Inhibitors of the NLRP3 inflammasome pathway as promising therapeutic candidates for inflammatory diseases (Review)

Zhang,Xiaolu; Wang,Ziyu; Zheng,Yujia; Yu,Qun; Zeng,Miao; Bai,Liding; Yang,Lin; Guo,Maojuan; Jiang,Xijuan; Gan,Jiali

doi:10.3892/ijmm.2023.5238

April-2023 Volume 51 Issue 4

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April-2023 Volume 51 Issue 4

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Review Open Access

Inhibitors of the NLRP3 inflammasome pathway as promising therapeutic candidates for inflammatory diseases (Review)

Authors:
- Xiaolu Zhang
- Ziyu Wang
- Yujia Zheng
- Qun Yu
- Miao Zeng
- Liding Bai
- Lin Yang
- Maojuan Guo
- Xijuan Jiang
- Jiali Gan
View Affiliations / Copyright

Affiliations: School of Integrative Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, P.R. China, College of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, P.R. China

Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Article Number: 35
|
Published online on: March 21, 2023

https://doi.org/10.3892/ijmm.2023.5238
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Abstract

The inflammasome regulates innate immunity by serving as a signaling platform. The Nod‑like receptor protein 3 (NLRP3) inflammasome, equipped with NLRP3, the adaptor protein apoptosis‑associated speck‑like protein (ASC) and pro‑caspase‑1, is by far the most extensively studied and well‑characterized inflammasome. A variety of stimuli can activate the NLRP3 inflammasome. When activated, the NLRP3 protein recruits the adaptor ASC protein and activates pro‑caspase‑1, resulting in inflammatory cytokine maturation and secretion, which is associated with inflammation and pyroptosis. However, the aberrant activation of the NLRP3 inflammasome has been linked to various inflammatory diseases, including atherosclerosis, ischemic stroke, Alzheimer's disease, diabetes mellitus and inflammatory bowel disease. Therefore, the NLRP3 inflammasome has emerged as a promising therapeutic target for inflammatory diseases. In the present review, systematic searches were performed using ‘NLRP3 inhibitor(s)’ and ‘inflammatory disease(s)’ as key words. By browsing the literature from 2012 to 2022, 100 articles were retrieved, of which 35 were excluded as they were reviews, editorials, retracted or unavailable online, and 65 articles were included. According to the retrieved literature, the current understanding of NLRP3 inflammasome pathway activation in inflammatory diseases was summarize, and inhibitors of the NLRP3 inflammasome pathway targeting the NLRP3 protein and other inflammasome components or products were highlighted. Additionally, the present review briefly discusses the current novel efforts in clinical research.

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1	Fu C, Ye S, Liu Y and Li S: Role of CARD region of MDA5 gene in canine influenza virus infection. Viruses. 12:3072020. View Article : Google Scholar : PubMed/NCBI
2	Zhang Y and Okamoto CT: Nucleotide binding domain and leucine-rich repeat pyrin domain-containing protein 12: Characterization of its binding to hematopoietic cell kinase. Int J Biol Sci. 16:1507–1525. 2020. View Article : Google Scholar : PubMed/NCBI
3	Zhao C and Zhao W: NLRP3 inflammasome-A key player in antiviral responses. Front Immunol. 11:2112020. View Article : Google Scholar : PubMed/NCBI
4	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 : PubMed/NCBI
5	Zuo Y, Chen L, Gu H, He X, Ye Z, Wang Z, Shao Q and Xue C: GSDMD-mediated pyroptosis: A critical mechanism of diabetic nephropathy. Expert Rev Mol Med. 23:e232021. View Article : Google Scholar : PubMed/NCBI
6	Arioz BI, Tarakcioglu E, Olcum M and Genc S: The role of melatonin on NLRP3 inflammasome activation in diseases. Antioxidants (Basel). 10:10202021. View Article : Google Scholar : PubMed/NCBI
7	Vong CT, Tseng H, Yao P, Yu H, Wang S, Zhong Z and Wang Y: Specific NLRP3 inflammasome inhibitors: Promising therapeutic agents for inflammatory diseases. Drug Discov Today. 26:1394–1408. 2021. View Article : Google Scholar : PubMed/NCBI
8	Zeng W, Wu D, Sun Y, Suo Y, Yu Q, Zeng M, Gao Q, Yu B, Jiang X and Wang Y: The selective NLRP3 inhibitor MCC950 hinders atherosclerosis development by attenuating inflammation and pyroptosis in macrophages. Sci Rep. 11:193052021. View Article : Google Scholar : PubMed/NCBI
9	Feng YS, Tan ZX, Wang MM, Xing Y, Dong F and Zhang F: Inhibition of NLRP3 inflammasome: A prospective target for the treatment of ischemic stroke. Front Cell Neurosci. 14:1552020. View Article : Google Scholar : PubMed/NCBI
10	Holbrook JA, Jarosz-Griffiths HH, Caseley E, Lara-Reyna S, Poulter JA, Williams-Gray CH, Peckham D and McDermott MF: Neurodegenerative disease and the NLRP3 inflammasome. Front Pharmacol. 12:6432542021. View Article : Google Scholar : PubMed/NCBI
11	Ferreira NS, Bruder-Nascimento T, Pereira CA, Zanotto CZ, Prado DS, Silva JF, Rassi DM, Foss-Freitas MC, Alves-Filho JC, Carlos D, et al: NLRP3 inflammasome and mineralocorticoid receptors are associated with vascular dysfunction in type 2 diabetes mellitus. Cells. 8:15952019. View Article : Google Scholar : PubMed/NCBI
12	Jiang H, He H, Chen Y, Huang W, Cheng J, Ye J, Wang A, Tao J, Wang C, Liu Q, et al: Identification of a selective and direct NLRP3 inhibitor to treat inflammatory disorders. J Exp Med. 214:3219–3238. 2017. View Article : Google Scholar : PubMed/NCBI
13	Guarda G, Zenger M, Yazdi AS, Schroder K, Ferrero I, Menu P, Tardivel A, Mattmann C and Tschopp J: Differential expression of NLRP3 among hematopoietic cells. J Immunol. 186:2529–2534. 2011. View Article : Google Scholar : PubMed/NCBI
