Wu Xipei, Qiu Xiaojun, Wang Shirui, Zhang Nihui, An Lingzhuo, Song Peijie, Li Xia, Gao Wenyuan
Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Faculty of Medicine, Tianjin University, Weijin Road, 300072 Tianjin, China.
Tibet Qizheng Tibetan Medicine Co., Ltd., 2 Tibet Nyingchi Deji Road, Bayi District, 860000, Linzhi City, Tibet Autonomous Region, China.
J Ethnopharmacol. 2025 Feb 11;341:119323. doi: 10.1016/j.jep.2025.119323. Epub 2025 Jan 2.
Originally formulated to mitigate high-altitude sickness, Xinnaoxin capsules (XNX) are composed of three traditional Chinese medicines (Rhodiola rosea L., Lycium barbarum L. and Hippophae rhamnoides) with properties of anti-hypoxia, anti-fatigue, and anti-aging. Emerging evidence now suggests that XNX may also offer therapeutic benefits in Alzheimer's disease (AD), highlighting its potential significance in the development of novel AD treatments.
This study aims to investigate whether XNX improves AD-related behavioral and cognitive deficits by enhancing antioxidant defenses, reducing peripheral and neuroinflammation, and protecting neurons.
The AD mouse model was established using D-galactose and aluminum chloride. Spatial memory and anxiety-like behaviors were assessed via the Morris water maze and open field tests to evaluate the therapeutic effects of XNX. Biochemical markers in hippocampal tissue and serum were measured using ELISA kits, while serum chemical composition was analyzed by LC-MS. Histopathological changes and amyloid-β deposition in the hippocampus were examined through hematoxylin-eosin (HE) staining and immunofluorescence. Additionally, hippocampal expression of apoptotic proteins Bax and Caspase-3, anti-apoptotic protein Bcl-2, and synaptic proteins PSD-95 and Syn were assessed via Western blot.
Behavioral tests demonstrated that XNX significantly improved spatial learning and memory abilities, as well as reduced anxiety-like behaviors in AD mice. XNX also modulated inflammatory cytokines and oxidative stress markers in hippocampal tissue and serum, while reducing amyloid-β deposition. Further LC-MS analysis of serum revealed a marked upregulation of compounds such as adenosine following treatment, with key metabolic pathways affected, including linoleic acid metabolism and phenylalanine, tyrosine, and tryptophan biosynthesis. HE staining and immunofluorescence indicated that XNX ameliorated neuronal damage and decreased amyloid-β accumulation. Western blot analysis confirmed that XNX inhibited neuronal apoptosis and preserved synaptic proteins in the hippocampus.
XNX mitigates AD-induced behavioral and cognitive deficits by enhancing antioxidant defenses, reducing peripheral and neuroinflammation, and protecting neurons. Our findings provide valuable data and a theoretical foundation for the potential therapeutic application of XNX in AD treatment and its further development.
心脑欣胶囊（XNX）最初是为缓解高原病而研制，由三种中药（红景天、枸杞和沙棘）组成，具有抗缺氧、抗疲劳和抗衰老的特性。现在有新证据表明，XNX在阿尔茨海默病（AD）中可能也有治疗作用，凸显了其在新型AD治疗药物研发中的潜在重要性。
本研究旨在探讨XNX是否通过增强抗氧化防御、减轻外周和神经炎症以及保护神经元来改善与AD相关的行为和认知缺陷。
使用D-半乳糖和氯化铝建立AD小鼠模型。通过Morris水迷宫和旷场试验评估空间记忆和焦虑样行为，以评价XNX的治疗效果。使用ELISA试剂盒检测海马组织和血清中的生化标志物，同时通过液相色谱-质谱联用（LC-MS）分析血清化学成分。通过苏木精-伊红（HE）染色和免疫荧光检查海马中的组织病理学变化和淀粉样β蛋白沉积。此外，通过蛋白质免疫印迹法评估海马中凋亡蛋白Bax和Caspase-3、抗凋亡蛋白Bcl-2以及突触蛋白PSD-95和Syn的表达。
行为测试表明，XNX显著改善了AD小鼠的空间学习和记忆能力，并减少了焦虑样行为。XNX还调节了海马组织和血清中的炎性细胞因子和氧化应激标志物，同时减少了淀粉样β蛋白沉积。血清的进一步LC-MS分析显示，治疗后腺苷等化合物显著上调，包括亚油酸代谢以及苯丙氨酸、酪氨酸和色氨酸生物合成在内的关键代谢途径受到影响。HE染色和免疫荧光表明，XNX改善了神经元损伤并减少了淀粉样β蛋白积累。蛋白质免疫印迹分析证实，XNX抑制了神经元凋亡并保留了海马中的突触蛋白。
XNX通过增强抗氧化防御、减轻外周和神经炎症以及保护神经元来减轻AD诱导的行为和认知缺陷。我们的研究结果为XNX在AD治疗中的潜在治疗应用及其进一步开发提供了有价值的数据和理论基础。
