Next Article in Journal
The Allosteric Regulation of the DNA-Binding Domain of p53 by the Intrinsically Disordered C-Terminal Domain
Previous Article in Journal
Kinetics of MM1.S Multiple Myeloma Cells in a 3D Polymer Particle Culture System with Bone Marrow Stromal Cells and Bortezomib
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Pharmaceuticals
Volume 19
Issue 1
10.3390/ph19010123
pharmaceuticals-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Investigating the Protective Mechanisms of Ginseng-Natto Composite Fermentation Products in Alzheimer’s Disease: A Gut Microbiota and Metabolomic Approach

by
Zhimeng Li
1,
He Wang
1,
Huiyang Yuan
1,
Yue Zhang
2,
Bo Yang
1,
Guoxin Ji
1,
Zhuangzhuang Yao
1,
Mingfang Kuang
1,
Xian Wu
1,
Shumin Wang
1,* and
Huan Wang
1,3,*
1
College of Pharmacy, Changchun University of Chinese Medicine, Changchun 130117, China
2
Department of Scientific Research, Jilin Normal University, Siping 136000, China
3
Ginseng Scientific Research Institute, Changchun University of Chinese Medicine, Changchun 130117, China
*
Authors to whom correspondence should be addressed.
Pharmaceuticals 2026, 19(1), 123; https://doi.org/10.3390/ph19010123
Submission received: 4 December 2025 / Revised: 6 January 2026 / Accepted: 7 January 2026 / Published: 10 January 2026
(This article belongs to the Section Natural Products)
Browse Figures
Versions Notes

Abstract

Background: Alzheimer’s disease (AD), a progressive brain disorder, is the most common form of dementia and necessitates the development of effective intervention strategies. Ginseng-Natto composite fermentation products (GN) have demonstrated beneficial bioactivities in mouse models of AD; however, the underlying mechanism of action through which GN ameliorates AD requires further elucidation. Methods: Mice received daily intragastric administration of low- or high-dose GN for 4 weeks, followed by intraperitoneal injection of scopolamine to induce the AD model. The pharmacological effects of GN were systematically evaluated using the Morris water maze test, ELISA, and H&E staining. To further investigate the underlying mechanisms, 16S rRNA gene sequencing and metabolomics were employed to analyze the regulatory effects of GN on the gut–brain axis. Additionally, Western blotting was performed to assess the impact of GN on blood–brain barrier (BBB) integrity. Results: GN intervention significantly ameliorated cognitive deficits and attenuated neuropathological injury in AD mice, restoring the brain levels of acetylcholine (ACh), acetylcholinesterase (AChE), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) to normal ranges. GN reshaped the gut microbiota by promoting beneficial bacteria and inhibiting pro-inflammatory strains. It also regulated key metabolic pathways related to amino acid and unsaturated fatty acid metabolism. This metabolic remodeling restored the compromised BBB integrity by upregulating tight junction proteins (ZO-1, Occludin and Claudin-1). Conclusions: Our findings demonstrate that GN ameliorates AD through a gut-to-brain pathway, mediated by reshaping the microbiota-metabolite axis and repairing the BBB. Thus, GN may represent a promising intervention candidate for AD.
Keywords: Ginseng-Natto composite fermentation products; Alzheimer’s disease; gut microbiota; metabolites; gut–brain axis; blood–brain barrier Ginseng-Natto composite fermentation products; Alzheimer’s disease; gut microbiota; metabolites; gut–brain axis; blood–brain barrier
Graphical Abstract

Share and Cite

MDPI and ACS Style

Li, Z.; Wang, H.; Yuan, H.; Zhang, Y.; Yang, B.; Ji, G.; Yao, Z.; Kuang, M.; Wu, X.; Wang, S.; et al. Investigating the Protective Mechanisms of Ginseng-Natto Composite Fermentation Products in Alzheimer’s Disease: A Gut Microbiota and Metabolomic Approach. Pharmaceuticals 2026, 19, 123. https://doi.org/10.3390/ph19010123

AMA Style

Li Z, Wang H, Yuan H, Zhang Y, Yang B, Ji G, Yao Z, Kuang M, Wu X, Wang S, et al. Investigating the Protective Mechanisms of Ginseng-Natto Composite Fermentation Products in Alzheimer’s Disease: A Gut Microbiota and Metabolomic Approach. Pharmaceuticals. 2026; 19(1):123. https://doi.org/10.3390/ph19010123

Chicago/Turabian Style

Li, Zhimeng, He Wang, Huiyang Yuan, Yue Zhang, Bo Yang, Guoxin Ji, Zhuangzhuang Yao, Mingfang Kuang, Xian Wu, Shumin Wang, and et al. 2026. "Investigating the Protective Mechanisms of Ginseng-Natto Composite Fermentation Products in Alzheimer’s Disease: A Gut Microbiota and Metabolomic Approach" Pharmaceuticals 19, no. 1: 123. https://doi.org/10.3390/ph19010123

APA Style

Li, Z., Wang, H., Yuan, H., Zhang, Y., Yang, B., Ji, G., Yao, Z., Kuang, M., Wu, X., Wang, S., & Wang, H. (2026). Investigating the Protective Mechanisms of Ginseng-Natto Composite Fermentation Products in Alzheimer’s Disease: A Gut Microbiota and Metabolomic Approach. Pharmaceuticals, 19(1), 123. https://doi.org/10.3390/ph19010123

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop