Progress in targeting the NLRP3 signaling pathway for inflammatory bowel disease (Review)

Gong,Yubo; Han,Zhenqi; Wang,Siyi; Li,Xuefeng; Chen,Xinhua; Yang,Bo

doi:10.3892/mmr.2025.13606

Progress in targeting the NLRP3 signaling pathway for inflammatory bowel disease (Review)

Authors:
- Yubo Gong
- Zhenqi Han
- Siyi Wang
- Xuefeng Li
- Xinhua Chen
- Bo Yang
View Affiliations

Affiliations: College of Acupuncture Massage, Changchun University of Traditional Chinese Medicine, Changchun, Jilin 130117, P.R. China, Endoscopy Department, The Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, Jilin 130021, P.R. China
Published online on: July 3, 2025 https://doi.org/10.3892/mmr.2025.13606
Article Number: 241
Copyright: © Gong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Inflammatory caspases pro‑inflammatory cytokines, such as IL‑1β IL‑18, constitute a critical part in the modulation of innate immune responses by the nucleotide‑binding domain leucine‑rich repeat protein (NLRP)3 inflammasome. The NLRP3 inflammasome, a cytosolic complex, is composed of three distinct classes of proteins‑sensor complexes, adaptor proteins, cysteine proteases. It is well‑established that this pathway can powerfully influence the pathophysiology of autoimmune diseases along with an association of a plethora of inflammatory conditions. Therefore, it is of great significance to elucidate the mechanisms through which NLRP3 participates in disease development functions as a potential target for pharmacological intervention. The present review discussed the function role of the NLRP3 inflammasome in inflammatory bowel disease and described the structure assembly and activation mechanism of the NLRP3 inflammasome. Additionally, it explored novel clinical viewpoints and therapeutic advances in targeted NLRP3 inflammasome therapy. In conclusion, the present review offered a comprehensive overview of inflammatory bowel disease and the NLRP3 inflammasome. It is expected to serve as a guide for future research, potentially leading to improved patient outcomes. The present review has been submitted as a pre‑print (https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4962722).

View Figures

View References

1	Park J, Jeong GH, Song M, Yon DK, Lee SW, Koyanagi A, Jacob L, Kostev K, Dragioti E, Radua J, et al: The global, regional, and national burden of inflammatory bowel diseases, 1990–2019: A systematic analysis for the global burden of disease study 2019. Dig Liver Dis. 55:1352–1359. 2023. View Article : Google Scholar : PubMed/NCBI
2	Franzosa EA, Sirota-Madi A, Avila-Pacheco J, Fornelos N, Haiser HJ, Reinker S, Vatanen T, Hall AB, Mallick H, McIver LJ, et al: Gut microbiome structure and metabolic activity in inflammatory bowel disease. Nat Microbiol. 4:293–305. 2019. View Article : Google Scholar
3	Jeong DY, Kim S, Son MJ, Son CY, Kim JY, Kronbichler A, Lee KH and Shin JI: Induction and maintenance treatment of inflammatory bowel disease: A comprehensive review. Autoimmun Rev. 18:439–454. 2019. View Article : Google Scholar : PubMed/NCBI
4	Na SY and Moon W: Perspectives on current and novel treatments for inflammatory bowel disease. Gut Liver. 13:604–616. 2019. View Article : Google Scholar : PubMed/NCBI
5	Duan Y, Kelley N and He Y: Role of the NLRP3 inflammasome in neurodegenerative diseases and therapeutic implications. Neural Regen Res. 15:1249–1250. 2020. View Article : Google Scholar : PubMed/NCBI
6	Broz P and Dixit VM: Inflammasomes: Mechanism of assembly, regulation and signalling. Nat Rev Immunol. 16:407–420. 2016. View Article : Google Scholar
7	Paik S, Kim JK, Silwal P, Sasakawa C and Jo EK: An update on the regulatory mechanisms of NLRP3 inflammasome activation. Cell Mol Immunol. 18:1141–1160. 2021. View Article : Google Scholar
8	Kodi T, Sankhe R, Gopinathan A, Nandakumar K and Kishore A: New Insights on NLRP3 Inflammasome: Mechanisms of activation, inhibition, and epigenetic regulation. J Neuroimmune Pharmacol. 19:72024. View Article : Google Scholar
