Baicalein, an enteric microbial metabolite, suppresses gut inflammation and cancer progression in ApcMin/+ mice
-
C.Z. Wang [1] ; C.F. Zhang [1] ; Y. Luo [1] ; H. Yao [1] ; C. Yu [1] ; L. Chen [1] ; J. Yuan [1] ; W.H. Huang [1] ; J.Y. Wan [1] ; J. Zeng [1] ; W. R. Sawadogo [1] ; C.S. Yuan [1]
-
[1] Tang Center for Herbal Medicine Research, Pritzker School of Medicine, University of Chicago, 5841 S. Maryland Ave., MC 4028, Chicago, IL 60637, USA
-
- Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 22, Nº. 7, 2020, págs. 1013-1022
- Idioma: inglés
- Texto completo no disponible (Saber más ...)
-
Resumen
ObjectiveChronic inflammation is recognized as a risk factor for colorectal cancer (CRC) development. Baicalin (BI), a major constituent in an anti-inflammatory herb Scutellaria baicalensis, can be biotransformed into baicalein (BE) by the intestinal microbiota. We evaluated the anti-inflammation and anti-CRC effects of the metabolite BE.MethodsThe in vitro biotransformation by human intestinal microbiota from BI into BE has been determined with HPLC. Using a gut-specific ApcMin/+ mouse model, the effects of oral BE on the life span, organ index, and tumor multiplicity were evaluated. The expressions of inflammatory cytokines were determined using ELISA. To verify the in vivo data, the anti-inflammatory and antiproliferative effects of BE were determined with an in vitro cell model.ResultsHPLC analysis showed that BI was quickly transformed into BE by the intestinal microbiota. Oral BE (30 mg/kg/day) significantly increased the life span, from 125.2 to 218.4 days (P < 0.01%). BE treatment also decreased intestine index and increased spleen index. Compared with the model group, following BE treatment, tumor numbers were significantly reduced in the small intestine and colon (P < 0.01, P < 0.05, respectively). In the gut tissues, BE treatment significantly reduced inflammatory cytokine levels such as IL-1β, IL-2, IL-6, IL-10, G-CSF, and GM-CSF. In vitro data supported our in vivo results that the anti-CRC effects of BE were via the inhibition of gut inflammation and induction of cancer cell death.Conclusion Our results suggest that the parent compound BI can be quickly converted into its microbial metabolite BE, which has stronger bioactive effects than BI. Baicalein is an active chemopreventive metabolite for inflammatory associated CRC.
