Zarneshan Seyede Nazanin, Arkan Elham, Kiani Amir, Hosseini Seyede Zahra, Abbaszadeh Fatemeh, Fakhri Sajad
Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jan 9. doi: 10.1007/s00210-024-03696-2.
Alzheimer's disease (AD) is the most frequent cause of dementia. Since there are complex pathophysiological mechanisms behind AD, and there is no effective treatment strategy, it is necessary to introduce novel multi-targeting agents with fewer side effects and higher efficacy. Polydatin (PD) is a naturally occurring resveratrol glucoside employing multiple mechanisms toward neuroprotection. In the current study, the anti-AD mechanisms of a novel amphiphilic chitosan nanocarrier formulation (ACN) of PD (NPD) were studied. After preparing the amphiphilic chitosan nanoformulation (i.e., NPD), physicochemical properties were assessed, including particle size, zeta potential, drug loading, drug release, MTT, Fourier transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM). For in vivo analysis, aluminum chloride (AlCl3) was injected intraperitoneally for 14 days to induce AD in male Albino Wistar rats. To examine the anti-AD mechanisms of NPD, a total of 36 rats were divided into six groups of six. Behavioral tests, including open field, Y-maze, elevated plus maze, and shuttle box were done on days 7, 8, 14, and 15. Additionally, zymography, biochemical analysis, and histological studies were done. NPD, as a newly synthesized formulation for PD, potentially improved memory and cognitive behavioral parameters and reduced the activity of inflammatory matrix metalloproteinase 9 (MMP9) and serum nitrite levels, while increasing anti-inflammatory MMP2, antioxidant catalase, and glutathione. NPD also prevented morphological changes and increased neuronal survival in the CA2, CA4, and DG regions of the rat hippocampus. In conclusion, NPD is a novel formulation against AD through anti-inflammatory, antioxidant, and neuroprotective mechanisms.
阿尔茨海默病（AD）是痴呆最常见的病因。由于AD背后存在复杂的病理生理机制，且尚无有效的治疗策略，因此有必要引入副作用更少、疗效更高的新型多靶点药物。白藜芦醇苷（PD）是一种天然存在的白藜芦醇糖苷，具有多种神经保护机制。在本研究中，对PD的新型两亲性壳聚糖纳米载体制剂（ACN）（即NPD）的抗AD机制进行了研究。制备两亲性壳聚糖纳米制剂（即NPD）后，评估了其理化性质，包括粒径、zeta电位、载药量、药物释放、MTT、傅里叶变换红外光谱（FT-IR）和扫描电子显微镜（SEM）。对于体内分析，腹腔注射氯化铝（AlCl3）14天以诱导雄性白化Wistar大鼠患AD。为了研究NPD的抗AD机制，将总共36只大鼠分为6组，每组6只。在第7、8、14和15天进行了行为测试，包括旷场试验、Y迷宫试验、高架十字迷宫试验和穿梭箱试验。此外，还进行了酶谱分析、生化分析和组织学研究。NPD作为一种新合成的PD制剂，可能改善记忆和认知行为参数，降低炎性基质金属蛋白酶9（MMP9）的活性和血清亚硝酸盐水平，同时增加抗炎性MMP2、抗氧化酶过氧化氢酶和谷胱甘肽。NPD还可防止大鼠海马CA2、CA4和齿状回区域的形态学变化并增加神经元存活。总之，NPD是一种通过抗炎、抗氧化和神经保护机制抗AD的新型制剂。