9	Abo-Ouf H, Hooper AW, White EJ, Janse van Rensburg HJ, Trigatti BL and Igdoura SA: Deletion of tumor necrosis factor-α ameliorates neurodegeneration in Sandhoff disease mice. Hum Mol Genet. 22:3960–3975. 2013. View Article : Google Scholar
10	Xu Z, Kombe Kombe AJ, Deng S, Zhang H, Wu S, Ruan J, Zhou Y and Jin T: NLRP inflammasomes in health and disease. Mol Biomed. 5:142024. View Article : Google Scholar : PubMed/NCBI
11	Hong H, Kim BS and Im HI: Pathophysiological role of neuroinflammation in neurodegenerative diseases and psychiatric disorders. Int Neurourol J. 20 (Suppl 1):S2–S7. 2016. View Article : Google Scholar : PubMed/NCBI
12	Herman FJ and Pasinetti GM: Principles of inflammasome priming and inhibition: Implications for psychiatric disorders. Brain Behav Immun. 73:66–84. 2018. View Article : Google Scholar : PubMed/NCBI
13	Xiang H, Zhu F, Xu Z and Xiong J: Role of inflammasomes in kidney diseases via both canonical and Non-canonical pathways. Front Cell Dev Biol. 8:1062020. View Article : Google Scholar
14	Bauernfeind FG, Horvath G, Stutz A, Alnemri ES, MacDonald K, Speert D, Fernandes-Alnemri T, Wu J, Monks BG, Fitzgerald KA, et al: Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. J Immunol. 183:787–791. 2009. View Article : Google Scholar
15	Franchi L, Eigenbrod T and Núñez G: Cutting edge: TNF-alpha mediates sensitization to ATP and silica via the NLRP3 inflammasome in the absence of microbial stimulation. J Immunol. 183:792–796. 2009. View Article : Google Scholar
16	Xing Y, Yao X, Li H, Xue G, Guo Q, Yang G, An L, Zhang Y and Meng G: Cutting Edge: TRAF6 mediates TLR/IL-1R signaling-induced nontranscriptional priming of the NLRP3 inflammasome. J Immunol. 199:1561–1566. 2017. View Article : Google Scholar
17	Mangan MSJ, Olhava EJ, Roush WR, Seidel HM, Glick GD and Latz E: Targeting the NLRP3 inflammasome in inflammatory diseases. Nat Rev Drug Discov. 17:588–606. 2018. View Article : Google Scholar : PubMed/NCBI
18	Franchi L, Eigenbrod T, Muñoz-Planillo R and Nuñez G: The inflammasome: A caspase-1-activation platform that regulates immune responses and disease pathogenesis. Nat Immunol. 10:241–247. 2009. View Article : Google Scholar
19	Swanson KV, Deng M and Ting JP: The NLRP3 inflammasome: Molecular activation and regulation to therapeutics. Nat Rev Immunol. 19:477–489. 2019. View Article : Google Scholar
20	Shimada K, Crother TR, Karlin J, Dagvadorj J, Chiba N, Chen S, Ramanujan VK, Wolf AJ, Vergnes L, Ojcius DM, et al: Oxidized mitochondrial DNA activates the NLRP3 inflammasome during apoptosis. Immunity. 36:401–414. 2012. View Article : Google Scholar : PubMed/NCBI
21	Liu J, Jia Z and Gong W: Circulating mitochondrial DNA stimulates innate immune signaling pathways to mediate acute kidney injury. Front Immunol. 12:6806482021. View Article : Google Scholar
22	Pellegrini C, Fornai M, Antonioli L, Blandizzi C and Calderone V: Phytochemicals as novel therapeutic strategies for NLRP3 inflammasome-related neurological, metabolic, and inflammatory diseases. Int J Mol Sci. 20:28762019. View Article : Google Scholar
23	Muñoz-Planillo R, Kuffa P, Martínez-Colón G, Smith BL, Rajendiran TM and Núñez G: K+ efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter. Immunity. 38:1142–1153. 2013. View Article : Google Scholar
24	Rossol M, Pierer M, Raulien N, Quandt D, Meusch U, Rothe K, Schubert K, Schöneberg T, Schaefer M, Krügel U, et al: Extracellular Ca2+ is a danger signal activating the NLRP3 inflammasome through G protein-coupled calcium sensing receptors. Nat Commun. 3:13292012. View Article : Google Scholar : PubMed/NCBI
25	Lee GS, Subramanian N, Kim AI, Aksentijevich I, Goldbach-Mansky R, Sacks DB, Germain RN, Kastner DL and Chae JJ: The calcium-sensing receptor regulates the NLRP3 inflammasome through Ca2+ and cAMP. Nature. 492:123–127. 2012. View Article : Google Scholar : PubMed/NCBI
26	Werner LE and Wagner U: Calcium-sensing receptor-mediated NLRP3 inflammasome activation in rheumatoid arthritis and autoinflammation. Front Physiol. 13:10785692023. View Article : Google Scholar
