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Kaempferol acts on bile acid signaling and gut microbiota to attenuate the tumor burden in ApcMin/+ mice
Li, Xiaoyan1,3; Khan, Imran2; Huang, Guoxin2; Lu, Yiyan1; Wang, Liping1; Liu, Yuanyuan1; Lu, Linlin1; Hsiao, W. L.Wendy2; Liu, Zhongqiu1,2
2022-03-05
Source PublicationEuropean Journal of Pharmacology
ISSN0014-2999
Volume918
Abstract

Emerging evidence points to a strong association between the bile acid (BA)-gut microbiota (GM) axis, and the risk of colorectal cancer (CRC). Kaempferol, a common polyphenol in the daily diet, shows various pharmacological activities. However, it remains unclear about the effect of kaempferol on the CRC development and the BA-GM homeostasis. Here, we found kaempferol effectively reduced tumor burden, restored the damaged intestinal barrier and downregulated antigen Ki67 and leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) expressions in Apc mice. For BA metabolism, kaempferol reversed the decreasing trend in chenodesoxycholic acid (CDCA) and 12α-hydroxylated BAs by increasing the sterol 27-hydroxylase (CYP27A1) and sterol 12α-hydroxylase (CYP8B1) expressions, and upregulated FXR expression. Importantly, molecular docking analysis revealed a direct interaction between kaempferol and farnesoid X receptor (FXR), the mater regulator of BA signaling. For GM analysis, we found higher abundances of species with anticancer properties and lower abundances of species associated with inflammation, obesity, and metabolic disorders in kaempferol-treated groups. Moreover, the gut of kaempferol-treated mice was predominantly colonized by short-chain fatty acid (SCFA) and lactic acid producing bacteria. Based on the PICRUSt-predicted pathways of our GM dataset, we demonstrated that kaempferol downregulated secondary BA synthesis pathways, increased G protein-coupled receptor activity and decreased NOD-like receptor activity, affecting cell differentiation, proliferation, survival, and apoptosis. Collectively, these results reveal that kaempferol effectively attenuates the tumor burden in Apc mice by modulating the BA signaling and GM homeostasis.

KeywordBile Acid (Ba) Colorectal Cancer (Crc) Farnesoid x Receptor (Fxr) Gut Microbiota (Gm) Kaempferol
DOI10.1016/j.ejphar.2022.174773
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaPharmacology & Pharmacy
WOS SubjectPharmacology & Pharmacy
WOS IDWOS:000754708600004
Scopus ID2-s2.0-85123612901
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Citation statistics
Document TypeJournal article
CollectionUniversity of Macau
Corresponding AuthorLiu, Zhongqiu
Affiliation1.International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China
2.State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, 999078, Macao
3.Department of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004, China
Corresponding Author AffilicationUniversity of Macau
Recommended Citation
GB/T 7714
Li, Xiaoyan,Khan, Imran,Huang, Guoxin,et al. Kaempferol acts on bile acid signaling and gut microbiota to attenuate the tumor burden in ApcMin/+ mice[J]. European Journal of Pharmacology, 2022, 918.
APA Li, Xiaoyan., Khan, Imran., Huang, Guoxin., Lu, Yiyan., Wang, Liping., Liu, Yuanyuan., Lu, Linlin., Hsiao, W. L.Wendy., & Liu, Zhongqiu (2022). Kaempferol acts on bile acid signaling and gut microbiota to attenuate the tumor burden in ApcMin/+ mice. European Journal of Pharmacology, 918.
MLA Li, Xiaoyan,et al."Kaempferol acts on bile acid signaling and gut microbiota to attenuate the tumor burden in ApcMin/+ mice".European Journal of Pharmacology 918(2022).
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