The Effect of Fennel (Foeniculum vulgare) on the JAK/STAT Pathway and Intestinal Barrier Function

Abstract

Foeniculum vulgare (F. vulgare), commonly known as fennel, is a flowering plant species in the family Apiaceae. It is believed to be one of the world's oldest medicinal herbs and has been used for its reported anti‐inflammatory and antipathogenic properties. Anethole, a major component of F. vulgare, has also been shown to inhibit tumor necrosis factor (TNF)‐induced activation of nuclear factor kappa B (NF‐kB) and interleukin‐1β in rats both of which are parts of wide ranging inflammatory pathways. F. vulgare has also been used as a complementary and alternative treatment for intestinal bowel disease (IBD) in some countries. To investigate this alternative treatment and F. vulgare's anti‐inflammatory properties further, the Janus Kinase/Signal Transducers and Activators of Transcription (JAK/STAT) pathway, which is known to be active in many forms of IBD, was selected to be interrogated by growing colonic (T84) monolayers in vitro with F. vulgare oil extract before being challenged with interferon‐gamma (IFN‐γ). A dextran sodium sulfate (DSS) murine model that was given F. vulgare extract was also used to model ulcerative colitis.Barrier studies of T84 monolayers showed pretreatments with F. vulgare oil extract significant protected transepithelial electrical resistance (TEER) as compared to monolayers which only received vehicle treatments prior to IFN‐γ challenge (Fig. 1A, P<0.01). IFN‐γ has been shown to significantly decrease TEER in cells.? Furthermore, tight junction protein‐1 (TJTP‐1) and occludin (OCLD), both important tight junction proteins, showed increased RNA expression in F. vulgare treated monolayers (Fig. 1B–C, P<0.05). Levels of STAT1 mRNA and total STAT1 protein were similar between IFN‐γ treatments, regardless of F. vulgare treatment (Fig. 2A, P>0.05). However, F. vulgare did inhibit phosphorylation of STAT1, showing decreasing amounts of pSTAT1 with increasing amounts of F. vulgare in T84 monolayers (Fig. 2B, P<0.05). In the DSS‐murine studies, mice given F. vulgare treatments showed marked decreases in ulcer indices as compared to mice only given DSS (Fig. 3B, P<0.05). mRNA transcripts of STAT1 showed decreases in F. vulgare treated mice when compared to mice only given DSS (Data not shown). Both phosphorylated STAT1 and total STAT1 levels were decreased in F. vulgare treated mice as compared to mice only given DSS (Fig. 4, P<0.05). The results of the in vitro and in vivo experiments demonstrate F. vulgare's protective effects on gastrointestinal barrier integrity and overall macroscopic structure in the colon. We propose that F. vulgare inhibits phosphorylation of STAT1 in vitro and inhibits both phosphorylation and transcription of STAT1 in vivo.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.