27	Tang T, Lang X, Xu C, Wang X, Gong T, Yang Y, Cui J, Bai L, Wang J, Jiang W and Zhou R: CLICs-dependent chloride efflux is an essential and proximal upstream event for NLRP3 inflammasome activation. Nat Commun. 8:2022017. View Article : Google Scholar : PubMed/NCBI
28	Hornung V, Bauernfeind F, Halle A, Samstad EO, Kono H, Rock KL, Fitzgerald KA and Latz E: Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat Immunol. 9:847–856. 2008. View Article : Google Scholar
29	Cassel SL, Eisenbarth SC, Iyer SS, Sadler JJ, Colegio OR, Tephly LA, Carter AB, Rothman PB, Flavell RA and Sutterwala FS: The Nalp3 inflammasome is essential for the development of silicosis. Proc Natl Acad Sci USA. 105:9035–9040. 2008. View Article : Google Scholar : PubMed/NCBI
30	Halle A, Hornung V, Petzold GC, Stewart CR, Monks BG, Reinheckel T, Fitzgerald KA, Latz E, Moore KJ and Golenbock DT: The NALP3 inflammasome is involved in the innate immune response to amyloid-beta. Nat Immunol. 9:857–865. 2008. View Article : Google Scholar
31	Kelley N, Jeltema D, Duan Y and He YY: The NLRP3 inflammasome: An overview of mechanisms of activation and regulation. Int J Mol Sci. 20:33282019. View Article : Google Scholar
32	Netea MG, Nold-Petry CA, Nold MF, Joosten LA, Opitz B, van der Meer JH, van de Veerdonk FL, Ferwerda G, Heinhuis B, Devesa I, et al: Differential requirement for the activation of the inflammasome for processing and release of IL-1beta in monocytes and macrophages. Blood. 113:2324–2335. 2009. View Article : Google Scholar : PubMed/NCBI
33	Wang ZK, Yang YS, Chen Y, Yuan J, Sun G and Peng LH: Intestinal microbiota pathogenesis and fecal microbiota transplantation for inflammatory bowel disease. World J Gastroenterol. 20:14805–14820. 2014. View Article : Google Scholar
34	Yang F, He Z, Pan X, Xie S, Liang X, Geng L, Xu W and Gong S: Enhancing intestinal epithelial microtubule stability could alleviate IBD symptoms. Cell Commun Signal. 23:2632025. View Article : Google Scholar
35	Hugot JP, Laurent-Puig P, Gower-Rousseau C, Olson JM, Lee JC, Beaugerie L, Naom I, Dupas JL, Van Gossum A, Orholm M, et al: Mapping of a susceptibility locus for Crohn's disease on chromosome 16. Nature. 379:821–823. 1996. View Article : Google Scholar : PubMed/NCBI
36	Ogura Y, Bonen DK, Inohara N, Nicolae DL, Chen FF, Ramos R, Britton H, Moran T, Karaliuskas R, Duerr RH, et al: A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature. 411:603–606. 2001. View Article : Google Scholar : PubMed/NCBI
37	Nayar S, Morrison JK, Giri M, Gettler K, Chuang LS, Walker LA, Ko HM, Kenigsberg E, Kugathasan S, Merad M, et al: A myeloid-stromal niche and gp130 rescue in NOD2-driven Crohn's disease. Nature. 593:275–281. 2021. View Article : Google Scholar : PubMed/NCBI
38	Liu JZ, van Sommeren S, Huang H, Ng SC, Alberts R, Takahashi A, Ripke S, Lee JC, Jostins L, Shah T, et al: Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations. Nat Genet. 47:979–986. 2015. View Article : Google Scholar
39	Chen GB, Lee SH, Brion MJ, Montgomery GW, Wray NR, Radford-Smith GL and Visscher PM; International IBD Genetics Consortium, : Estimation and partitioning of (co)heritability of inflammatory bowel disease from GWAS and immunochip data. Hum Mol Genet. 23:4710–4720. 2014. View Article : Google Scholar
40	Cao G, Luo Q, Wu Y and Chen G: Inflammatory bowel disease and rheumatoid arthritis share a common genetic structure. Front Immunol. 15:13598572024. View Article : Google Scholar
41	Wang X, Li T and Chen Q: Causal relationship between ulcerative colitis and male infertility: A two-sample Mendelian randomization study. PLoS One. 19:e03038272024. View Article : Google Scholar : PubMed/NCBI
42	Jia K and Shen J: Transcriptome-wide association studies associated with Crohn's disease: Challenges and perspectives. Cell Biosci. 14:292024. View Article : Google Scholar
43	Juillerat P, Pittet V, Bulliard JL, Guessous I, Antonino AT, Mottet C, Felley C, Vader JP and Michetti P: Prevalence of inflammatory bowel disease in the canton of vaud (Switzerland): A population-based cohort study. J Crohns Colitis. 2:131–141. 2008. View Article : Google Scholar : PubMed/NCBI
