Curcumin and Intestinal Inflammatory Diseases: Molecular Mechanisms of Protection

Abstract

Intestinal inflammatory diseases, such as Crohn's disease, ulcerative colitis, and necrotizing enterocolitis, are becoming increasingly prevalent. While knowledge of the pathogenesis of these related diseases is currently incomplete, each of these conditions is thought to involve a dysfunctional, or overstated, host immunological response to both bacteria and dietary antigens, resulting in unchecked intestinal inflammation and, often, alterations in the intestinal microbiome. This inflammation can result in an impaired intestinal barrier allowing for bacterial translocation, potentially resulting in systemic inflammation and, in severe cases, sepsis. Chronic inflammation of this nature, in the case of inflammatory bowel disease, can even spur cancer growth in the longer-term. Recent research has indicated certain natural products with anti-inflammatory properties, such as curcumin, can help tame the inflammation involved in intestinal inflammatory diseases, thus improving intestinal barrier function, and potentially, clinical outcomes. In this review, we explore the potential therapeutic properties of curcumin on intestinal inflammatory diseases, including its antimicrobial and immunomodulatory properties, as well as its potential to alter the intestinal microbiome. Curcumin may play a significant role in intestinal inflammatory disease treatment in the future, particularly as an adjuvant therapy.

Keywords: Crohn’s disease; curcumin; inflammatory bowel disease; necrotizing enterocolitis; ulcerative colitis.

Figure 1

Schematic of TLR4/NF-κB/AP-1 signaling.

Figure 2

(Reprinted with permission from Dove Medical Press, Ltd.). Effect of FLLL32 and curcumin on IL-6-induced reduction of TEER in T84 monolayer. TEER value of T84 monolayers incubated with cell culture medium for 0–72 h in the presence of IL-6 (10 ng/mL) with FLLL32 (50 µM), curcumin (50 µM), or carrier (dimethyl sulfoxide) for 1 h in serum-free medium. ** p = 0.001 (IL-6 vs. IL-6 + FLLL32 at 24 h), **** p < 0.0001 (IL-6 vs. IL-6 + FLLL32 at 48 and 72 h), and # p = 0.003 (IL-6 vs. IL-6 + curcumin).

Figure 3

(Reprinted with permission from Dove Medical Press, Ltd.). FLLL32 attenuates intestinal inflammation and injury in DK NEC model. Representative H&E pictures from pups in the sham group (A), untreated NEC group (B), and NEC + FLLL32 group (C) (20× magnification). (D) Histological NEC scoring was obtained by two pathologists blinded to the groups (**** p < 0.0001). (E) FLLL32 preserved intestinal permeability in the NEC + FLLL32 group compared to the untreated group and control group (**** p < 0.0001). FLLL32 pretreatment reduced the levels of proinflammatory cytokines, TNF-α (F, p = 0.001), IL-6 (G, p < 0.001), IL-1β (H, p = 0.009), and GRO-α levels (I, p = 0.034) compared to pups in the untreated NEC group. Data are mean ± SEM. Results are representative of at least three separate experiments.