Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, 510080, China.
Department of Anatomy, Histology and Developmental Biology, School of Basic Medical Sciences, Shenzhen University Health Science Centre, Shenzhen, 518060, China.
Sci Rep. 2019 Dec 20;9(1):19575. doi: 10.1038/s41598-019-56149-9.
Alzheimer's disease (AD) is a complex disorder influenced by both genetic and environmental components and has become a major public health issue throughout the world. Oxidative stress and inflammation play important roles in the evolution of those major pathological symptoms. Jatrorrhizine (JAT), a main component of a traditional Chinese herbal, coptidis rhizome, has been shown to have neuroprotective effects and we previously showed that it is also able to clear oxygen free radicals and reduce inflammatory responses. In this study, we demonstrated that JAT administration could alleviate the learning and memory deficits in AD. Furthermore, we also found that JAT treatment reduced the levels of Aβ plaques in the cortex and hippocampus of APP/PS1 double-transgenic mice. Other studies suggest that there are gut microbiome alterations in AD. In order to explore the underlying mechanisms between gut microbiota and AD, DNA sequencing for 16s rDNA V3-V4 was performed in fecal samples from APP/PS1 transgenic mice and C57BL/6 wild-type (WT) mice. Our results indicated that APP/PS1 mice showed less Operational Taxonomic Units (OTUs) abundance in gut microbiota than WT mice and with different composition. Furthermore, JAT treatment enriched OTUs abundance and alpha diversity in APP/PS1 mice compared to WT mice. High dose of JAT treatment altered the abundance of some specific gut microbiota such as the most predominant phylum Firmicutes and Bacteroidetes in APP/PS1 mice. In conclusion, APP/PS1 mice display gut dysbiosis, and JAT treatment not only improved the memory deficits, but also regulated the abundance of the microbiota. This may provide a therapeutic way to balance the gut dysbiosis in AD patients.
阿尔茨海默病（AD）是一种受遗传和环境因素共同影响的复杂疾病，已成为全球主要的公共卫生问题。氧化应激和炎症在这些主要病理症状的发展中起着重要作用。黄连碱（JAT）是传统中药黄连的主要成分之一，已被证明具有神经保护作用，我们之前的研究还表明它还能够清除氧自由基并减少炎症反应。在这项研究中，我们证明了 JAT 给药可以减轻 AD 的学习和记忆障碍。此外，我们还发现 JAT 治疗降低了 APP/PS1 双转基因小鼠大脑皮质和海马体中 Aβ斑块的水平。其他研究表明 AD 存在肠道微生物组改变。为了探索肠道微生物组与 AD 之间的潜在机制，对 APP/PS1 转基因小鼠和 C57BL/6 野生型（WT）小鼠的粪便样本进行了 16s rDNA V3-V4 的 DNA 测序。我们的结果表明，APP/PS1 小鼠的肠道微生物组中的操作分类单元（OTUs）丰度低于 WT 小鼠，且组成不同。此外，与 WT 小鼠相比，JAT 治疗增加了 APP/PS1 小鼠的 OTUs 丰度和α多样性。高剂量 JAT 治疗改变了 APP/PS1 小鼠中某些特定肠道微生物组的丰度，如厚壁菌门和拟杆菌门。总之，APP/PS1 小鼠表现出肠道菌群失调，JAT 治疗不仅改善了记忆障碍，还调节了菌群的丰度。这可能为平衡 AD 患者的肠道菌群失调提供一种治疗方法。