44	Ng SC, Bernstein CN, Vatn MH, Lakatos PL, Loftus EV Jr, Tysk C, O'Morain C, Moum B and Colombel JF; Epidemiology Natural History Task Force of the International Organization of Inflammatory Bowel Disease (IOIBD), : Geographical variability and environmental risk factors in inflammatory bowel disease. Gut. 62:630–649. 2013. View Article : Google Scholar
45	Braegger CP, Ballabeni P, Rogler D, Vavricka SR, Friedt M and Pittet V; Swiss IBD Cohort Study Group, : Epidemiology of inflammatory bowel disease: Is there a shift toward onset at a younger age? J Pediatr Gastroenterol Nutr. 53:141–144. 2011. View Article : Google Scholar : PubMed/NCBI
46	Molodecky NA, Soon IS, Rabi DM, Ghali WA, Ferris M, Chernoff G, Benchimol EI, Panaccione R, Ghosh S, Barkema HW and Kaplan GG: Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology. 142:e46–e30. 2012. View Article : Google Scholar
47	Wild CP: Complementing the genome with an ‘exposome’: The outstanding challenge of environmental exposure measurement in molecular epidemiology. Cancer Epidemiol Biomarkers Prev. 14:1847–1850. 2005. View Article : Google Scholar : PubMed/NCBI
48	Rogler G and Vavricka SL: Exposome in IBD: Recent insights in environmental factors that influence the onset and course of IBD. Inflamm Bowel Dis. 21:400–408. 2015. View Article : Google Scholar : PubMed/NCBI
49	Ananthakrishnan AN, McGinley EL, Binion DG and Saeian K: Ambient air pollution correlates with hospitalizations for inflammatory bowel disease: An ecologic analysis. Inflamm Bowel Dis. 17:1138–1145. 2011. View Article : Google Scholar : PubMed/NCBI
50	Andersen V, Olsen A, Carbonnel F, Tjønneland A and Vogel U: Diet and risk of inflammatory bowel disease. Dig Liver Dis. 44:185–194. 2012. View Article : Google Scholar : PubMed/NCBI
51	Sandu O, Song K, Cai W, Zheng F, Uribarri J and Vlassara H: Insulin resistance and type 2 diabetes in high-fat-fed mice are linked to high glycotoxin intake. Diabetes. 54:2314–2319. 2005. View Article : Google Scholar : PubMed/NCBI
52	Martini GA and Brandes JW: Increased consumption of refined carbohydrates in patients with Crohn's disease. Klin Wochenschr. 54:367–371. 1976. View Article : Google Scholar : PubMed/NCBI
53	D'Souza S, Levy E, Mack D, Israel D, Lambrette P, Ghadirian P, Deslandres C, Morgan K, Seidman EG and Amre DK: Dietary patterns and risk for Crohn's disease in children. Inflamm Bowel Dis. 14:367–373. 2008. View Article : Google Scholar
54	Danese S, Sans M and Fiocchi C: Inflammatory bowel disease: The role of environmental factors. Autoimmun Rev. 3:394–400. 2004. View Article : Google Scholar : PubMed/NCBI
55	Alperen CC, Soydas B, Serin E, Erbayrak M, Savas NA, Unler GK, Meral CE, Toprak U, Boyacioglu AS and Dagli U: Role of environmental risk factors in the etiology of inflammatory bowel diseases: A Multicenter Study. Dig Dis Sci. 69:2927–2936. 2024. View Article : Google Scholar
56	Kronman MP, Zaoutis TE, Haynes K, Feng R and Coffin SE: Antibiotic exposure and IBD development among children: A population-based cohort study. Pediatrics. 130:e794–e803. 2012. View Article : Google Scholar : PubMed/NCBI
57	Narula N, Wong ECL, Pray C, Marshall JK, Rangarajan S, Islam S, Bahonar A, Alhabib KF, Kontsevaya A, Ariffin F, et al: Associations of antibiotics, hormonal therapies, oral contraceptives, and Long-term NSAIDS with inflammatory bowel disease: Results from the prospective urban rural epidemiology (PURE) Study. Clin Gastroenterol Hepatol. 21:2649–2659.e16. 2023. View Article : Google Scholar
58	Cornish JA, Tan E, Simillis C, Clark SK, Teare J and Tekkis PP: The risk of oral contraceptives in the etiology of inflammatory bowel disease: A meta-analysis. Am J Gastroenterol. 103:2394–2400. 2008. View Article : Google Scholar
59	Cosnes J, Carbonnel F, Beaugerie L, Le Quintrec Y and Gendre JP: Effects of cigarette smoking on the long-term course of Crohn's disease. Gastroenterology. 110:424–431. 1996. View Article : Google Scholar : PubMed/NCBI
