Poncirin and its metabolite ponciretin attenuate colitis in mice by inhibiting LPS binding on TLR4 of macrophages and correcting Th17/Treg imbalance

Publication date: 2 August 2016
Source:Journal of Ethnopharmacology, Volume 189
Author(s): Geum-Dan Kang, Dong-Hyun Kim
Ethnopharmacological relevanceThe fruit of Poncirus trifoliate, which contains poncirin as a main constituent, is frequently used in the traditional Chinese medicine for inflammation, asthma, and infection diseases.Aim of the studyTo examine anti-colitic effects of poncirin and ponciretin, a metabolite of poncirin by gut microbiota.Materials and methodsColitis was induced in mice by the intrarectal injection of 2,4,6-trinitrobenzenesulfonic acid (TNBS). Inflammatory markers were analyzed by enzyme-linked immunosorbent assay, immunoblotting, quantitative polymerase chain reaction, confocal microscopy, and flow cytometry. Peritoneal macrophages were isolated from mice stimulated with 4% thioglycolate.ResultsPoncirin was metabolized to ponciretin in vitro and in vivo by gut microbiota of mice. Orally administered poncirin and ponciretin suppressed TNBS-induced colitis in mice: these inhibited colon shortening, myeloperoxidase activity, NF-κB activation, and Th17 cell differentiation, but increased occludin, claudin-1, and ZO-1 expressions and Treg cell differentiation. Poncirin and ponciretin suppressed the differentiation of splenocytes into Th17 cells and expression of IL-17 and Foxp3 in vitro, as well as the activation of macrophages stimulated with lipopolysaccharide (LPS) by inhibiting the binding of LPS on TLR4 of macrophages. These increased the differentiation of splenocytes into Treg cells. The ant-inflammatory effect of ponciretin was superior to that of poncirin.ConclusionOrally administered poncirin is metabolized to ponciretin by gut microbiota and poncirin and ponciretin attenuates colitis by suppressing NF-κB activation through the inhibition of LPS binding on macrophages and correcting Th17/Treg cell imbalance.

Graphical abstract

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