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Front. Pharmacol. | doi: 10.3389/fphar.2019.01035

Xanthoceraside could ameliorate Alzheimer’s disease symptoms of rats by affecting the gut microbiota composition and modulating the endogenous metabolites levels

Hongxu Zhou1, Jingjie Tai1,  Haiyan Xu1, Xiumei Lu1* and  Da-li Meng1*
  • 1Shenyang Pharmaceutical University, China

Xanthoceraside (XAN) is a natural-derived compound with anti-Alzheimer activity from the husks of Xanthoceras sorbifolia. Although its therapeutic effect had been confirmed in previous studies, the mechanism was still unclear due to its poor solubility and low permeability. In this study, the pharmacological effect of XAN on Alzheimer’s disease (AD) was confirmed by behavior experiments and H&E staining observation. Fecal microbiota transplantation (FMT) experiment also replicatedthe therapeutic effects, which indicating the potential targets of XAN on gut microbiota. The sequencing of 16S rRNA genes in fecal samples demonstrated that XAN reversed gut microbiota dysbiosis in AD animals. XAN could change the relative abundances of several phyla and genus of bacterial, particularly the ratio of Firmicutes/Bacteroidetes. Among them, Clostridium IV, Desulfovibrio, Corynebacterium and Enterorhabdus, had been reported to be involved in the pathologic developments of AD and other central nervous system disease. In metabolomics study, a series of host endogenous metabolites were detected, including amino acids, lysophosphatidylcholine, dihydrosphingosine, phytosphingosine, inosine and hypoxanthine, which were all closely associated with the development of AD. Combined with the Spearman’s correlation analysis, it was confirmed that the increases of five bacterial strains and decreses of six bacterial strains were closely correlated with the increases of nine host metabolites and the decreases of another five host metabolites. Therefore, XAN can modulate the structure of gut microbiota in AD rats, the changes of gut microbiota were significantly correlated with endogenous metabolites, and symptom of AD was ultimately alleviated. Our findings suggest XAN may be a potential therapeutic drug for AD and the gut microbiota may be potential targeting territory of XAN via microbiome-gut-brain pathway.

Keywords: Alzheimer’s disease, Xanthoceraside, Gut Microbiota, 16S rRNA gene sequencing, Metabolomics

Received: 07 Nov 2018; Accepted: 14 Aug 2019.

Copyright: © 2019 Zhou, Tai, Xu, Lu and Meng. 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) and the copyright owner(s) 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:
Prof. Xiumei Lu, Shenyang Pharmaceutical University, Shenyang, China, lynn1975@163.com
Prof. Da-li Meng, Shenyang Pharmaceutical University, Shenyang, China, mengdl@163.com