Medicinal Plants, Phytochemicals and Regulation of the NLRP3 Inflammasome in Inflammatory Bowel Diseases: A Comprehensive Review

Abstract

Ongoing research explores the underlying causes of ulcerative colitis and Crohn's disease. Many experts suggest that dysbiosis in the gut microbiota and genetic, immunological, and environmental factors play significant roles. The term "microbiota" pertains to the collective community of microorganisms, including bacteria, viruses, and fungi, that reside within the gastrointestinal tract, with a particular emphasis on the colon. When there is an imbalance or disruption in the composition of the gut microbiota, it is referred to as dysbiosis. Dysbiosis can trigger inflammation in the intestinal cells and disrupt the innate immune system, leading to oxidative stress, redox signaling, electrophilic stress, and inflammation. The Nod-like Receptor (NLR) Family Pyrin Domain Containing 3 (NLRP3) inflammasome, a key regulator found in immunological and epithelial cells, is crucial in inducing inflammatory diseases, promoting immune responses to the gut microbiota, and regulating the integrity of the intestinal epithelium. Its downstream effectors include caspase-1 and interleukin (IL)-1β. The present study investigated the therapeutic potential of 13 medicinal plants, such as Litsea cubeba, Artemisia anomala, Piper nigrum, Morus macroura, and Agrimonia pilosa, and 29 phytocompounds such as artemisitene, morroniside, protopine, ferulic acid, quercetin, picroside II, and hydroxytyrosol on in vitro and in vivo models of inflammatory bowel diseases (IBD), with a focus on their effects on the NLRP3 inflammasome. The observed effects of these treatments included reductions in IL-1β, tumor necrosis factor-alpha, IL-6, interferon-gamma, and caspase levels, and increased expression of antioxidant enzymes, IL-4, and IL-10, as well as regulation of gut microbiota. These effects could potentially provide substantial advantages in treating IBD with few or no adverse effects as caused by synthetic anti-inflammatory and immunomodulated drugs. However, additional research is necessary to validate these findings clinically and to develop effective treatments that can benefit individuals who suffer from these diseases.

Keywords: Crohn’s disease; NLR Family Pyrin Domain Containing 3; NLRP3; cancer; inflammasome; inflammation; inflammatory bowel disease; medicinal plants; phytochemicals; ulcerative colitis.

Figure 1

The potential impact of phytochemicals in mitigating NLRP3 pathway activation in the context of IBD. ASC, Apoptosis-Associated Speck-Like Protein Containing a CARD; IFN-γ, interferon gama; IL, Interleukin; mRNA, messenger RNA; NF-kB, nuclear factor kappa b; NLR, Nod-like Receptor; NLRP3, NLR Family Pyrin Domain Containing 3; TLRs, Toll-like receptors; TFN-α, tumor factor necrosis alfa.

Figure 2

Flow diagram illustrating the literature search methodology of this review.

Figure 3

The main pathophysiological steps involved in the occurrence of UC and CD. ↑, increase; FOXP3, forkhead box P3; GATA3, GATA (Erythroid transcription factor) Binding Protein 3; IFN-γ, interferon gama; IL, interleukin; IRF4, Interferon regulatory factor 4; T-BET, T-box transcription factor TBX21; TGF-β, transforming growth factor beta; Th, T helper; TNF-α, tumor necrosis factor alfa; Treg, T regulatory cell.

Figure 4

NLRP3 inflammasome regulation with the use of curcumin. AIM2, Interferon-Inducible Protein AIM2; ATP, Adenosine Triphosphate; DAMPs, Damage-Associated Molecular Patterns; hsp70, Heat Shock Protein 70; hsp90, Heat Shock Protein 90; IL, Interleukin; NF-kB, Nuclear Factor Kappa b; NLR, Nod-like Receptor; NLRC5, NOD-like receptor family CARD domain containing 4; NLRC5, NOD-like receptor family CARD domain containing 5; NLRP1b, NLR family pyrin domain containing 1b; NLRP3, Nod-like Receptor Family Pyrin Domain Containing 3.