6-(methylsulfinyl)hexyl isothiocyanate (6-MITC) from Wasabia japonica alleviates inflammatory bowel disease (IBD) by potential inhibition of glycogen synthase kinase 3 beta (GSK-3β)

Inflammatory bowel disease (IBD) describes a set of disorders involving alterations to gastrointestinal physiology and mucosal immunity. Unravelling its complex pathophysiology is important since many IBD patients are refractory or suffer adverse side effects from current treatments. Isothiocyanates (ITCs), such as 6-(methylsulfinyl)hexyl ITC (6-MITC) in Wasabia japonica, have potential anti-inflammatory activity. We aimed elucidate the pathways through which 6-MITC alleviates inflammation by examining role nuclear factor-kappa B (NF-κB) pathway inhibition glycogen synthase kinase 3 beta (GSK-3β) using chemically induced murine model IBD, cell-based silico techniques. The two NF-κB inhibitors, sulfasalazine (SS), pyrrolidine dithiolcarbamate (PDTC) were investigated on dextran sulfate sodium (DSS)-induced mouse acute chronic colitis macroscopic measurements pro-inflammatory markers. effect induction was assessed macrophage cell line. Complexes GSK-3β-6-MITC GSK-3β-ATP generated mechanism 6-MITC’s direct GSK-3β. Changes markers, inducible nitric oxide (iNOS) (increased) interleukin-6 (IL-6) (decreased) demonstrated that iNOS regulation occurred at translational level. Intraperitoneal (ip) injection colitis-induced mice ameliorated weight loss whereas oral administration had negligible effect. Fecal blood colon weight/length ratio parameters improved treatment with other inhibitors. Levels decreased upon addition vitro while structural studies showed acts competitively inhibit GSK-3β ATP binding site. In this study we inhibits signaling via ameliorating fecal blood, colonic DSS-induced indirectly indicating reduced intestinal stress. Taken together these results suggest for acting alleviate GSK-3β/NF-κB pathway. Furthermore, can be utilized basis development novel therapeutics targeting use including cancer.