14	Zhong Y, Kinio A and Saleh M: Functions of NOD-like receptors in human diseases. Front Immunol. 4:3332013. View Article : Google Scholar : PubMed/NCBI
15	Park WJ and Han JS: Gryllus bimaculatus extract protects against lipopolysaccharide and palmitate-induced production of proinflammatory cytokines and inflammasome formation. Mol Med Rep. 23:2062021. View Article : Google Scholar : PubMed/NCBI
16	Flores-Costa R, Duran-Guell M, Casulleras M, Lopez-Vicario C, Alcaraz-Quiles J, Diaz A, Lozano JJ, Titos E, Hall K, Sarno R, et al: Stimulation of soluble guanylate cyclase exerts antiinflammatory actions in the liver through a VASP/NF-κB/NLRP3 inflammasome circuit. Proc Natl Acad Sci USA. 117:28263–28274. 2020. View Article : Google Scholar
17	Dowling JK and O'Neill LA: Biochemical regulation of the inflammasome. Crit Rev Biochem Mol. 47:424–443. 2012. View Article : Google Scholar
18	Ulland TK, Ferguson PJ and Sutterwala FS: Evasion of inflammasome activation by microbial pathogens. J Clin Invest. 125:469–477. 2015. View Article : Google Scholar : PubMed/NCBI
19	Trojan E, Tylek K, Leskiewicz M, Lason W, Brandenburg LO, Leopoldo M, Lacivita E and Basta-Kaim A: The N-Formyl peptide receptor 2 (FPR2) agonist MR-39 exhibits anti-inflammatory activity in LPS-stimulated organotypic hippocampal cultures. Cells. 10:15242021. View Article : Google Scholar : PubMed/NCBI
20	Ming SL, Zeng L, Guo YK, Zhang S, Li GL, Ma YX, Zhai YY, Chang WR, Yang L, Wang J, et al: The human-specific STING agonist G10 activates type I interferon and the NLRP3 inflammasome in porcine cells. Front Immunol. 11:5758182020. View Article : Google Scholar : PubMed/NCBI
21	Munoz-Planillo R, Kuffa P, Martinez-Colon G, Smith BL, Rajendiran TM and Nunez 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
22	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
23	He Y, Zeng MY, Yang D, Motro B and Nunez G: NEK7 is an essential mediator of NLRP3 activation downstream of potassium efflux. Nature. 530:354–357. 2016. View Article : Google Scholar : PubMed/NCBI
24	Maejima I, Takahashi A, Omori H, Kimura T, Takabatake Y, Saitoh T, Yamamoto A, Hamasaki M, Noda T, Isaka Y, et al: Autophagy sequesters damaged lysosomes to control lysosomal biogenesis and kidney injury. EMBO J. 32:2336–2347. 2013. View Article : Google Scholar : PubMed/NCBI
25	Otsuki T, Holian A and Di Gioacchino M: Immunological effects of environmental factors: Focus on the fibrous and particulated materials. J Immunol Res. 2014:6974382014. View Article : Google Scholar : PubMed/NCBI
26	Wang Y, Qin X and Paudel HK: Amyloid beta peptide promotes lysosomal degradation of clusterin via sortilin in hippocampal primary neurons. Neurobiol Dis. 103:78–88. 2017. View Article : Google Scholar : PubMed/NCBI
27	Ismael S, Ahmed HA, Adris T, Parveen K, Thakor P and Ishrat T: The NLRP3 inflammasome: A potential therapeutic target for traumatic brain injury. Neural Regen Res. 16:49–57. 2021. View Article : Google Scholar :
28	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 : PubMed/NCBI
29	Bauernfeind F, Bartok E, Rieger A, Franchi L, Nunez G and Hornung V: Cutting edge: Reactive oxygen species inhibitors block priming, but not activation, of the NLRP3 inflammasome. J Immunol. 187:613–617. 2011. View Article : Google Scholar : PubMed/NCBI
30	Wang C, Fu KK, Dai J, Lacey SD, Yao Y, Pastel G, Xu L, Zhang J and Hu L: Inverted battery design as ion generator for interfacing with biosystems. Nat Commun. 8:156092017. View Article : Google Scholar : PubMed/NCBI
31	Ma C, Liu S, Zhang S, Xu T, Yu X, Gao Y, Zhai C, Li C, Lei C, Fan S, et al: Evidence and perspective for the role of the NLRP3 inflammasome signaling pathway in ischemic stroke and its therapeutic potential (Review). Int J Mol Med. 42:2979–2990. 2018.PubMed/NCBI
32	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
33	Zhong Z, Zhai Y, Liang S, Mori Y, Han R, Sutterwala FS and Qiao L: TRPM2 links oxidative stress to NLRP3 inflammasome activation. Nat Commun. 4:16112013. View Article : Google Scholar : PubMed/NCBI
34	Jo EK, Kim JK, Shin DM and Sasakawa C: Molecular mechanisms regulating NLRP3 inflammasome activation. Cell Mol Immunol. 13:148–159. 2016. View Article : Google Scholar :
35	Hosen MR, Goody PR, Zietzer A, Nickenig G and Jansen F: MicroRNAs as master regulators of atherosclerosis: From pathogenesis to novel therapeutic options. Antioxid Redox Sign. 33:621–644. 2020. View Article : Google Scholar
36	Saigusa R, Winkels H and Ley K: T cell subsets and functions in atherosclerosis. Nat Rev Cardiol. 17:387–401. 2020. View Article : Google Scholar : PubMed/NCBI
37	Martinet W, Coornaert I, Puylaert P and De Meyer G: Macrophage death as a pharmacological target in atherosclerosis. Front Pharmacol. 10:3062019. View Article : Google Scholar : PubMed/NCBI
38	Xu H, Jiang J, Chen W, Li W and Chen Z: Vascular macrophages in atherosclerosis. J Immunol Res. 2019:43547862019. View Article : Google Scholar : PubMed/NCBI
39	Ren XS, Tong Y, Ling L, Chen D, Sun HJ, Zhou H, Qi XH, Chen Q, Li YH, Kang YM and Zhu GQ: NLRP3 Gene deletion attenuates Angiotensin II-Induced phenotypic transformation of vascular smooth muscle cells and vascular remodeling. Cell Physiol Biochem. 44:2269–2280. 2017. View Article : Google Scholar : PubMed/NCBI
40	Wu X, Zhang H, Qi W, Zhang Y, Li J, Li Z, Lin Y, Bai X, Liu X, Chen X, et al: Nicotine promotes atherosclerosis via ROS-NLRP3-mediated endothelial cell pyroptosis. Cell Death Dis. 9:1712018. View Article : Google Scholar : PubMed/NCBI
41	Zhao Z, Wang X, Zhang R, Ma B, Niu S, Di X, Ni L and Liu C: Melatonin attenuates smoking-induced atherosclerosis by activating the Nrf2 pathway via NLRP3 inflammasomes in endothelial cells. Aging (Albany NY). 13:11363–11380. 2021. View Article : Google Scholar : PubMed/NCBI
