Brazilin-rich extract from Sappan wood attenuates neuroinflammation through the restoration of the gut microbiota: improving cognitive function in mice with age-related Alzheimer’s disease

Sun, Quancheng1,#; Cui, Zhan1,#; Li, Jinbi1; Zhang, Qingfu1; Zheng, Jie2; Lu, Fuping1,*; Liu, Fufeng1,*

1Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education; Tianjin Key Laboratory of Industrial Microbiology; College of Biotechnology, Tianjin University of Science & Technology, Tianjin, China

2Department of Chemical, Biomolecular, and Corrosion Engineering; The University of Akron, Akron, OH, USA

*Correspondence to: Fufeng Liu, PhD, fufengliu@tust.edu.cn; Fuping Lu, PhD, lfp@tust.edu.cn.

#Both authors contributed equally to this work.

Abstract

Alzheimer’s disease is an age-related neurodegenerative disorder characterized by amyloid-β accumulation, which leads to memory impairment, neuroinflammation, and imbalance in the gut microbiota. Targeting neuroinflammation and correcting the imbalance in the gut microbiota may be promising strategies for treating age-related Alzheimer’s disease. Sappan wood, a traditional Chinese medicine known for its neuroprotective and anti-inflammatory properties, has not been extensively studied for its effects on cognitive function in age-related Alzheimer’s disease and neuroinflammation. In this study, we demonstrated that Sappan wood extract, brazilin, is nontoxic and reduces the degree of cytotoxicity induced by amyloid-β oligomers in PC12 cells. Sappan wood extract can alleviate cognitive deficits and protect hippocampal neurons in the mouse model of age-related Alzheimer’s disease by reducing neuroinflammation caused by amyloid-β42 oligomers. Furthermore, Sappan wood extract significantly reverses the imbalance in the gut microbiota caused by amyloid-β oligomers, enhancing resistance to inflammatory damage and age-related Alzheimer’s disease. Therefore, Sappan wood extract shows significant potential for combating age-related Alzheimer’s disease by improving cognitive impairment and inhibiting neuroinflammation through the modulation of the gut microbiota.

巴西苏木素恢复肠道微生物群减轻神经炎症：改善衰老相关的阿尔茨海默病小鼠的认知功能

摘要

阿尔茨海默病是一种与年龄相关的神经退行性疾病，以淀粉样蛋白-β积累为特征，导致记忆损伤、神经炎症和肠道微生物群失衡。针对神经炎症和纠正肠道微生物群失衡可能是治疗衰老相关的阿尔茨海默病的有效策略。苏木是一种传统中药，以其神经保护和抗炎特性而闻名，但其对衰老相关的阿尔茨海默病认知功能和神经炎症的影响尚未得到广泛研究。实验结果显示，苏木提取物巴西苏木素是无毒的，并能降低淀粉样β蛋白寡聚体在 PC12 细胞中诱导的细胞毒性。通过减少淀粉样蛋白-β42寡聚体引起的神经炎症，巴西苏木素可以减轻尔茨海默病模型小鼠认知障碍，并保护海马神经元；同时可纠正淀粉样β蛋白寡聚体导致的肠道微生物群失衡，增强对炎症损伤和阿尔茨海默病的抵抗力。由此认为，巴西苏木素在治疗衰老相关的阿尔茨海默病方面显示出潜力，作用途径涉及恢复肠道微生物群和抑制神经炎症。