The involvement of gut microbiota in the anti-tumor effect of carnosic acid via IL-17 suppression in colorectal cancer

Siyu Li; Hongxin Yang; Lanzhou Li; Wenqi Wang; Hor-Yue Tan; Yidi Qu; Di Wang

doi:10.1016/j.cbi.2022.110080

The involvement of gut microbiota in the anti-tumor effect of carnosic acid via IL-17 suppression in colorectal cancer

Chem Biol Interact. 2022 Sep 25:365:110080. doi: 10.1016/j.cbi.2022.110080. Epub 2022 Aug 1.

Authors

Siyu Li¹, Hongxin Yang², Lanzhou Li³, Wenqi Wang⁴, Hor-Yue Tan⁵, Yidi Qu⁶, Di Wang⁷

Affiliations

¹ School of Life Sciences, Jilin University, Changchun, 130012, China. Electronic address: lisiy20@mails.jlu.edu.cn.
² School of Life Sciences, Jilin University, Changchun, 130012, China. Electronic address: yhx20@mails.jlu.edu.cn.
³ Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun, 130118, China. Electronic address: lilanzhou@jlau.edu.cn.
⁴ School of Life Sciences, Jilin University, Changchun, 130012, China. Electronic address: wangwq18@mails.jlu.edu.cn.
⁵ Centre for Chinese Herbal Medicine Drug Development, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China. Electronic address: hyhtan@hkbu.edu.hk.
⁶ School of Life Sciences, Jilin University, Changchun, 130012, China. Electronic address: quyd19@mails.jlu.edu.cn.
⁷ School of Life Sciences, Jilin University, Changchun, 130012, China; Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, Jilin Agricultural University, Changchun, 130118, China. Electronic address: jluwangdi@jlu.edu.cn.

PMID: 35926579
DOI: 10.1016/j.cbi.2022.110080

Abstract

Colorectal cancer (CRC) is a malignant tumor that threatens human health worldwide. Disturbance of the gut microbiota caused by various external factors is one of the leading causes. Carnosic acid (CA) is a phenolic diterpene compound, mainly isolated from rosemary plants, with anti-inflammatory and anti-tumor properties. In this study, we aimed to investigate the role of CA in CRC development and its underlying mechanisms in B6/JGpt-Apc^em1Cin(min)/Gpt (Apc^Min/+) mice based on the analysis of gut microbiota, serum metabolomics, and tumor proteomics. Enzyme-linked immunosorbent assay (ELISA) and Western blot were performed to confirm the changes in cytokine and protein levels related to inflammation after CA administration. CA regulated the abundance of the gut microbiota, which further caused changes in the production of dl-lactic acid. CA suppressed the inflammatory response by reducing the levels of IL-1β, -6, and -17A. Overall, CA showed anti-CRC properties via modulation of gut microbiota and serum metabolites through NF-κB/STAT3 signaling to inhibit IL-17 expression in Apc^Min/+ mice. These results provide experimental evidence for the future treatment of CRC with CA.

Keywords: Carnosic acid; Colorectal cancer; Gut microbiota; Inflammation; Proteomics; Serum metabolomics.

MeSH terms

Abietanes / pharmacology
Abietanes / therapeutic use
Animals
Colorectal Neoplasms* / drug therapy
Colorectal Neoplasms* / metabolism
Gastrointestinal Microbiome*
Humans
Interleukin-17
Mice

Substances

Abietanes
Interleukin-17
salvin