Phytochemicals and Regulation of NF-kB in Inflammatory Bowel Diseases: An Overview of In Vitro and In Vivo Effects

Abstract

Inflammatory bowel diseases (IBD) are chronic relapsing idiopathic inflammatory conditions affecting the gastrointestinal tract. They are mainly represented by two forms, ulcerative colitis (UC) and Crohn's disease (CD). IBD can be associated with the activation of nuclear factors, such as nuclear factor-kB (NF-kB), leading to increased transcription of pro-inflammatory mediators that result in diarrhea, abdominal pain, bleeding, and many extra-intestinal manifestations. Phytochemicals can interfere with many inflammation targets, including NF-kB pathways. Thus, this review aimed to investigate the effects of different phytochemicals in the NF-kB pathways in vitro and in vivo models of IBD. Fifty-six phytochemicals were included in this study, such as curcumin, resveratrol, kaempferol, sesamol, pinocembrin, astragalin, oxyberberine, berberine hydrochloride, botulin, taxifolin, naringin, thymol, isobavachalcone, lancemaside A, aesculin, tetrandrine, Ginsenoside Rk3, mangiferin, diosgenin, theanine, tryptanthrin, lycopene, gyngerol, alantolactone, mangostin, ophiopogonin D, fisetin, sinomenine, piperine, oxymatrine, euphol, artesunate, galangin, and nobiletin. The main observed effects related to NF-kB pathways were reductions in tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6, interferon-gamma (IFN-γ), and cyclooxygenase-2 (COX-2), and augmented occludin, claudin-1, zonula occludens-1, and IL-10 expression levels. Moreover, phytochemicals can improve weight loss, stool consistency, and rectal bleeding in IBD. Therefore, phytochemicals can constitute a powerful treatment option for IBD in humans.

Keywords: Crohn’s disease; NF-kB; anti-inflammatory; inflammation; inflammatory bowel diseases; intestinal inflammation; nuclear factor kappa B; phytochemicals; ulcerative colitis.

Figure 1

Inflammatory bowel diseases (IBD), activation of the nuclear factor-kB (NF-kB), and the possible roles of phytochemicals against this pathway activation during these diseases. ↑, increase; TLRs, Toll-like receptors; IKKα, IkappaB kinase alfa; IKKβ, IkappaB kinase beta; IKB, inhibitor of nuclear factor-kB.

Figure 2

NF-kB regulation with the use of curcumin. ↑, increase; ARE, antioxidant response elements; ASC, apoptosis-associated Speck-like protein; CAT, catalase; HO-1, heme oxygenase 1; GPX, glutathione; GST, glutathione S-transferases; IBD, inflammatory bowel diseases; Keap1, Kelch-like ECH-associated protein 1; MAPK, mitogen-activated protein kinases; NF-kB, nuclear factor-Kb; NLRP3, NLR (/nucleotide-binding leucine-rich repeat receptor) family pyrin domain containing 3; NQO1, NAD(P)H dehydrogenase (quinone) 1; Nrf2, nuclear factor erythroid 2–related factor 2; SOD1, superoxide dismutase 1; TAK1, transforming growth factor-β-activated kinase 1; TRAF6, tumor necrosis factor receptor (TNFR)-associated factor 6.

Figure 3

Main regulatory effects of RSV on NF-kB modulation during IBD. IL-6, interleukin 6; IL-10, interleukin 10; IL-12, interleukin 12; IL-17, interleukin 17; MHC, major histocompatibility complex; MPO, myeloperoxidase; NF-kB, nuclear factor-kB NF-kB; NO, nitric oxide; ROS, reactive oxygen species; TCR, T-cell receptor; Th0, T helper 0; Th1, T helper 1; Th2, T helper 2; Th17, T helper 17; TLR, Toll-like receptor; TNF-α, tumor factor necrosis alfa; Treg, regulatory T cell.