Kai-xin-san improves cognitive impairment in D-gal and Aβ25-35 induced ad rats by regulating gut microbiota and reducing neuronal damage

Huijuan Wang; Lifen Zhou; Qin Zheng; Yonggui Song; Weihua Huang; Lin Yang; Yongchang Xiong; Zhinan Cai; Ying Chen; Jinbin Yuan

doi:10.1016/j.jep.2024.118161

Kai-xin-san improves cognitive impairment in D-gal and Aβ_25-35 induced ad rats by regulating gut microbiota and reducing neuronal damage

J Ethnopharmacol. 2024 Jul 15:329:118161. doi: 10.1016/j.jep.2024.118161. Epub 2024 Apr 9.

Authors

Affiliations

¹ Key Lab of Modern Preparations of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang, 330004, China.
² Laboratory Animal Science and Technology Development Center, Jiangxi University of Chinese Medicine, Nanchang, 330004, China.
³ Department of Clinical Pharmacology, Xiangya Hospital, Institute of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, and National Clinical Research Center for Geriatric Disorders, Central South University, Changsha, 410008, China.
⁴ Key Lab of Modern Preparations of Traditional Chinese Medicine, Jiangxi University of Chinese Medicine, Nanchang, 330004, China. Electronic address: kings2008@163.com.

PMID: 38599474
DOI: 10.1016/j.jep.2024.118161

Abstract

Ethnopharmacological relevance: Kai-Xin-San (KXS) is a classic herbal formula for the treatment and prevention of AD (Alzheimer's disease) with definite curative effect, but its mechanism, which involves multiple components, pathways, and targets, is not yet fully understood.

Aim of the study: To verify the effect of KXS on gut microbiota and explore its anti-AD mechanism related with gut microbiota.

Materials and methods: AD rat model was established and evaluated by intraperitoneal injection of D-gal and bilateral hippocampal CA1 injections of Aβ_25-35. The pharmacodynamics of KXS in vivo includes general behavior, Morris water maze test, ELISA, Nissl & HE staining and immunofluorescence. Systematic analysis of gut microbiota was conducted using 16S rRNA gene sequencing technology. The potential role of gut microbiota in the anti-AD effect of KXS was validated with fecal microbiota transplantation (FMT) experiments.

Results: KXS could significantly improve cognitive impairment, reduce neuronal damage and attenuate neuroinflammation and colonic inflammation in vivo in AD model rats. Nine differential intestinal bacteria associated with AD were screened, in which four bacteria (Lactobacillus murinus, Ligilactobacillus, Alloprevotella, Prevotellaceae_NK3B31_group) were very significant.

Conclusion: KXS can maintain the ecological balance of intestinal microbiota and exert its anti-AD effect by regulating the composition and proportion of gut microbiota in AD rats through the microbiota-gut-brain axis.

Keywords: Alzheimer's disease; Cognitive impairment; Fecal microbiota transplantation; Gut microbiota; Kai-xin-san.

MeSH terms

Alzheimer Disease* / chemically induced
Alzheimer Disease* / drug therapy
Amyloid beta-Peptides* / metabolism
Animals
Cognitive Dysfunction* / chemically induced
Cognitive Dysfunction* / drug therapy
Disease Models, Animal
Drugs, Chinese Herbal* / pharmacology
Fecal Microbiota Transplantation
Gastrointestinal Microbiome* / drug effects
Hippocampus / drug effects
Hippocampus / metabolism
Hippocampus / pathology
Male
Morris Water Maze Test / drug effects
Neurons* / drug effects
Peptide Fragments*
Rats
Rats, Sprague-Dawley*

Substances

Drugs, Chinese Herbal
Peptide Fragments
Amyloid beta-Peptides
amyloid beta-protein (25-35)
Kai-Xin-San