Metabolome–microbiome insights into therapeutic impact of 8‐O‐acetylharpagide against breast cancer in a murine model

Author:

Qian Jiahui1,Zhao Xinyu1ORCID,Yuan Siyuan1,Su Sijia1ORCID,Chen Chang2ORCID,Gao Junfeng1,Tang Xu1,Men Siye1,Wen Binyu1ORCID

Affiliation:

1. Dongfang Hospital Beijing University of Chinese Medicine Beijing P. R. China

2. Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine, Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing P. R. China

Abstract

AbstractIridoid glycosides extract, which is the main active extract of Ajuga decumbens Thunb, has been proved to have anti‐breast cancer activity in previous studies. However, it is still unknown whether 8‐O‐acetylharpagide, a main active compound in the extract, has anti‐breast cancer activity. In this study, 4 T1 breast cancer mice model was first successfully established. Then the anti‐breast cancer effect of 8‐O‐acetylharpagide was systematically investigated. Feces were collected for metabolomics and 16S rRNA analysis to assess the potential mechanism. The results showed that 8‐O‐acetylharpagide was effective in reducing 4 T1 mouse tumor volume and weight compared with the model group. Metabolome analysis revealed 12 potential metabolite biomarkers in feces, mainly involved in primary bile acid biosynthesis and arachidonic acid metabolism. The 16S rRNA sequencing results demonstrated that 8‐O‐acetylharpagide modulated the abundance of the intestinal flora in 4 T1 mice. Spearman correlation analysis showed that calcitriol and prostaglandin G2 strongly correlated with Akkermansia, Firmicutes and Muribaculum. Overall, the active compound 8‐O‐acetylharpagide could inhibit significantly breast cancer growth in 4 T1 breast cancer model mice. The mechanism of the anti‐breast cancer effect of 8‐O‐acetylharpagide may be related to the regulation of primary bile acid biosynthesis and arachidonic acid metabolism and modulation of the abundance of Akkermansia and Firmicutes.

Publisher

Wiley

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