42	Mehta S and Dhawan V: Exposure of cigarette smoke condensate activates NLRP3 inflammasome in THP-1 cells in a stage-specific manner: An underlying role of innate immunity in atherosclerosis. Cell Signal. 72:1096452020. View Article : Google Scholar : PubMed/NCBI
43	Mehta S, Srivastava N, Bhatia A and Dhawan V: Exposure of cigarette smoke condensate activates NLRP3 inflammasome in vitro and in vivo: A connotation of innate immunity and atherosclerosis. Int Immunopharmacol. 84:1065612020. View Article : Google Scholar : PubMed/NCBI
44	Keping Y, Yunfeng S, Pengzhuo X, Liang L, Chenhong X and Jinghua M: Sestrin1 inhibits oxidized low-density lipoprotein-induced activation of NLRP3 inflammasome in macrophages in a murine atherosclerosis model. Eur J Immunol. 50:1154–1166. 2020. View Article : Google Scholar : PubMed/NCBI
45	Ma Q, Yang Q, Chen J, Yu C, Zhang L, Zhou W and Chen M: Salvianolic acid A ameliorates early-stage atherosclerosis development by inhibiting NLRP3 inflammasome activation in zucker diabetic fatty rats. Molecules. 25:10892020. View Article : Google Scholar : PubMed/NCBI
46	Li W, Liu D, Xu J, Zha J, Wang C, An J, Xie Z and Qiao S: Astrocyte-Derived TNF-alpha-Activated platelets promote cerebral Ischemia/Reperfusion injury by regulating the RIP1/RIP3/AKT signaling pathway. Mol Neurobiol. 59:5734–5749. 2022. View Article : Google Scholar : PubMed/NCBI
47	Sun R, Peng M, Xu P, Huang F, Xie Y, Li J, Hong Y, Guo H, Liu Q and Zhu W: Low-density lipoprotein receptor (LDLR) regulates NLRP3-mediated neuronal pyroptosis following cerebral ischemia/reperfusion injury. J Neuroinflamm. 17:3302020. View Article : Google Scholar
48	Shimizu T, Smits R and Ikenaka K: Microglia-induced activation of non-canonical Wnt signaling aggravates neurodegeneration in demyelinating disorders. Mol Cell Biol. 36:2728–2741. 2016. View Article : Google Scholar : PubMed/NCBI
49	Ma DC, Zhang NN, Zhang YN and Chen HS: Kv1.3 channel blockade alleviates cerebral ischemia/reperfusion injury by reshaping M1/M2 phenotypes and compromising the activation of NLRP3 inflammasome in microglia. Exp Neurol. 332:1133992020. View Article : Google Scholar : PubMed/NCBI
50	Pozzo ED, Tremolanti C, Costa B, Giacomelli C, Milenkovic VM, Bader S, Wetzel CH, Rupprecht R, Taliani S, Settimo FD and Martini C: Microglial Pro-Inflammatory and Anti-Inflammatory phenotypes are modulated by translocator protein activation. Int J Mol Sci. 20:44672019. View Article : Google Scholar : PubMed/NCBI
51	Chen C, Ai Q, Chu S, Zhang Z, Zhou X, Luo P, Liu Y and Chen N: IMM-H004 protects against oxygen-glucose deprivation/reperfusion injury to BV2 microglia partly by modulating CKLF1 involved in microglia polarization. Int Immunopharmacol. 70:69–79. 2019. View Article : Google Scholar : PubMed/NCBI
52	Liu H, Wu X, Luo J, Zhao L, Li X, Guo H, Bai H, Cui W, Guo W, Feng D and Qu Y: Adiponectin peptide alleviates oxidative stress and NLRP3 inflammasome activation after cerebral ischemia-reperfusion injury by regulating AMPK/GSK-3β. Exp Neurol. 329:1133022020. View Article : Google Scholar
53	Zhao J, Piao X, Wu Y, Liang S, Han F, Liang Q, Shao S and Zhao D: Cepharanthine attenuates cerebral ischemia/reperfusion injury by reducing NLRP3 inflammasome-induced inflammation and oxidative stress via inhibiting 12/15-LOX signaling. Biomed Pharmacother. 127:1101512020. View Article : Google Scholar : PubMed/NCBI
54	Kaushal V, Koeberle PD, Wang Y and Schlichter LC: The Ca2+-activated K+ channel KCNN4/KCa3.1 contributes to microglia activation and nitric oxide-dependent neurodegeneration. J Neurosci. 27:234–244. 2007. View Article : Google Scholar : PubMed/NCBI
55	Ma DC, Zhang NN, Zhang YN and Chen HS: Salvianolic Acids for injection alleviates cerebral ischemia/reperfusion injury by switching M1/M2 phenotypes and inhibiting NLRP3 inflammasome/pyroptosis axis in microglia in vivo and in vitro. J Ethnopharmacol. 270:1137762021. View Article : Google Scholar : PubMed/NCBI
56	Li ZG, Shui SF, Han XW and Yan L: NLRP10 ablation protects against ischemia/reperfusion-associated brain injury by suppression of neuroinflammation. Exp Cell Res. 389:1119122020. View Article : Google Scholar : PubMed/NCBI
57	Cao X, Wang Y and Gao L: CHRFAM7A overexpression attenuates cerebral ischemia-reperfusion injury via inhibiting microglia pyroptosis mediated by the NLRP3/Caspase-1 pathway. Inflammation. 44:1023–1034. 2021. View Article : Google Scholar : PubMed/NCBI
58	Bellut M, Papp L, Bieber M, Kraft P, Stoll G and Schuhmann MK: NLPR3 inflammasome inhibition alleviates hypoxic endothelial cell death in vitro and protects blood-brain barrier integrity in murine stroke. Cell Death Dis. 13:202021. View Article : Google Scholar : PubMed/NCBI
59	Fu C, Zhang X, Zeng Z, Tian Y, Jin X, Wang F, Xu Z, Chen B, Zheng H and Liu X: Neuroprotective effects of qingnao dripping pills against cerebral ischemia via Inhibiting NLRP3 inflammasome signaling pathway: In vivo and in vitro. Front Pharmacol. 11:652020. View Article : Google Scholar : PubMed/NCBI
60	Denes A, Coutts G, Lenart N, Cruickshank SM, Pelegrin P, Skinner J, Rothwell N, Allan SM and Brough D: AIM2 and NLRC4 inflammasomes contribute with ASC to acute brain injury independently of NLRP3. Proc Natl Acad Sci USA. 112:4050–4055. 2015. View Article : Google Scholar : PubMed/NCBI
61	Severini C, Barbato C, Di Certo MG, Gabanella F, Petrella C, Di Stadio A, de Vincentiis M, Polimeni A, Ralli M and Greco A: Alzheimer's disease: New concepts on the role of autoimmunity and NLRP3 inflammasome in the pathogenesis of the disease. Curr Neuropharmacol. 19:498–512. 2021.
