Zarneshan Seyede Nazanin, Fakhri Sajad, Kiani Amir, Abbaszadeh Fatemeh, Hosseini Seyede Zahra, Mohammadi-Noori Ehsan, Echeverría Javier
Student Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Front Pharmacol. 2025 Apr 17;16:1574323. doi: 10.3389/fphar.2025.1574323. eCollection 2025.
Considering the complex pathophysiological mechanisms behind Alzheimer's disease (AD), a few drugs for managing related cognitive symptoms have been approved. The phytochemical resveratrol has shown promising anti-inflammatory and antioxidant effects in AD, but it has low bioavailability. Chemical modification of resveratrol to its glycosylated form, polydatin (PD), significantly increases its bioavailability and bioactivity.
The study aimed to investigate the therapeutic potential and mechanisms of action of PD against AD in rats.
AD was caused by an intraperitoneal (i.p.) administration of aluminum chloride (AlCl). Six groups of six rats each were defined as sham, negative control (AlCl), positive control (Donepezil), and treatments (PD 5, 10, and 20 mg/kg, i.p.). On days 7, 8, 14, and 15, the rats' behavioral changes were assessed by the open field, Y-maze test, passive avoidance test, and elevated plus maze tests. At the end of the study, the blood samples were collected to assess the levels of glutathione (GSH), catalase (CAT), and nitrite, as well as the activity of matrix metalloproteinases (MMPs). Furthermore, hippocampal brain tissue was removed and used for histological investigations.
The findings revealed that PD injections at three different doses (5, 10, and 20 mg/kg) improved cognitive and other behavioral impairments. Furthermore, PD improved the antioxidant capacity by increasing GSH and CAT while decreasing serum nitrite levels. PD showed anti-inflammatory effects by reducing the activity of inflammatory MMP-9, while elevating the activity of anti-inflammatory MMP-2. PD also modulated pathogenic changes in the hippocampal brain tissue.
PD alleviated cognitive and other behavioral impairments in AD rats by enhancing antioxidant defenses and reducing neuroinflammation.
鉴于阿尔茨海默病（AD）背后复杂的病理生理机制，已批准了几种用于管理相关认知症状的药物。植物化学物质白藜芦醇在AD中显示出有前景的抗炎和抗氧化作用，但其生物利用度较低。将白藜芦醇化学修饰为其糖基化形式白藜芦醇苷（PD），可显著提高其生物利用度和生物活性。
本研究旨在探讨PD对大鼠AD的治疗潜力及作用机制。
通过腹腔注射氯化铝（AlCl）诱导AD。将六组大鼠（每组六只）分别定义为假手术组、阴性对照组（AlCl）、阳性对照组（多奈哌齐）和治疗组（PD 5、10和20 mg/kg，腹腔注射）。在第7、8、14和15天，通过旷场试验、Y迷宫试验、被动回避试验和高架十字迷宫试验评估大鼠的行为变化。在研究结束时，采集血样以评估谷胱甘肽（GSH）、过氧化氢酶（CAT）和亚硝酸盐水平，以及基质金属蛋白酶（MMPs）的活性。此外，取出海马脑组织用于组织学研究。
研究结果显示，三种不同剂量（5、10和20 mg/kg）的PD注射可改善认知和其他行为障碍。此外，PD通过增加GSH和CAT同时降低血清亚硝酸盐水平来提高抗氧化能力。PD通过降低炎性MMP-9的活性，同时提高抗炎MMP-2的活性来发挥抗炎作用。PD还调节了海马脑组织中的病理变化。
PD通过增强抗氧化防御和减轻神经炎症，缓解了AD大鼠的认知和其他行为障碍。