60	Thomas GA, Rhodes J and Green JT: Inflammatory bowel disease and smoking-a review. Am J Gastroenterol. 93:144–149. 1998. View Article : Google Scholar
61	Birrenbach T and Böcker U: Inflammatory bowel disease and smoking: A review of epidemiology, pathophysiology, and therapeutic implications. Inflamm Bowel Dis. 10:848–859. 2004. View Article : Google Scholar : PubMed/NCBI
62	Mentella MC, Scaldaferri F, Pizzoferrato M, Gasbarrini A and Miggiano GAD: Nutrition, IBD and Gut Microbiota: A review. Nutrients. 12:9442020. View Article : Google Scholar : PubMed/NCBI
63	de Mattos BR, Garcia MP, Nogueira JB, Paiatto LN, Albuquerque CG, Souza CL, Fernandes LG, Tamashiro WM and Simioni PU: Inflammatory bowel disease: An overview of immune mechanisms and biological treatments. Mediators Inflamm. 2015:4930122015. View Article : Google Scholar : PubMed/NCBI
64	Chen Y, Cui W, Li X and Yang H: Interaction between commensal bacteria, immune response and the intestinal barrier in inflammatory bowel disease. Front Immunol. 12:7619812021. View Article : Google Scholar
65	Flint HJ, Scott KP, Louis P and Duncan SH: The role of the gut microbiota in nutrition and health. Nat Rev Gastroenterol Hepatol. 9:577–589. 2012. View Article : Google Scholar
66	Shreiner AB, Kao JY and Young VB: The gut microbiome in health and in disease. Curr Opin Gastroenterol. 31:69–75. 2015. View Article : Google Scholar
67	Li T and Chiang JYL: Bile acid signaling in metabolic and inflammatory diseases and drug development. Pharmacol Rev. 76:1221–1253. 2024. View Article : Google Scholar : PubMed/NCBI
68	Li S, Chen J, Zheng Y and Zhang Y: Weissella paramesenteroides NRIC1542 inhibits dextran sodium sulfate-induced colitis in mice through regulating gut microbiota and SIRT1/NF-κB signaling pathway. FASEB J. 38:e237912024. View Article : Google Scholar : PubMed/NCBI
69	Taurog JD, Richardson JA, Croft JT, Simmons WA, Zhou M, Fernández-Sueiro JL, Balish E and Hammer RE: The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats. J Exp Med. 180:2359–2364. 1994. View Article : Google Scholar : PubMed/NCBI
70	Veltkamp C, Tonkonogy SL, De Jong YP, Albright C, Grenther WB, Balish E, Terhorst C and Sartor RB: Continuous stimulation by normal luminal bacteria is essential for the development and perpetuation of colitis in Tg(epsilon26) mice. Gastroenterology. 120:900–913. 2001. View Article : Google Scholar : PubMed/NCBI
71	Singh V, Yeoh BS, Walker RE, Xiao X, Saha P, Golonka RM, Cai J, Bretin ACA, Cheng X, Liu Q, et al: Microbiota fermentation-NLRP3 axis shapes the impact of dietary fibers on intestinal inflammation. Gut. 68:1801–1812. 2019. View Article : Google Scholar
72	Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A and Bray F: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 71:209–249. 2021. View Article : Google Scholar : PubMed/NCBI
73	Ardizzone A, Capra AP, Repici A, Lanza M, Bova V, Palermo N, Paterniti I and Esposito E: Rebalancing NOX2/Nrf2 to limit inflammation and oxidative stress across gut-brain axis in migraine. Free Radic Biol Med. 213:65–78. 2024. View Article : Google Scholar : PubMed/NCBI
74	Zhou L, Liu T, Huang B, Luo M, Chen Z, Zhao Z, Wang J, Leung D, Yang X, Chan KW, et al: Excessive deubiquitination of NLRP3-R779C variant contributes to very-early-onset inflammatory bowel disease development. J Allergy Clin Immunol. 147:267–279. 2021. View Article : Google Scholar
75	Guan Y, Cheng H, Zhang N, Cai Y, Zhang Q, Jiang X, Wang A, Zeng H and Jia B: The role of the esophageal and intestinal microbiome in gastroesophageal reflux disease: Past, present, and future. Front Immunol. 16:15584142025. View Article : Google Scholar
76	Yuan S, Liu BH, Cheng WW, Meng H, Hou XT, Xue JC, Zhang HM and Zhang QG: Polyphyllin VI modulates macrophage polarization through autophagy-NLRP3 inflammasome to alleviate inflammatory bowel disease. Phytomedicine. 143:1566402025. View Article : Google Scholar : PubMed/NCBI
77	Keane S, Herring M, Rolny P, Wettergren Y and Ejeskär K: Inflammation suppresses DLG2 expression decreasing inflammasome formation. J Cancer Res Clin Oncol. 148:2295–2311. 2022. View Article : Google Scholar