62	Lee YJ, Han SB, Nam SY, Oh KW and Hong JT: Inflammation and Alzheimer's disease. Arch Pharm Res. 33:1539–1556. 2010. View Article : Google Scholar : PubMed/NCBI
63	Li G, Dong Y, Liu D, Zou Z, Hao G, Gao X, Pan P and Liang G: NEK7 coordinates rapid neuroinflammation after subarachnoid hemorrhage in mice. Front Neurol. 11:5512020. View Article : Google Scholar : PubMed/NCBI
64	Liang S, Zhong Z, Kim SY, Uchiyama R, Roh YS, Matsushita H, Gottlieb RA and Seki E: Murine macrophage autophagy protects against alcohol-induced liver injury by degrading interferon regulatory factor 1 (IRF1) and removing damaged mitochondria. J Biol Chem. 294:12359–12369. 2019. View Article : Google Scholar : PubMed/NCBI
65	Cui W, Sun C, Ma Y, Wang S, Wang X and Zhang Y: Inhibition of TLR4 induces M2 microglial polarization and provides neuroprotection via the NLRP3 inflammasome in Alzheimer's disease. Front Neurosci. 14:4442020. View Article : Google Scholar : PubMed/NCBI
66	He XF, Xu JH, Li G, Li MY, Li LL, Pei Z, Zhang LY and Hu XQ: NLRP3-dependent microglial training impaired the clearance of amyloid-beta and aggravated the cognitive decline in Alzheimer's disease. Cell Death Dis. 11:8492020. View Article : Google Scholar : PubMed/NCBI
67	Ismael S, Wajidunnisa, Sakata K, McDonald MP, Liao FF and Ishrat T: ER stress associated TXNIP-NLRP3 inflammasome activation in hippocampus of human Alzheimer's disease. Neurochem Int. 148:1051042021. View Article : Google Scholar : PubMed/NCBI
68	Li L, Ismael S, Nasoohi S, Sakata K, Liao FF, McDonald MP and Ishrat T: Thioredoxin-interacting protein (TXNIP) associated NLRP3 inflammasome activation in human Alzheimer's disease brain. J Alzheimers Dis. 68:255–265. 2019. View Article : Google Scholar : PubMed/NCBI
69	Tang H and Harte M: Investigating markers of the NLRP3 inflammasome pathway in Alzheimer's disease: A human post-mortem study. Genes (Basel). 12:17532021. View Article : Google Scholar : PubMed/NCBI
70	Heneka MT, Kummer MP, Stutz A, Delekate A, Schwartz S, Vieira-Saecker A, Griep A, Axt D, Remus A, Tzeng TC, et al: NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice. Nature. 493:674–678. 2013. View Article : Google Scholar
71	Garcia-Serrano AM and Duarte J: Brain metabolism alterations in type 2 diabetes: What did we learn from diet-induced diabetes models? Front Neurosci. 14:2292020. View Article : Google Scholar : PubMed/NCBI
72	An X, Jin D, Duan L, Zhao S, Zhou R, Lian F and Tong X: Direct and indirect therapeutic effect of traditional Chinese medicine as an add-on for non-proliferative diabetic retinopathy: A systematic review and meta-analysis. Chin Med. 15:992020. View Article : Google Scholar : PubMed/NCBI
73	Omar SM, Musa IR, ElSouli A and Adam I: Prevalence, risk factors, and glycaemic control of type 2 diabetes mellitus in eastern Sudan: A community-based study. Ther Adv Endocrinol. 10:19061866492019.
74	Yu ZW, Zhang J, Li X, Wang Y, Fu YH and Gao XY: A new research hot spot: The role of NLRP3 inflammasome activation, a key step in pyroptosis, in diabetes and diabetic complications. Life Sci. 240:1171382020. View Article : Google Scholar
75	Wanrooy BJ, Kumar KP, Wen SW, Qin CX, Ritchie RH and Wong C: Distinct contributions of hyperglycemia and high-fat feeding in metabolic syndrome-induced neuroinflammation. J Neuroinflamm. 15:2932018. View Article : Google Scholar
76	Zhang H, Chen H, Wu X, Sun T, Fan M, Tong H, Zhu Y, Yin Z, Sun W, Zhang C, et al: Tetramethylpyrazine alleviates diabetes-induced high platelet response and endothelial adhesion via inhibiting NLRP3 inflammasome activation. Phytomedicine. 96:1538602022. View Article : Google Scholar
77	Zheng Q, Pan L and Ji Y: H₂S protects against diabetes-accelerated atherosclerosis by preventing the activation of NLRP3 inflammasome. J Biomed Res. 34:94–102. 2019. View Article : Google Scholar
78	Lian D, Liu J, Han R, Jin J, Zhu L, Zhang Y, Huang Y, Wang X, Xian S and Chen Y: Kakonein restores diabetes-induced endothelial junction dysfunction via promoting autophagy-mediated NLRP3 inflammasome degradation. J Cell Mol Med. 25:7169–7180. 2021. View Article : Google Scholar : PubMed/NCBI
79	Sharma A, Choi J, Stefanovic N, Al-Sharea A, Simpson DS, Mukhamedova N, Jandeleit-Dahm K, Murphy AJ, Sviridov D, Vince JE, et al: Specific NLRP3 inhibition protects against diabetes-associated atherosclerosis. Diabetes. 70:772–787. 2021. View Article : Google Scholar
80	Ward R, Li W, Abdul Y, Jackson L, Dong G, Jamil S, Filosa J, Fagan SC and Ergul A: NLRP3 inflammasome inhibition with MCC950 improves diabetes-mediated cognitive impairment and vasoneuronal remodeling after ischemia. Pharmacol Res. 142:237–250. 2019. View Article : Google Scholar : PubMed/NCBI
81	Amin FM, Abdelaziz RR, Hamed MF, Nader MA and Shehatou G: Dimethyl fumarate ameliorates diabetes-associated vascular complications through ROS-TXNIP-NLRP3 inflammasome pathway. Life Sci. 256:1178872020. View Article : Google Scholar : PubMed/NCBI
82	Lin HB, Wei GS, Li FX, Guo WJ, Hong P, Weng YQ, Zhang QQ, Xu SY, Liang WB, You ZJ, et al: Macrophage-NLRP3 inflammasome activation exacerbates cardiac dysfunction after ischemic stroke in a mouse model of diabetes. Neurosci Bull. 36:1035–1045. 2020. View Article : Google Scholar : PubMed/NCBI
83	Kim SR, Lee SG, Kim SH, Kim JH, Choi E, Cho W, Rim JH, Hwang I, Lee CJ, Lee M, et al: SGLT2 inhibition modulates NLRP3 inflammasome activity via ketones and insulin in diabetes with cardiovascular disease. Nat Commun. 11:21272020. View Article : Google Scholar : PubMed/NCBI
