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.

Immunological dimensions of neuroinflammation and microglial activation: exploring innovative immunomodulatory approaches to mitigate neuroinflammatory progression

“…Inflammasomes are well-recognized pivotal components of the innate immune system. They typically include a ligand-sensing receptor, often belonging to the nucleotide-binding domain leucine-rich repeat (NLR) family (such as NLRP1, NLRP3, NLRC4, or AIM2), an adaptor protein (usually the apoptosis-associated speck-like protein containing a CARD domain [ASC]), and a pro-caspase (typically pro-caspase 1) ( 77 ). Upon receiving the appropriate stimulus, these receptors form oligomers and enlist pro-caspase 1 with the assistance of the ASC protein.…”

“…This upregulation is initiated by activating PRRs and cytokine receptors, including toll-like receptors (TLRs) and IL-1 receptors (IL-1R), in response to PAMPs and DAMPs, respectively. Subsequently, the activation phase of NLRP3 is prompted by either endogenous molecules, such as DAMPs, or external stimuli, like PAMPs, K+, and Cl− ions efflux, or the influx of Ca2+ ( 77 ).…”

“…Verily, the activation of the NLRP3 inflammasome is intricately connected to the development of a range of inflammatory and immunomodulated conditions such as diabetes, inflammatory bowel diseases, and atherosclerosis ( 77 ). Nevertheless, an excessive activation level is necessitated for NLRP3 to precipitate illness ( 116 ).…”

Antioxidant and Anti-Inflammatory Phytochemicals for the Treatment of Inflammatory Bowel Disease: A Systematic Review

“…Conversely, diet-derived antioxidants can modulate inflammation and gut microbiota [88]. Phytochemicals interact with the intestine by ameliorating oxidative stress, regulating cytokines, modulating gene expression and signaling to restore intestinal permeability [89,90]. By exerting antioxidative and antimicrobial actions, they may affect the structure of gut microbiota [91][92][93][94].…”

Inflammasomes Are Influenced by Epigenetic and Autophagy Mechanisms in Colorectal Cancer Signaling

“…In addition to promoting immune responses to the gut microbiota, the NLRP3 inflammasome regulates intestinal epithelial integrity. In a recent study, the therapeutic potential of 29 phytocompounds (e.g., artemisitene, morroniside, protopine, ferulic acid, quercetin, picroside II, and hydroxytyrosol) and 13 medicinal plants (e.g., Litsea cubeba , Artemisia anomala , Piper nigrum , Morus macroura , and Agrimonia pilosa ) was assessed for in vitro and in vivo models of IBD [ 128 ]. The study specifically examined the impact of these compounds on the NLRP3 inflammasome.…”