Residential College | false |
Status | 已發表Published |
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 Publication | European Journal of Pharmacology
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ISSN | 0014-2999 |
Volume | 918 |
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. |
Keyword | Bile Acid (Ba) Colorectal Cancer (Crc) Farnesoid x Receptor (Fxr) Gut Microbiota (Gm) Kaempferol |
DOI | 10.1016/j.ejphar.2022.174773 |
URL | View the original |
Indexed By | SCIE |
Language | 英語English |
WOS Research Area | Pharmacology & Pharmacy |
WOS Subject | Pharmacology & Pharmacy |
WOS ID | WOS:000754708600004 |
Scopus ID | 2-s2.0-85123612901 |
Fulltext Access | |
Citation statistics | |
Document Type | Journal article |
Collection | University of Macau |
Corresponding Author | Liu, Zhongqiu |
Affiliation | 1.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 Affilication | University 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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