84	Dror E, Dalmas E, Meier DT, Wueest S, Thevenet J, Thienel C, Timper K, Nordmann TM, Traub S, Schulze F, et al: Postprandial macrophage-derived IL-1beta stimulates insulin, and both synergistically promote glucose disposal and inflammation. Nat Immunol. 18:283–292. 2017. View Article : Google Scholar : PubMed/NCBI
85	Burke SJ, Batdorf HM, Burk DH, Martin TM, Mendoza T, Stadler K, Alami W, Karlstad MD, Robson MJ, Blakely RD, et al: Pancreatic deletion of the interleukin-1 receptor disrupts whole body glucose homeostasis and promotes islet β-cell de-differentiation. Mol Metab. 14:95–107. 2018. View Article : Google Scholar : PubMed/NCBI
86	Yang M, Wang X, Han Y, Li C, Wei L, Yang J, Chen W, Zhu X and Sun L: Targeting the NLRP3 inflammasome in diabetic nephropathy. Curr Med Chem. 28:8810–8824. 2021. View Article : Google Scholar : PubMed/NCBI
87	Den Hartogh DJ, Gabriel A and Tsiani E: Antidiabetic properties of Curcumin II: Evidence from in vivo studies. Nutrients. 12:582019. View Article : Google Scholar : PubMed/NCBI
88	Oltean S, Coward R, Collino M and Baelde H: Diabetic nephropathy: Novel molecular mechanisms and therapeutic avenues. Biomed Res Int. 2017:31465242017. View Article : Google Scholar
89	Wang B, Dai Z, Gao Q, Liu Y, Gu G and Zheng H: Spop ameliorates diabetic nephropathy through restraining NLRP3 inflammasome. Biochem Bioph Res Commun. 594:131–138. 2022. View Article : Google Scholar
90	Tassetto M, Scialdone A, Solini A and Di Virgilio F: The P2X7 receptor: A promising pharmacological target in diabetic retinopathy. Int J Mol Sci. 22:71102021. View Article : Google Scholar : PubMed/NCBI
91	Li R, Chen L, Yao GM, Yan HL and Wang L: Effects of quercetin on diabetic retinopathy and its association with NLRP3 inflammasome and autophagy. Int J Ophthalmol. 14:42–49. 2021. View Article : Google Scholar : PubMed/NCBI
92	Lin HB, Lin YH, Zhang JY, Guo WJ, Ovcjak A, You ZJ, Feng ZP, Sun HS, Li FX and Zhang HF: NLRP3 inflammasome: A potential target in isoflurane pretreatment alleviates Stroke-induced retinal injury in diabetes. Front Cell Neurosci. 15:6974492021. View Article : Google Scholar : PubMed/NCBI
93	Shujun W, Huijie Z, Xia B and Hongjian W: Cerebral venous sinus thrombosis in patients with inflammatory bowel disease: A retrospective study. Sci Rep. 11:170042021. View Article : Google Scholar : PubMed/NCBI
94	Fu Y, Lee CH and Chi CC: Association of psoriasis with inflammatory bowel disease: A systematic review and Meta-analysis. JAMA Dermatol. 154:1417–1423. 2018. View Article : Google Scholar : PubMed/NCBI
95	Ginwala R, Bhavsar R, Chigbu DI, Jain P and Khan ZK: Potential role of flavonoids in treating chronic inflammatory diseases with a special focus on the anti-inflammatory activity of apigenin. Antioxidants (Basel). 8:352019. View Article : Google Scholar : PubMed/NCBI
96	Wang H and Ma YC: Role of NLRP1 and NLRP3 inflammasome signaling pathways in the immune mechanism of inflammatory bowel disease in children. Zhongguo Dang Dai Er Ke Za Zhi. 22:854–859. 2020.In Chinese. PubMed/NCBI
97	Zhou W, Liu X, Zhang X, Tang J, Li Z, Wang Q and Hu R: Oroxylin A inhibits colitis by inactivating NLRP3 inflammasome. Oncotarget. 8:58903–58917. 2017. View Article : Google Scholar : PubMed/NCBI
98	Zhang C, Qin J, Zhang S, Zhang N, Tan B, Siwko S, Zhang Y, Wang Q, Chen J, Qian M, et al: ADP/P2Y₁ aggravates inflammatory bowel disease through ERK5-mediated NLRP3 inflammasome activation. Mucosal Immunol. 13:931–945. 2020. View Article : Google Scholar : PubMed/NCBI
99	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 Immun. 147:267–279. 2021. View Article : Google Scholar
100	Chen X, Liu G, Yuan Y, Wu G, Wang S and Yuan L: NEK7 interacts with NLRP3 to modulate the pyroptosis in inflammatory bowel disease via NF-κB signaling. Cell Death Dis. 10:9062019. View Article : Google Scholar
101	Ma X, Di Q, Li X, Zhao X, Zhang R, Xiao Y, Li X, Wu H, Tang H, Quan J, et al: Munronoid I ameliorates DSS-induced mouse colitis by inhibiting NLRP3 inflammasome activation and pyroptosis via modulation of NLRP3. Front Immunol. 13:8531942022. View Article : Google Scholar : PubMed/NCBI
102	Jiang Q, Li W, Zhu X, Yu L, Lu Z, Liu Y, Ma B and Cheng L: Estrogen receptor β alleviates inflammatory lesions in a rat model of inflammatory bowel disease via down-regulating P2X7R expression in macrophages. Int J Biochem Cell Biol. 139:1060682021. View Article : Google Scholar
103	Sang H, Xie Y, Su X, Zhang M, Zhang Y, Liu K and Wang J: Mushroom Bulgaria Inquinans modulates host immunological response and gut microbiota in mice. Front Nutr. 7:1442020. View Article : Google Scholar : PubMed/NCBI
104	Liu Z and Wang H: Probiotics alleviate inflammatory bowel disease in mice by regulating intestinal microorganisms-bile acid-NLRP3 inflammasome pathway. Acta Biochim Pol. 68:687–693. 2021.PubMed/NCBI
105	Dinarello CA, Simon A and van der Meer JW: Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases. Nat Rev Drug Discov. 11:633–652. 2012. View Article : Google Scholar : PubMed/NCBI
106	Liu M, Saredy J, Zhang R, Shao Y, Sun Y, Yang WY, Wang J, Liu L, Drummer CT, Johnson C, et al: Approaching inflammation paradoxes-proinflammatory cytokine blockages induce inflammatory regulators. Front Immunol. 11:5543012020. View Article : Google Scholar : PubMed/NCBI
107	Liu J, Zhang N, Zhang M, Yin H, Zhang X, Wang X, Wang X and Zhao Y: N-acetylserotonin alleviated the expression of interleukin-1beta in retinal ischemia-reperfusion rats via the TTLR4/NF-κB/NLRP3 pathway. Exp Eye Res. 208:1085952021. View Article : Google Scholar
