能优于游离洋蓟提取物。在链脲佐菌素诱导的散发性阿尔茨海默病小鼠体内评估了提取物和制备的SLN的抗阿尔茨海默病潜力。观察到认知功能和空间记忆恢复有很大改善，此外炎症生物标志物肿瘤坏死因子-α、β-淀粉样蛋白和tau蛋白水平显著降低。在用游离洋蓟提取物治疗的小鼠中，齿状回亚区域具有显著的神经保护作用，而在用载有洋蓟的SLN治疗的小鼠中，这种作用更为显著。结果阐明了洋蓟苞片提取物作为一种植物性抗AD药物的强大潜力，并将有助于改变洋蓟苞片以往被视为农业工业废弃物的未来药用前景。