78	Lin X, Xu M, Lan R, Hu D, Zhang S, Zhang S, Lu Y, Sun H, Yang J, Liu L and Xu J: Gut commensal Alistipes shahii improves experimental colitis in mice with reduced intestinal epithelial damage and cytokine secretion. mSystems. 10:e0160724205 View Article : Google Scholar
79	Li H, Fan C, Lu H, Feng C, He P, Yang X, Xiang C, Zuo J and Tang W: Protective role of berberine on ulcerative colitis through modulating enteric glial cells-intestinal epithelial cells-immune cells interactions. Acta Pharm Sin B. 10:447–461. 2020. View Article : Google Scholar : PubMed/NCBI
80	Lee SH, Hu LL, Gonzalez-Navajas J, Seo GS, Shen C, Brick J, Herdman S, Varki N, Corr M, Lee J and Raz E: ERK activation drives intestinal tumorigenesis in Apc min/+ mice. Nat Med. 16:665–670. 2010. View Article : Google Scholar : PubMed/NCBI
81	Wang SL, Zhang MM, Zhou H, Su GQ, Ding Y, Xu GH, Wang X, Li CF, Huang WF and Yi LT: Inhibition of NLRP3 attenuates sodium dextran sulfate-induced inflammatory bowel disease through gut microbiota regulation. Biomed J. 46:1005802023. View Article : Google Scholar : PubMed/NCBI
82	Tan G, Huang C, Chen J, Chen B and Zhi F: Gasdermin-E-mediated pyroptosis participates in the pathogenesis of Crohn's disease by promoting intestinal inflammation. Cell Rep. 35:1092652021. View Article : Google Scholar : PubMed/NCBI
83	Chen B, Dong X, Zhang JL, Sun X, Zhou L, Zhao K, Deng H and Sun Z: Natural compounds target programmed cell death (PCD) signaling mechanism to treat ulcerative colitis: A review. Front Pharmacol. 15:13336572024. View Article : Google Scholar
84	Wang M, Xu B, Liu L and Wang D: Oridonin attenuates dextran sulfate sodium-induced ulcerative colitis in mice via the Sirt1/NF-κB/p53 pathway. Mol Med Rep. 26:3122022. View Article : Google Scholar : PubMed/NCBI
85	Xu Q, Sun W, Zhang J, Mei Y, Bao J, Hou S, Zhou X and Mao L: Inflammasome-targeting natural compounds in inflammatory bowel disease: Mechanisms and therapeutic potential. Front Immunol. 13:9632912022. View Article : Google Scholar
86	Zhou ZJ, Dong JY, Qiu Y, Zhang GL, Wei K, He LH, Sun YN, Jiang HZ, Zhang SS, Guo XR, et al: Sulforaphane decreases oxidative stress and inhibits NLRP3 inflammasome activation in a mouse model of ulcerative colitis. Biomed Pharmacother. 175:1167062024. View Article : Google Scholar : PubMed/NCBI
87	Salem MB, El-Lakkany NM, Hammam OA and Seif El-Din SH: Bacillus clausii spores maintain gut homeostasis in murine ulcerative colitis via modulating microbiota, apoptosis, and the TXNIP/NLRP3 inflammasome cascade. Toxicol Rep. 14:1018582024. View Article : Google Scholar : PubMed/NCBI
88	Dharmapuri G, Kotha AK, Kalangi SK and Reddanna P: Mangiferin, a naturally occurring glucosylxanthone, induces apoptosis in Caco-2 cells in vitro and exerts protective effects on acetic Acid-induced ulcerative colitis in mice through the regulation of NLRP3. ACS Pharmacol Transl Sci. 7:1270–1277. 2024. View Article : Google Scholar
89	Chen Y, Niu Y, Hao W, Zhang W, Lu J, Zhou J, Du L and Xie W: Pineapple leaf phenols attenuate DSS-induced colitis in mice and inhibit inflammatory damage by targeting the NF-κB pathway. Molecules. 26:76562021. View Article : Google Scholar : PubMed/NCBI
90	Marinho S, Illanes M, Ávila-Román J, Motilva V and Talero E: Anti-inflammatory effects of rosmarinic Acid-loaded nanovesicles in acute colitis through modulation of NLRP3 inflammasome. Biomolecules. 11:1622021. View Article : Google Scholar : PubMed/NCBI
91	Zhang HX, Li YY, Liu ZJ and Wang JF: Quercetin effectively improves LPS-induced intestinal inflammation, pyroptosis, and disruption of the barrier function through the TLR4/NF-κB/NLRP3 signaling pathway in vivo and in vitro. Food Nutr Res. Dec 30–2022.(Epub ahead of print). doi: 10.29219/fnr.v66.8948. View Article : Google Scholar
92	Tian HM, Wang SP, Wang HY and Lu XM: Protective effect of naringin on NLRP3 inflammasome in newborn mice with necrotizing enterocolitis. Chin J Immunol. 1196–1200. 2021.
