Metabolomic and microbial insights: Kai-Xin-San’s impact on Alzheimer’s disease pathology

Summary: 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 g...

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Main Authors: Huifen Ma, Zhiyang Yu, Qiong Qiao, Wenpan Wang, Zhonghua Li, Pan Wang, Junying Song, Xiaowei Zhang, Yunfang Su, Yiran Sun, Zhishen Xie, Zhenqiang Zhang
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:iScience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2589004225010788
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author Huifen Ma
Zhiyang Yu
Qiong Qiao
Wenpan Wang
Zhonghua Li
Pan Wang
Junying Song
Xiaowei Zhang
Yunfang Su
Yiran Sun
Zhishen Xie
Zhenqiang Zhang
author_facet Huifen Ma
Zhiyang Yu
Qiong Qiao
Wenpan Wang
Zhonghua Li
Pan Wang
Junying Song
Xiaowei Zhang
Yunfang Su
Yiran Sun
Zhishen Xie
Zhenqiang Zhang
author_sort Huifen Ma
collection DOAJ
description Summary: 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.
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spelling doaj-art-962d1a61d28b42478f4c18423bf2d2082025-08-20T03:21:51ZengElsevieriScience2589-00422025-07-0128711281710.1016/j.isci.2025.112817Metabolomic and microbial insights: Kai-Xin-San’s impact on Alzheimer’s disease pathologyHuifen Ma0Zhiyang Yu1Qiong Qiao2Wenpan Wang3Zhonghua Li4Pan Wang5Junying Song6Xiaowei Zhang7Yunfang Su8Yiran Sun9Zhishen Xie10Zhenqiang Zhang11Collaborative 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, ChinaAcademy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, Henan 450046, ChinaAcademy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, Henan 450046, ChinaAcademy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, Henan 450046, ChinaCollaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Zhengzhou, Henan 450046, China; Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, Henan 450046, ChinaCollaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Zhengzhou, Henan 450046, China; Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, Henan 450046, ChinaCollaborative 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, ChinaCollaborative 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, ChinaCollaborative 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, ChinaSchool of Pharmacy, Chengdu Medical College, Chengdu 610500, China; Corresponding authorCollaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Zhengzhou, Henan 450046, China; Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, Henan 450046, China; Corresponding authorCollaborative Innovation Center of Prevention and Treatment of Major Diseases by Chinese and Western Medicine, Henan University of Chinese Medicine, Zhengzhou, Henan 450046, China; Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Zhengzhou, Henan 450046, China; Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, Henan 450046, China; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004225010788Molecular neuroscienceMetabolomics
spellingShingle Huifen Ma
Zhiyang Yu
Qiong Qiao
Wenpan Wang
Zhonghua Li
Pan Wang
Junying Song
Xiaowei Zhang
Yunfang Su
Yiran Sun
Zhishen Xie
Zhenqiang Zhang
Metabolomic and microbial insights: Kai-Xin-San’s impact on Alzheimer’s disease pathology
iScience
Molecular neuroscience
Metabolomics
title Metabolomic and microbial insights: Kai-Xin-San’s impact on Alzheimer’s disease pathology
title_full Metabolomic and microbial insights: Kai-Xin-San’s impact on Alzheimer’s disease pathology
title_fullStr Metabolomic and microbial insights: Kai-Xin-San’s impact on Alzheimer’s disease pathology
title_full_unstemmed Metabolomic and microbial insights: Kai-Xin-San’s impact on Alzheimer’s disease pathology
title_short Metabolomic and microbial insights: Kai-Xin-San’s impact on Alzheimer’s disease pathology
title_sort metabolomic and microbial insights kai xin san s impact on alzheimer s disease pathology
topic Molecular neuroscience
Metabolomics
url http://www.sciencedirect.com/science/article/pii/S2589004225010788
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