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Research Article | Open Access | Just Accepted

Integration of gut microbiota and metabolomics analysis to unravel the neuroprotective effects of Hydroxy-α-sanshool on Alzheimer's Disease

Ruo-Lan Li1,2,5,#Wen-Wen Chen3,#Hong Zhang4Qi Liang1Ling-Yu Wang1Wei Peng1( )Chun-Jie Wu1,2( )

1 State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, P.R. China;

2 Institute of Innovation, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, P.R. China;

3 Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 611137, P.R. China.

4 Meishan hospital of TCM, Meishan Hospital Affiliated to Chengdu University of Traditional Chinese Medicine, Meishan 620010, P.R. China

5 Sichuan Cancer Hospital and Institute, School of Medicine, University of Electronic Science and Technology of China, Chengdu 611137, P.R. China.

# Both of them should be considered as first authors

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Abstract

Alzheimer's disease (AD) is a common neurodegenerative disease, and oxidative stress induced by Aβ deposition is the key cause of neuronal apoptosis in AD patient. Hydroxy-α-sanshool (HAS) is the predominant flavour substances in the pericarp of Zanthoxylum bungeanum Maxim. (Rutaceae family), which is a known condiment food and herbal medicine in China. We attempt to comprehensively elucidate the pathway and related mechanisms of HAS therapy on AD through in vivo and in vitro experiments. The results showed that HAS could inhibit cell apoptosis, suppress the reactive oxygen species (ROS), and increase the antioxidative enzymes in Aβ1-42 induced HT22 cells. In vivo, HAS attenuated the learning and memory impairment in senescence-accelerated mouse prone 8 (SAMP8) mice, and protected neuronal cells in hippocampus. Interestingly, the 16S rRNA gene sequencing results showed HAS could restore the richness and diversity of the intestinal microbiota, reduce the abundance of Lactobacillus, and increase the abundance of Bateroides and Parabacteroides. Moreover, the contents of 10 metabolites were significantly changed after HAS treatment, which was beneficial to treat AD. In conclusion, HAS could inhibit apoptosis in nerve cells by attenuating Aβ induced oxidative stress level, while it can also influence the metabolic pathways and affect the gut microbiota composition of AD mice.

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Food Science and Human Wellness
Cite this article:
Li R-L, Chen W-W, Zhang H, et al. Integration of gut microbiota and metabolomics analysis to unravel the neuroprotective effects of Hydroxy-α-sanshool on Alzheimer's Disease. Food Science and Human Wellness, 2024, https://doi.org/10.26599/FSHW.2024.9250214

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Received: 24 November 2023
Revised: 13 December 2023
Accepted: 28 March 2024
Available online: 17 July 2024

© Tsinghua University Press 2024

Reprints and Permission requests may be sought directly from editorial office.
Email: nanores@tup.tsinghua.edu.cn

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