93	Qu Y, Li X, Xu F, Zhao S, Wu X, Wang Y and Xie J: Kaempferol alleviates murine experimental colitis by restoring gut microbiota and inhibiting the LPS-TLR4-NF-κB axis. Front Immunol. 12:6798972021. View Article : Google Scholar
94	Liu Q, Zuo R, Wang K, Nong FF, Fu YJ, Huang SW, Pan ZF, Zhang Y, Luo X, Deng XL, et al: Oroxindin inhibits macrophage NLRP3 inflammasome activation in DSS-induced ulcerative colitis in mice via suppressing TXNIP-dependent NF-κB pathway. Acta Pharmacol Sin. 41:771–781. 2020. View Article : Google Scholar : PubMed/NCBI
95	Sergent T, Piront N, Meurice J, Toussaint O and Schneider YJ: Anti-inflammatory effects of dietary phenolic compounds in an in vitro model of inflamed human intestinal epithelium. Chem Biol Interact. 188:659–667. 2010. View Article : Google Scholar
96	Kim DH, Hossain MA, Kang YJ, Jang JY, Lee YJ, Im E, Yoon JH, Kim HS, Chung HY and Kim ND: Baicalein, an active component of Scutellaria baicalensis Georgi, induces apoptosis in human colon cancer cells and prevents AOM/DSS-induced colon cancer in mice. Int J Oncol. 43:1652–1658. 2013. View Article : Google Scholar
97	Dong J, Liang W, Wang T, Sui J, Wang J, Deng Z and Chen D: Saponins regulate intestinal inflammation in colon cancer and IBD. Pharmacol Re. 144:66–72. 2019. View Article : Google Scholar
98	Rhule A, Navarro S, Smith JR and Shepherd DM: Panax notoginseng attenuates LPS-induced pro-inflammatory mediators in RAW264.7 cells. J Ethnopharmacol. 106:121–128. 2006. View Article : Google Scholar
99	Joh EH, Lee IA, Jung IH and Kim DH: Ginsenoside Rb1 and its metabolite compound K inhibit IRAK-1 activation-the key step of inflammation. Biochem Pharmacol. 82:278–286. 2011. View Article : Google Scholar
100	Wu CF, Bi XL, Yang JY, Zhan JY, Dong YX, Wang JH, Wang JM, Zhang R and Li X: Differential effects of ginsenosides on NO and TNF-alpha production by LPS-activated N9 microglia. Int Immunopharmacol. 7:313–320. 2007. View Article : Google Scholar
101	Lee IA, Hyam SR, Jang SE, Han MJ and Kim DH: Ginsenoside Re ameliorates inflammation by inhibiting the binding of lipopolysaccharide to TLR4 on macrophages. J Agric Food Chem. 60:9595–9602. 2012. View Article : Google Scholar : PubMed/NCBI
102	Xue JC, Yuan S, Hou XT, Meng H, Liu BH, Cheng WW, Zhao M, Li HB, Guo XF, Di C, et al: Natural products modulate NLRP3 in ulcerative colitis. Front Pharmacol. 14:12658252023. View Article : Google Scholar
103	Lee SM: Anti-inflammatory effects of ginsenosides Rg5, Rz1, and Rk1: Inhibition of TNF-α-induced NF-κB, COX-2, and iNOS transcriptional expression. Phytother Res. 28:1893–1896. 2014. View Article : Google Scholar : PubMed/NCBI
104	Liu C, Wang J, Yang Y, Liu X, Zhu Y, Zou J, Peng S, Le TH, Chen Y, Zhao S, et al: Ginsenoside Rd ameliorates colitis by inducing p62-driven mitophagy-mediated NLRP3 inflammasome inactivation in mice. Biochem Pharmacol. 155:366–379. 2018. View Article : Google Scholar
105	Christianson DW: Structural and chemical biology of terpenoid cyclases. Chem Rev. 117:11570–11648. 2017. View Article : Google Scholar : PubMed/NCBI
106	Tian Z, Liu Y, Yang B, Zhang J, He H, Ge H, Wu Y and Shen Z: Astagalus polysaccharide attenuates murine colitis through inhibiton of the NLRP3 inflammasome. Planta Med. 83:70–77. 2017. View Article : Google Scholar : PubMed/NCBI
