Inflammasome-targeting natural compounds in inflammatory bowel disease: Mechanisms and therapeutic potential

Xu, Qiuyun; Sun, Weichen; Zhang, Jie; Mei, Youmin; Bao, Jingyin; Hou, Shengping; Zhou, Xiaorong; Mao, Liming

doi:10.3389/fimmu.2022.963291

Cited by 14 publications

(12 citation statements)

References 130 publications

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“…Afterward, when the primed cell senses another stimulus, the activation and formation of NLRP3 inflammasome occur, following caspase-1 activation and the release of IL-1β and IL-18 [47]. It has been previously reported that NRLP3 may be associated with a variety of diseases, including inflammatory bowel diseases, atopic dermatitis, atherosclerosis, and diabetes mellitus type 2 [48][49][50]. The association of the NRLP3 pathway with HS was also reported.…”

Section: Nlrp3 Inflammasomementioning

confidence: 93%

Pathological and Therapeutical Implications of Pyroptosis in Psoriasis and Hidradenitis Suppurativa: A Narrative Review

Krajewski,

Tsoukas,

Szepietowski

2024

CIMB

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This manuscript explores the role of pyroptosis, an inflammatory programmed cell death, in the pathogenesis of two chronic dermatoses, psoriasis and hidradenitis suppurativa (HS). The diseases, though clinically diverse, share common pathogenetic pathways involving the unbalanced interaction between the adaptive and innate immune systems. This review focuses on the molecular changes in psoriatic and HS skin, emphasizing the activation of dendritic cells, secretion of interleukins (IL-17, IL-22, and TNF-α), and the involvement of inflammasomes, particularly NLRP3. This manuscript discusses the role of caspases, especially caspase-1, in driving pyroptosis and highlights the family of gasdermins (GSDMs) as key players in the formation of pores leading to cell rupture and the release of proinflammatory signals. This study delves into the potential therapeutic implications of targeting pyroptosis in psoriasis and HS, examining existing medications like biologics and Janus kinase inhibitors. It also reviews the current limitations and challenges in developing therapies that selectively target pyroptosis. Additionally, the manuscript explores the role of pyroptosis in various inflammatory disorders associated with psoriasis and HS, such as inflammatory bowel disease, diabetes mellitus, and cardiovascular disorders. The review concludes by emphasizing the need for further research to fully elucidate the pathomechanisms of these dermatoses and develop effective, targeted therapies.

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Section: Nlrp3 Inflammasomementioning

confidence: 93%

Pathological and Therapeutical Implications of Pyroptosis in Psoriasis and Hidradenitis Suppurativa: A Narrative Review

Krajewski,

Tsoukas,

Szepietowski

2024

CIMB

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“…NF-κB is activated when lymphocytes are activated and differentiated, as well as when innate cells produce pro-inflammatory cytokines. During the inflammasome activation process, NF-κB initiates the transcription of NLRP3 and Pro-IL-1β components ( Xu et al, 2022 ). The PLPs inhibit both NF-κB activation and proinflammatory molecule production such as pro-IL-1β, thus reducing the inflammatory response in mice colonic caused by DSS( Chen et al, 2021 ).…”

Section: Regulation Of Nlrp3 In Uc By Natural Productsmentioning

confidence: 99%

Natural products modulate NLRP3 in ulcerative colitis

Xue,

Yuan,

Hou

et al. 2023

Front. Pharmacol.

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Ulcerative colitis (UC) is a clinically common, progressive, devastating, chronic inflammatory disease of the intestine that is recurrent and difficult to treat. Nod-like receptor protein 3 (NLRP3) is a protein complex composed of multiple proteins whose formation activates cysteine aspartate protease-1 (caspase-1) to induce the maturation and secretion of inflammatory mediators such as interleukin (IL)-1β and IL-18, promoting the development of inflammatory responses. Recent studies have shown that NLRP3 is associated with UC susceptibility, and that it maintains a stable intestinal environment by responding to a wide range of pathogenic microorganisms. The mainstay of treatment for UC is to control inflammation and relieve symptoms. Despite a certain curative effect, there are problems such as easy recurrence after drug withdrawal and many side effects associated with long-term medication. NLRP3 serves as a core link in the inflammatory response. If the relationship between NLRP3 and gut microbes and inflammation-associated factors can be analyzed concerning its related inflammatory signaling pathways, its expression status as well as specific mechanism in the course of IBD can be elucidated and further considered for clinical diagnosis and treatment of IBD, it is expected that the development of lead compounds targeting the NLRP3 inflammasome can be developed for the treatment of IBD. Research into the prevention and treatment of UC, which has become a hotbed of research in recent years, has shown that natural products are rich in therapeutic means, and multi-targets, with fewer adverse effects. Natural products have shown promise in treating UC in numerous basic and clinical trials over the past few years. This paper describes the regulatory role of the NLRP3 inflammasome in UC and the mechanism of recent natural products targeting NLRP3 against UC, which provides a reference for the clinical treatment of this disease.

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“…NLRP6 has the ability to directly bind double-stranded (ds) RNA, which can recognize microbial metabolites ( 37 ). Liquid–liquid phase separation occurs when NLRP6 interacts with dsRNA ( 38 ). Moreover, lipoteihoic acid, a known NLRP6 ligand, can promote NLRP6 liquid–liquid phase separation, and the RNA helicase DHX15 can form a complex with NLRP6 and dsRNA ( 39 ).…”

Section: Composition and Classification Of Inflammasomesmentioning

confidence: 99%

Inflammasome and pyroptosis in autoimmune liver diseases

et al. 2023

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Autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), and IgG4-related sclerosing cholangitis (IgG4-SC) are the four main forms of autoimmune liver diseases (AILDs), which are all defined by an aberrant immune system attack on the liver. Most previous studies have shown that apoptosis and necrosis are the two major modes of hepatocyte death in AILDs. Recent studies have reported that inflammasome-mediated pyroptosis is critical for the inflammatory response and severity of liver injury in AILDs. This review summarizes our present understanding of inflammasome activation and function, as well as the connections among inflammasomes, pyroptosis, and AILDs, thus highlighting the shared features across the four disease models and gaps in our knowledge. In addition, we summarize the correlation among NLRP3 inflammasome activation in the liver-gut axis, liver injury, and intestinal barrier disruption in PBC and PSC. We summarize the differences in microbial and metabolic characteristics between PSC and IgG4-SC, and highlight the uniqueness of IgG4-SC. We explore the different roles of NLRP3 in acute and chronic cholestatic liver injury, as well as the complex and controversial crosstalk between various types of cell death in AILDs. We also discuss the most up-to-date developments in inflammasome- and pyroptosis-targeted medicines for autoimmune liver disorders.

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Inflammasome-targeting natural compounds in inflammatory bowel disease: Mechanisms and therapeutic potential

Cited by 14 publications

References 130 publications

Pathological and Therapeutical Implications of Pyroptosis in Psoriasis and Hidradenitis Suppurativa: A Narrative Review

Pathological and Therapeutical Implications of Pyroptosis in Psoriasis and Hidradenitis Suppurativa: A Narrative Review

Natural products modulate NLRP3 in ulcerative colitis

Inflammasome and pyroptosis in autoimmune liver diseases

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