Institute of Pharmaceutical & Food Engineering, Shanxi University of Chinese Medicine, Jinzhong, 030600, PR China; School of Pharmacy, Chengdu Medical College, Chengdu, 610500, PR China.
Institute of Pharmaceutical & Food Engineering, Shanxi University of Chinese Medicine, Jinzhong, 030600, PR China.
Eur J Pharmacol. 2022 Jan 5;914:174691. doi: 10.1016/j.ejphar.2021.174691. Epub 2021 Dec 8.
Hydroxy-α-sanshool (HAS) is an unsaturated fatty acid amide from Zanthoxylum bungeanum Maxim. with hypolipidemic, hypoglycemic, anti-inflammatory, and neurotrophic effects, etc. In this study, results indicated that HAS effectively ameliorated spontaneous locomotion deficit of mice induced by D-galactose (D-gal) and AlCl treatment in open field test. Results of Morris water maze test (MWM) showed that HAS significantly improved the spatial learning and memory ability of aging mice. Histopathological evaluations revealed that HAS markedly alleviated morphological changes and increased number of Nissl neurons in hippocampus of D-gal/AlCl-induced Alzheimer's disease (AD)-like mice. HAS markedly reduced malondialdehyde (MDA) production, and increased the activity of antioxidative enzymes including superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), showing an inhibitory effect on oxidative stress. Furthermore, HAS treatment obviously reversed the inhibitory expressions of mRNA and protein of HO-1 and Nrf2 in the hippocampus of AD mice, suggesting that neuroprotective effects of HAS against oxidative stress might be mediated by the Nrf2/HO-1 pathway. Meanwhile, HAS significantly inhibited neuronal apoptosis by decreasing mRNA and protein expressions of Cyt-c, Bax and Caspase 3, and increasing Bcl-2 expression in the hippocampus of AD mice. These results suggest that HAS have the potential to be developed as antioxidant drug for the prevention and early therapy of AD.
羟基-α-山椒素（HAS）是从花椒中提取的一种不饱和脂肪酸酰胺，具有降血脂、降血糖、抗炎和神经营养等作用。在这项研究中，结果表明 HAS 能有效改善 D-半乳糖（D-gal）和 AlCl 处理诱导的自发运动缺陷小鼠在旷场试验中的行为。Morris 水迷宫试验（MWM）的结果表明，HAS 显著改善了衰老小鼠的空间学习和记忆能力。组织病理学评价显示，HAS 明显减轻了 D-gal/AlCl 诱导的阿尔茨海默病（AD）样小鼠海马中的形态变化和尼氏神经元数量的增加。HAS 明显减少丙二醛（MDA）的产生，增加抗氧化酶包括超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）和过氧化氢酶（CAT）的活性，显示出对氧化应激的抑制作用。此外，HAS 处理明显逆转了 AD 小鼠海马中 HO-1 和 Nrf2 的 mRNA 和蛋白表达的抑制，表明 HAS 对氧化应激的神经保护作用可能是通过 Nrf2/HO-1 通路介导的。同时，HAS 通过降低 AD 小鼠海马中 Cyt-c、Bax 和 Caspase 3 的 mRNA 和蛋白表达，增加 Bcl-2 的表达，显著抑制神经元凋亡。这些结果表明，HAS 有可能作为预防和早期治疗 AD 的抗氧化药物进行开发。