108	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 : PubMed/NCBI
109	Fernandes-Alnemri T, Kang S, Anderson C, Sagara J, Fitzgerald KA and Alnemri ES: Cutting edge: TLR signaling licenses IRAK1 for rapid activation of the NLRP3 inflammasome. J Immunol. 191:3995–3999. 2013. View Article : Google Scholar : PubMed/NCBI
110	Yang J, Wise L and Fukuchi KI: TLR4 cross-talk with NLRP3 inflammasome and complement signaling pathways in Alzheimer's disease. Front Immunol. 11:7242020. View Article : Google Scholar : PubMed/NCBI
111	Matsunaga N, Tsuchimori N, Matsumoto T and Ii M: TAK-242 (resatorvid), a small-molecule inhibitor of Toll-like receptor (TLR) 4 signaling, binds selectively to TLR4 and interferes with interactions between TLR4 and its adaptor molecules. Mol Pharmacol. 79:34–41. 2011. View Article : Google Scholar
112	Plunk MA, Alaniz A, Olademehin OP, Ellington TL, Shuford KL and Kane RR: Design and catalyzed activation of Tak-242 prodrugs for localized inhibition of TLR4-induced inflammation. Acs Med Chem Lett. 11:141–146. 2020. View Article : Google Scholar : PubMed/NCBI
113	Feng Y, Gao J, Cui Y, Li M, Li R, Cui C and Cui J: Neuroprotective effects of resatorvid against traumatic brain injury in rat: Involvement of neuronal autophagy and TLR4 signaling pathway. Cell Mol Neurobiol. 37:155–168. 2017. View Article : Google Scholar
114	Karimy JK, Reeves BC and Kahle KT: Targeting TLR4-dependent inflammation in post-hemorrhagic brain injury. Expert Opin Ther Tar. 24:525–533. 2020. View Article : Google Scholar
115	Liu Y, Dai Y, Li Q, Chen C, Chen H, Song Y, Hua F and Zhang Z: Beta-amyloid activates NLRP3 inflammasome via TLR4 in mouse microglia. Neurosci Lett. 736:1352792020. View Article : Google Scholar : PubMed/NCBI
116	Hong YP, Yu J, Su YR, Mei FC, Li M, Zhao KL, Zhao L, Deng WH, Chen C and Wang WX: High-fat diet aggravates acute pancreatitis via TLR4-mediated necroptosis and inflammation in rats. Oxid Med Cell Longev. 2020:81727142020. View Article : Google Scholar : PubMed/NCBI
117	Xu M, Ye Z, Zhao X, Guo H, Gong X and Huang R: Deficiency of tenascin-C attenuated cardiac injury by inactivating TLR4/NLRP3/caspase-1 pathway after myocardial infarction. Cell Signal. 86:1100842021. View Article : Google Scholar : PubMed/NCBI
118	Huang X, Shen H, Liu Y, Qiu S and Guo Y: Fisetin attenuates periodontitis through FGFR1/TLR4/NLRP3 inflammasome pathway. Int Immunopharmacol. 95:1075052021. View Article : Google Scholar : PubMed/NCBI
119	Zhu Y, Zhu WP, Li W, Zhang HT, Chen BH, Ding A, Yang H and Zhang H: Implications of EET in renal ischemia/reperfusion by regulating NLRP3 expression and pyroptosis. Zhonghua Yi Xue Za Zhi. 100:779–784. 2020.In Chinese. PubMed/NCBI
120	Xu Q, Wang M, Guo H, Liu H, Zhang G, Xu C and Chen H: Emodin alleviates severe acute pancreatitis-associated acute lung injury by inhibiting the cold-inducible RNA-binding protein (CIRP)-mediated activation of the NLRP3/IL-1β/CXCL1 signaling. Front Pharmacol. 12:6553722021. View Article : Google Scholar
121	Pierce JW, Schoenleber R, Jesmok G, Best J, Moore SA, Collins T and Gerritsen ME: Novel inhibitors of cytokine-induced IkappaBalpha phosphorylation and endothelial cell adhesion molecule expression show anti-inflammatory effects in vivo. J Biol Chem. 272:21096–21103. 1997. View Article : Google Scholar : PubMed/NCBI
122	Irrera N, Vaccaro M, Bitto A, Pallio G, Pizzino G, Lentini M, Arcoraci V, Minutoli L, Scuruchi M, Cutroneo G, et al: BAY 11-7082 inhibits the NF-κB and NLRP3 inflammasome pathways and protects against IMQ-induced psoriasis. Clin Sci (Lond). 131:487–498. 2017.
123	Chen X, Wang Y, Yao N and Lin Z: Immunoproteasome modulates NLRP3 inflammasome-mediated neuroinflammation under cerebral ischaemia and reperfusion conditions. J Cell Mol Med. 26:462–474. 2022. View Article : Google Scholar
124	Lang L, Xu B, Yuan J, Li S, Lian S, Chen Y, Guo J and Yang H: GABA-mediated activated microglia induce neuroinflammation in the hippocampus of mice following cold exposure through the NLRP3 inflammasome and NF-κB signaling pathways. Int Immunopharmacol. 89:1069082020. View Article : Google Scholar
125	Gan HT, Chen YQ and Ouyang Q: Sulfasalazine inhibits activation of nuclear factor-kappaB in patients with ulcerative colitis. J Gastroen Hepatol. 20:1016–1024. 2005. View Article : Google Scholar
126	Hafez HM, Ibrahim MA, Yehia AW, Gad AA, Mohammed NAHS and Abdel-Gaber SA: Protective effect of mirtazapine against acetic acid-induced ulcerative colitis in rats: Role of NLRP3 inflammasome pathway. Int Immunopharmacol. 101:1081742021. View Article : Google Scholar : PubMed/NCBI
127	Ullah H, Saba E, Lee YY, Hong SB, Hyun SH, Kwak YS, Park CK, Kim SD and Rhee MH: Restorative effects of Rg3-enriched Korean Red Ginseng and Persicaria tinctoria extract on oxazolone-induced ulcerative colitis in mice. J Ginseng Res. 46:628–635. 2022. View Article : Google Scholar : PubMed/NCBI
128	Zhang Y and Shi Y: Intracellular potassium ion measurements by inductively coupled plasma optical emission spectrometer (ICP-OES). Methods Mol Biol. 2459:85–92. 2022. View Article : Google Scholar : PubMed/NCBI
129	Leu WJ, Chu JC, Hsu JL, Du CM, Jiang YH, Hsu LC, Huang WJ and Guh JH: Chalcones display anti-NLRP3 inflammasome activity in macrophages through inhibition of both priming and activation steps-structure-activity-relationship and mechanism studies. Molecules. 25:59602020. View Article : Google Scholar : PubMed/NCBI
130	Li Q, Feng H, Wang H, Wang Y, Mou W, Xu G, Zhang P, Li R, Shi W, Wang Z, et al: Licochalcone B specifically inhibits the NLRP3 inflammasome by disrupting NEK7-NLRP3 interaction. EMBO Rep. 23:e534992022. View Article : Google Scholar