107	Dai J, Wang W, He F, Wang Y and Zou D: Alleviation of DSS-induced colitis by Meconopsis polysaccharides correlated with reduced PI3K/AKT signaling and gut microbiome diversity. Front Pharmacol. 16:14596682025. View Article : Google Scholar
108	Zhou YX, Gong XH, Zhang H and Peng C: A review on the pharmacokinetics of paeoniflorin and its anti-inflammatory and immunomodulatory effects. Biomed Pharmacother. 130:1105052020. View Article : Google Scholar : PubMed/NCBI
109	Fan Q, Guan X, Hou Y, Liu Y, Wei W, Cai X, Zhang Y, Wang G, Zheng X and Hao H: Paeoniflorin modulates gut microbial production of indole-3-lactate and epithelial autophagy to alleviate colitis in mice. Phytomedicine. 79:1533452020. View Article : Google Scholar : PubMed/NCBI
110	Selvakumar D, Evans D, Coyte KZ, McLaughlin J, Brass A, Hancock L and Cruickshank S: Understanding the development and function of the gut microbiota in health and inflammation. Frontline Gastroenterol. 13:e13–e21. 2022. View Article : Google Scholar
111	Dupont HL, Jiang ZD, Dupont AW and Utay NS: The intestinal microbiome in human health and disease. Trans Am Clin Climatol Assoc. 131:178–197. 2020.
112	Martel J, Chang SH, Ko YF, Hwang TL, Young JD and Ojcius DM: Gut barrier disruption and chronic disease. Trends Endocrinol Metabolism. 33:247–265. 2022. View Article : Google Scholar
113	Luo Y, Huang X, Hu H, Wang Y, Feng X, Chen S and Luo H: Intestinal microflora promotes Th2-mediated immunity through NLRP3 in damp and heat environments. Front Immunol. 15:13670532024. View Article : Google Scholar
114	Yuan Z, Yang L, Zhang X, Ji P, Hua Y and Wei Y: Huang-lian-jie-du decoction ameliorates acute ulcerative colitis in mice by regulating NF-κB and Nrf2 signaling pathways and enhancing intestinal barrier function. Front Pharmacol. 10:4729662019. View Article : Google Scholar
115	Tang X, Zeng T, Deng W, Zhao W, Liu Y, Huang Q, Deng Y, Xie W and Huang W: Gut microbe-derived betulinic acid alleviates sepsis-induced acute liver injury by inhibiting macrophage NLRP3 inflammasome in mice. mBio. 16:e03020242025. View Article : Google Scholar : PubMed/NCBI
116	Li X, Lin D, Hu X, Shi X, Huang W, Ouyang Y, Chen X, Xiong Y, Wu X, Hong D and Chen H: Akkermansia muciniphila modulates central nervous system autoimmune response and cognitive impairment by inhibiting hippocampal NLRP3-mediated Neuroinflammation. CNS Neurosci Ther. 31:e703202025. View Article : Google Scholar : PubMed/NCBI
117	Shen XH, Guan J, Lu DP, Hong SC, Yu L and Chen X: Peptostreptococcus anaerobius enhances dextran sulfate sodium-induced colitis by promoting nf-κB-NLRP3-dependent macrophage pyroptosis. Virulence. 15:24353912024. View Article : Google Scholar : PubMed/NCBI
118	Wei X, Leng X, Li G, Wang R, Chi L and Sun D: Advances in research on the effectiveness and mechanism of Traditional Chinese Medicine formulas for colitis-associated colorectal cancer. Front Pharmacol. 14:11206722023. View Article : Google Scholar
119	Chen Y, Cai M, Shen B, Fan C and Zhou X: Electroacupuncture at Zusanli regulates the pathological phenotype of inflammatory bowel disease by modulating the NLRP3 inflammasome pathway. Immun Inflamm Dis. 12:e13662024. View Article : Google Scholar : PubMed/NCBI