Ma Huifen, Yu Zhiyang, Qiao Qiong, Wang Wenpan, Li Zhonghua, Wang Pan, Song Junying, Zhang Xiaowei, Su Yunfang, Sun Yiran, Xie Zhishen, Zhang Zhenqiang
Collaborative Innovation Center of Prevention and Treatment of Major Diseases by Chinese and Western Medicine, Henan University of Chinese Medicine, Zhengzhou, Henan 450046, China.
Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, Henan 450046, China.
iScience. 2025 Jun 3;28(7):112817. doi: 10.1016/j.isci.2025.112817. eCollection 2025 Jul 18.
There has been increasing interest in the connection between AD, gut microbiota, and metabolites. Kai-Xin-San (KXS) has been commonly employed in ancient and modern Chinese clinical trials for the treatment of dementia; however, whether the protective effect of KXS in AD is related to the gut microbiota remains elusive. APP/PS1 mice were used as the model of AD. 43 key metabolites influenced by KXS were screened using untargeted metabolomics. At the genus level, Clostridium_IV, Eubacterium, Acetatifactor, etc., were identified to be impacted by KXS using 16S rRNA sequencing. Additionally, we identified 9 distinct intestinal floras at the genus level that were correlated with 13 pivotal differential metabolites related to cognitive impairment. KXS also inhibited the neuroinflammation, mostly via regulating the key metabolites. A potential relationship between gut microbiota, metabolites, and neuroinflammation is suggested as a protective mechanism of KXS in AD. These findings provide support for further development of KXS.
人们对阿尔茨海默病（AD）、肠道微生物群和代谢物之间的联系越来越感兴趣。开心散（KXS）在古代和现代中国临床试验中一直被广泛用于治疗痴呆症；然而，KXS对AD的保护作用是否与肠道微生物群有关仍不清楚。以APP/PS1小鼠作为AD模型。使用非靶向代谢组学筛选出43种受KXS影响的关键代谢物。在属水平上，利用16S rRNA测序确定KXS会影响IV型梭菌、真杆菌、乙酸杆菌等。此外，我们在属水平上鉴定出9种不同的肠道菌群，它们与13种与认知障碍相关的关键差异代谢物相关。KXS还主要通过调节关键代谢物来抑制神经炎症。肠道微生物群、代谢物和神经炎症之间的潜在关系被认为是KXS在AD中的一种保护机制。这些发现为KXS的进一步开发提供了支持。
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