131	Abais JM, Xia M, Zhang Y, Boini KM and Li PL: Redox regulation of NLRP3 inflammasomes: ROS as trigger or effector? Antioxid Redox Sign. 22:1111–1129. 2015. View Article : Google Scholar
132	Lan XF, Zhang XJ, Lin YN, Wang Q, Xu HJ, Zhou LN, Chen PL and Li QY: Estradiol regulates Txnip and prevents intermittent hypoxia-induced vascular injury. Sci Rep. 7:103182017. View Article : Google Scholar : PubMed/NCBI
133	Zhao Y, Guo Q, Zhu Q, Tan R, Bai D, Bu X, Lin B, Zhao K, Pan C, Chen H, et al: Flavonoid VI-16 protects against DSS-induced colitis by inhibiting Txnip-dependent NLRP3 inflammasome activation in macrophages via reducing oxidative stress. Mucosal Immunol. 12:1150–1163. 2019. View Article : Google Scholar : PubMed/NCBI
134	Al KH, Brown LJ, Hossain KR, Hudson AL, Sinclair-Burton AA, Ng JP, Daniel EL, Hare JE, Cornell BA, Curmi PM, et al: Members of the chloride intracellular ion channel protein family demonstrate glutaredoxin-like enzymatic activity. PLoS One. 10:e1156992015. View Article : Google Scholar
135	Ye L, Zeng Q, Ling M, Ma R, Chen H, Lin F, Li Z and Pan L: Inhibition of IP3R/Ca2+ Dysregulation Protects mice from ventilator-induced lung injury via endoplasmic reticulum and mitochondrial pathways. Front Immunol. 12:7290942021. View Article : Google Scholar : PubMed/NCBI
136	Davis BK, Wen H and Ting JP: The inflammasome NLRs in immunity, inflammation, and associated diseases. Annu Rev Immunol. 29:707–735. 2011. View Article : Google Scholar : PubMed/NCBI
137	Dick MS, Sborgi L, Ruhl S, Hiller S and Broz P: ASC filament formation serves as a signal amplification mechanism for inflammasomes. Nat Commun. 7:119292016. View Article : Google Scholar : PubMed/NCBI
138	Duncan JA, Bergstralh DT, Wang Y, Willingham SB, Ye Z, Zimmermann AG and Ting JP: Cryopyrin/NALP3 binds ATP/dATP, is an ATPase, and requires ATP binding to mediate inflammatory signaling. Proc Natl Acad Sci USA. 104:8041–8046. 2007. View Article : Google Scholar : PubMed/NCBI
139	Wu D, Chen Y, Sun Y, Gao Q, Li H, Yang Z, Wang Y, Jiang X and Yu B: Target of MCC950 in inhibition of NLRP3 inflammasome activation: A literature review. Inflammation. 43:17–23. 2020. View Article : Google Scholar
140	Dempsey C, Rubio AA, Bryson KJ, Finucane O, Larkin C, Mills EL, Robertson A, Cooper MA, O'Neill L and Lynch MA: Inhibiting the NLRP3 inflammasome with MCC950 promotes non-phlogistic clearance of amyloid-beta and cognitive function in APP/PS1 mice. Brain Behav Immun. 61:306–316. 2017. View Article : Google Scholar
141	Coll RC, Robertson AA, Chae JJ, Higgins SC, Munoz-Planillo R, Inserra MC, Vetter I, Dungan LS, Monks BG, Stutz A, et al: A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nat Med. 21:248–255. 2015. View Article : Google Scholar : PubMed/NCBI
142	Gross CJ, Mishra R, Schneider KS, Medard G, Wettmarshausen J, Dittlein DC, Shi H, Gorka O, Koenig PA, Fromm S, et al: K⁺ Efflux-independent NLRP3 inflammasome activation by small molecules targeting mitochondria. Immunity. 45:761–773. 2016. View Article : Google Scholar
143	van der Heijden T, Kritikou E, Venema W, van Duijn J, van Santbrink PJ, Slutter B, Foks AC, Bot I and Kuiper J: NLRP3 inflammasome inhibition by MCC950 reduces atherosclerotic lesion development in apolipoprotein E-deficient Mice-brief report. Arterioscl Throm Vas. 37:1457–1461. 2017. View Article : Google Scholar
144	Perera AP, Fernando R, Shinde T, Gundamaraju R, Southam B, Sohal SS, Robertson A, Schroder K, Kunde D and Eri R: MCC950, a specific small molecule inhibitor of NLRP3 inflammasome attenuates colonic inflammation in spontaneous colitis mice. Sci Rep. 8:86182018. View Article : Google Scholar : PubMed/NCBI
145	Ye J, Li L, Wang M, Ma Q, Tian Y, Zhang Q, Liu J, Li B, Zhang B, Liu H, et al: Diabetes mellitus promotes the development of atherosclerosis: The role of NLRP3. Front Immunol. 13:9002542022. View Article : Google Scholar : PubMed/NCBI
146	Franke M, Bieber M, Kraft P, Weber A, Stoll G and Schuhmann MK: The NLRP3 inflammasome drives inflammation in ischemia/reperfusion injury after transient middle cerebral artery occlusion in mice. Brain Behav Immun. 92:223–233. 2021. View Article : Google Scholar
147	Zhai Y, Meng X, Ye T, Xie W, Sun G and Sun X: Inhibiting the NLRP3 inflammasome activation with MCC950 ameliorates diabetic encephalopathy in db/db Mice. Molecules. 23:5222018. View Article : Google Scholar : PubMed/NCBI
148	Zhang C, Zhu X, Li L, Ma T, Shi M, Yang Y and Fan Q: A small molecule inhibitor MCC950 ameliorates kidney injury in diabetic nephropathy by inhibiting NLRP3 inflammasome activation. Diabetes Metab Syndr Obes. 12:1297–1309. 2019. View Article : Google Scholar : PubMed/NCBI
149	Kuo LM, Kuo CY, Lin CY, Hung MF, Shen JJ and Hwang TL: Intracellular glutathione depletion by oridonin leads to apoptosis in hepatic stellate cells. Molecules. 19:3327–3344. 2014. View Article : Google Scholar : PubMed/NCBI
150	He H, Jiang H, Chen Y, Ye J, Wang A, Wang C, Liu Q, Liang G, Deng X, Jiang W, et al: Oridonin is a covalent NLRP3 inhibitor with strong anti-inflammasome activity. Nat Commun. 9:25502018. View Article : Google Scholar : PubMed/NCBI
151	Gao RF, Li X, Xiang HY, Yang H, Lv CY, Sun XL, Chen HZ, Gao Y, Yang JS, Luo W, et al: The covalent NLRP3-inflammasome inhibitor Oridonin relieves myocardial infarction induced myocardial fibrosis and cardiac remodeling in mice. Int Immunopharmacol. 90:1071332021. View Article : Google Scholar
