Rastinpour Zeinab, Fakhri Sajad, Abbaszadeh Fatemeh, Ranjbari Mohammad, Kiani Amir, Namiq Amin Mohammed, 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 May 15;16:1589751. doi: 10.3389/fphar.2025.1589751. eCollection 2025.
Given the complexity of pathological mechanisms behind Alzheimer's disease (AD), there is a pressing need for novel multi-targeting therapeutic agents. Astaxanthin, a natural compound with diverse biological effects, has emerged as a potential candidate in neuronal diseases.
This study aimed to evaluate the neuroprotective effects of astaxanthin in a scopolamine-induced rat model of AD.
In total, 36 male Wistar rats were divided into six groups, including a control group receiving normal saline, a negative control group treated with scopolamine (1 mg/kg), and two groups receiving astaxanthin at doses of 5 and 10 mg/kg. Additionally, two groups were pre-treated with naloxone (0.1 mg/kg) or flumazenil (0.5 mg/kg) to block opioid and benzodiazepine receptors, respectively, followed by receiving the most effective dose of astaxanthin (i.e., 10 mg/kg). Treatments were administered via intraperitoneal injection for 14 consecutive days and behavioral tests were done. Biochemical analyses, zymography, Western blotting, and histopathological examinations were also performed.
Astaxanthin treatment significantly improved cognitive function, enhanced plasma antioxidant capacity by increasing catalase and glutathione levels, and reduced nitrite levels. It also increased serum activity of matrix metalloproteinase 2 (MMP-2), while decreasing MMP-9, increasing the expression of nuclear factor erythroid 2-related factor 2 (Nrf-2) and decreasing nuclear factor kappa B (NF-κB) in hippocampal tissue. Histopathological findings indicated reduced hippocampal damage after astaxanthin administration. The aforementioned protective effects of astaxanthin were reversed by naloxone and flumazenil.
Astaxanthin demonstrates protective effects against scopolamine-induced AD through its neuroprotective, antioxidant, and anti-inflammatory properties, potentially involving interactions with opioid and benzodiazepine receptors.
鉴于阿尔茨海默病（AD）背后病理机制的复杂性，迫切需要新型多靶点治疗药物。虾青素是一种具有多种生物学效应的天然化合物，已成为神经疾病的潜在候选药物。
本研究旨在评估虾青素在东莨菪碱诱导的AD大鼠模型中的神经保护作用。
总共36只雄性Wistar大鼠被分为六组，包括接受生理盐水的对照组、用东莨菪碱（1mg/kg）治疗的阴性对照组，以及接受5mg/kg和10mg/kg剂量虾青素的两组。此外，两组分别用纳洛酮（0.1mg/kg）或氟马西尼（0.5mg/kg）预处理以分别阻断阿片类和苯二氮䓬类受体，然后接受最有效剂量的虾青素（即10mg/kg）。通过腹腔注射连续给药14天并进行行为测试。还进行了生化分析、酶谱分析、蛋白质免疫印迹分析和组织病理学检查。
虾青素治疗显著改善了认知功能，通过增加过氧化氢酶和谷胱甘肽水平提高了血浆抗氧化能力，并降低了亚硝酸盐水平。它还增加了基质金属蛋白酶2（MMP-2）的血清活性，同时降低了MMP-9，增加了海马组织中核因子红细胞2相关因子2（Nrf-2）的表达并降低了核因子κB（NF-κB）。组织病理学结果表明虾青素给药后海马损伤减轻。纳洛酮和氟马西尼逆转了虾青素的上述保护作用。
虾青素通过其神经保护、抗氧化和抗炎特性对东莨菪碱诱导的AD具有保护作用，可能涉及与阿片类和苯二氮䓬类受体的相互作用。
