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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Ethnopharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1483883
KaiXinSan-JiaWei ameliorates cognitive dysfunction in APP/PS1 mice by intervening in gut microbiota and its metabolites
Provisionally accepted- 1 Institute of Traditional Chinese Medicine, Xinjiang Medical University, Ürümqi, China
- 2 Hospital of Traditional Chinese Medicine Affiliated to Xinjiang Medical University, Urumqi, Xinjiang, China
- 3 Xinjiang Medical University, Ürümqi, Xinjiang Uyghur Region, China
Background: Alzheimer's disease (AD) is a degenerative disease of the central nervous system characterized by progressive cognitive impairment and memory loss. Chinese medicine's therapeutic effect on AD has become a promising treatment option in recent years, and the Chinese herbal compound Kai Xin San-JiaWei (KXSJW) is one of its representatives. This study employed a comprehensive approach, including 16S rRNA and Gaschromatography-mass spectrometry (GC-MS) analysis, to investigate the therapeutic efficacy and intrinsic mechanism of KXSJW on AD.Methods: 50 3-month-old APP swe /PS1 dE9 transgenic mice were randomly divided into 5 groups (n=10): model group (M), donepezil group (Don), KXSJW-low dose group (KJW-L), KXSJWmedium dose group (KJW-M), KXSJW-high dose group (KJW-H), Ten 3-month-old C57BL/6 J wild-type mice were randomly selected as the control group (C). The control and model groups were administered saline by gavage, the donepezil group was administered donepezil (0.92 mg/kg/d), and the KXSJW-low/medium/high dose group was administered KXSJW extract (0.9/1.8/3.6ml/kg/d); each group was treated once daily for 2 months. The study employed the Morris Water Maze (MWM) to evaluate learning and cognitive abilities. Pathological changes in colon tissue were assessed through hematoxylin and eosin (HE) staining. Analysis of gut microbiota was conducted using 16S rRNA sequencing, and gut microbial metabolite (short chain fatty acids, SCFAs) content was detected using GC-MS. Colonic tissue barrier integrity was examined through immunohistochemistry and western blot, while β-amyloid deposition in brain tissue was assessed. ELISA was used to measure serum intestinal peptide hormones (Glucagon, GHRP-Ghrelin).Results: KXSJW enhanced learning ability and memory, reduced amyloid deposition in the brain tissue of AD model mice. KXSJW was able to restore the balance of intestinal flora and regulate the concentration of intestinal flora metabolites, especially represented by Firmicutes and its major metabolite butyric acid. Meanwhile, KXSJW restored the intestinal barrier function and improved the release level of intestinal peptide hormones (Glucagon, GHRP-Ghrelin
Keywords: Kaixin San-JiaWei 1, Alzheimer's disease 2, 16S rRNA 3, SCFAs 4, microbial-gutbrain axis 5, Intestinal Barrier 6
Received: 20 Aug 2024; Accepted: 21 Jan 2025.
Copyright: © 2025 Mana, Chen and Yuan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Lulu Mana, Institute of Traditional Chinese Medicine, Xinjiang Medical University, Ürümqi, China
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