College of Medicine, Jiaxing University, Jiaxing 314001, China; Graduate school, Jilin Institute of Chemical Technology, Jilin 132022, China.
College of Medicine, Jiaxing University, Jiaxing 314001, China.
Fitoterapia. 2024 Oct;178:106150. doi: 10.1016/j.fitote.2024.106150. Epub 2024 Jul 30.
Ganoderma lucidum (Curtis) P. Karst.(G. lucidum) is a kind of fungi, which also a traditional Chinese medicine used for "wisdom growth" in China. Triterpenoids from G. lucidum (GLTs) are one of the main active ingredients. Based on the strategy of early intervention on Alzheimer's disease (AD) and the inextricable association between disordered gut microbiota and metabolites with AD, this study aimed to explore the mechanisms of GLTs in the protection against AD via microbiota-gut-brain axis with the aid of network pharmacology. In this study, LC-MS/MS was used to identify the main active ingredients of GLTs. Network pharmacology was used to predict the potential target and validated with Caco-2 cell model. D-galactose was used to induce the slow-onset AD on rats. Metabolomics methods basing on GC-MS combined with 16S rRNA sequencing technology was used to carry out microbiota-gut-metabolomics analysis in order to reveal the potential mechanisms of GLTs in the protection of AD. As results, GLTs showed a protection against AD effect on rats by intervening administration. The mechanisms were inextricably linked to GLTs interference with the balance of gut microbiota and metabolites. The main fecal metabolites involved were short-chain fatty acids and aromatic amino acid metabolites.
灵芝（Curtis）P. Karst.（G. lucidum）是一种真菌，也是中国传统医学中用于“益智”的药物。灵芝中的三萜类化合物（GLTs）是其主要活性成分之一。基于阿尔茨海默病（AD）的早期干预策略和肠道微生物群与 AD 之间代谢物紊乱的不可分割的联系，本研究旨在借助网络药理学，通过微生物群-肠-脑轴，探索 GLTs 对 AD 的保护作用机制。在本研究中，采用 LC-MS/MS 鉴定 GLTs 的主要活性成分。网络药理学用于预测潜在靶点，并通过 Caco-2 细胞模型进行验证。使用半乳糖诱导大鼠缓慢发作 AD。基于 GC-MS 结合 16S rRNA 测序技术的代谢组学方法进行肠道微生物群-代谢组学分析，以揭示 GLTs 对 AD 保护作用的潜在机制。结果表明，GLTs 通过干预给药对大鼠 AD 有保护作用。其机制与 GLTs 干扰肠道微生物群和代谢物平衡密切相关。涉及的主要粪便代谢物为短链脂肪酸和芳香族氨基酸代谢物。