152	Jia Y, Tong Y, Min L, Li Y and Cheng Y: Protective effects of oridonin against cerebral ischemia/reperfusion injury by inhibiting the NLRP3 inflammasome activation. Tissue Cell. 71:1015142021. View Article : Google Scholar : PubMed/NCBI
153	Yan C, Yan H, Mao J, Liu Y, Xu L, Zhao H, Shen J, Cao Y, Gao Y, Li K, et al: Neuroprotective effect of oridonin on traumatic brain injury via inhibiting NLRP3 inflammasome in experimental mice. Front Neurosci. 14:5571702020. View Article : Google Scholar : PubMed/NCBI
154	Liang L, Zheng Y, Xie Y, Xiao L and Wang G: Oridonin ameliorates insulin resistance partially through inhibition of inflammatory response in rats subjected to chronic unpredictable mild stress. Int Immunopharmacol. 91:1072982021. View Article : Google Scholar : PubMed/NCBI
155	Marchetti C, Swartzwelter B, Koenders MI, Azam T, Tengesdal IW, Powers N, de Graaf DM, Dinarello CA and Joosten L: NLRP3 inflammasome inhibitor OLT1177 suppresses joint inflammation in murine models of acute arthritis. Arthritis Res Ther. 20:1692018. View Article : Google Scholar : PubMed/NCBI
156	Jankowsky JL, Fadale DJ, Anderson J, Xu GM, Gonzales V, Jenkins NA, Copeland NG, Lee MK, Younkin LH, Wagner SL, et al: Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: Evidence for augmentation of a 42-specific gamma secretase. Hum Mol Genet. 13:159–170. 2004. View Article : Google Scholar
157	Marchetti C, Swartzwelter B, Gamboni F, Neff CP, Richter K, Azam T, Carta S, Tengesdal I, Nemkov T, D'Alessandro A, et al: OLT1177, a β-sulfonyl nitrile compound, safe in humans, inhibits the NLRP3 inflammasome and reverses the metabolic cost of inflammation. Proc Natl Acad Sci USA. 115:E1530–E1539. 2018. View Article : Google Scholar
158	Lonnemann N, Hosseini S, Marchetti C, Skouras DB, Stefanoni D, D'Alessandro A, Dinarello CA and Korte M: The NLRP3 inflammasome inhibitor OLT1177 rescues cognitive impairment in a mouse model of Alzheimer's disease. Proc Natl Acad Sci USA. 117:32145–32154. 2020. View Article : Google Scholar : PubMed/NCBI
159	Sanchez-Fernandez A, Skouras DB, Dinarello CA and Lopez-Vales R: OLT1177 (Dapansutrile), a selective NLRP3 inflammasome inhibitor, ameliorates experimental autoimmune encephalomyelitis pathogenesis. Front Immunol. 10:25782019. View Article : Google Scholar : PubMed/NCBI
160	Oizumi T, Mayanagi T, Toya Y, Sugai T, Matsumoto T and Sobue K: NLRP3 Inflammasome inhibitor OLT1177 suppresses onset of inflammation in mice with dextran sulfate sodium-induced colitis. Digest Dis Sci. 67:2912–2921. 2022. View Article : Google Scholar
161	Toldo S, Mauro AG, Cutter Z, Van Tassell BW, Mezzaroma E, Del BM, Prestamburgo A, Potere N and Abbate A: The NLRP3 inflammasome inhibitor, OLT1177 (Dapansutrile), reduces infarct size and preserves contractile function after ischemia reperfusion injury in the mouse. J Cardiovasc Pharm. 73:215–222. 2019. View Article : Google Scholar
162	Shi Y, Lv Q, Zheng M, Sun H and Shi F: NLRP3 inflammasome inhibitor INF39 attenuated NLRP3 assembly in macrophages. Int Immunopharmacol. 92:1073582021. View Article : Google Scholar : PubMed/NCBI
163	Cocco M, Pellegrini C, Martinez-Banaclocha H, Giorgis M, Marini E, Costale A, Miglio G, Fornai M, Antonioli L, Lopez-Castejon G, et al: Development of an acrylate derivative targeting the NLRP3 inflammasome for the treatment of inflammatory bowel disease. J Med Chem. 60:3656–3671. 2017. View Article : Google Scholar : PubMed/NCBI
164	Pu Z, Han C, Zhang W, Xu M, Wu Z, Liu Y, Wu M, Sun H and Xie H: Systematic understanding of the mechanism and effects of Arctigenin attenuates inflammation in dextran sulfate sodium-induced acute colitis through suppression of NLRP3 inflammasome by SIRT1. Am J Transl Res. 11:3992–4009. 2019.PubMed/NCBI
165	Pellegrini C, Fornai M, Colucci R, Benvenuti L, D'Antongiovanni V, Natale G, Fulceri F, Giorgis M, Marini E, Gastaldi S, et al: A Comparative study on the efficacy of NLRP3 inflammasome signaling inhibitors in a Pre-clinical model of bowel inflammation. Front Pharmacol. 9:14052018. View Article : Google Scholar : PubMed/NCBI
166	Huang Y, Jiang H, Chen Y, Wang X, Yang Y, Tao J, Deng X, Liang G, Zhang H, Jiang W, et al: Tranilast directly targets NLRP3 to treat inflammasome-driven diseases. EMBO Mol Med. 10:e86892018. View Article : Google Scholar : PubMed/NCBI
167	Saeedi-Boroujeni A, Mahmoudian-Sani MR, Nashibi R, Houshmandfar S, Tahmaseby GS and Khodadadi A: Tranilast: A potential anti-Inflammatory and NLRP3 inflammasome inhibitor drug for COVID-19. Immunopharm Immunot. 43:247–258. 2021. View Article : Google Scholar
168	Cao J and Peng Q: NLRP3 inhibitor Tranilast attenuates gestational diabetes mellitus in a genetic mouse model. Drugs R D. 22:105–112. 2022. View Article : Google Scholar : PubMed/NCBI
169	Chen S, Wang Y, Pan Y, Liu Y, Zheng S, Ding K, Mu K, Yuan Y, Li Z, Song H, et al: Novel role for Tranilast in regulating NLRP3 ubiquitination, vascular inflammation, and atherosclerosis. J Am Heart Assoc. 9:e155132020. View Article : Google Scholar
170	Shen K, Jiang W, Zhang C, Cai L, Wang Q, Yu H, Tang Z, Gu Z and Chen B: Molecular mechanism of a specific NLRP3 inhibitor to alleviate seizure severity induced by pentylenetetrazole. Curr Mol Pharmacol. 14:579–586. 2021. View Article : Google Scholar
171	Marchetti C, Toldo S, Chojnacki J, Mezzaroma E, Liu K, Salloum FN, Nordio A, Carbone S, Mauro AG, Das A, et al: Pharmacologic inhibition of the NLRP3 inflammasome preserves cardiac function after ischemic and nonischemic injury in the mouse. J Cardiovasc Pharm. 66:1–8. 2015. View Article : Google Scholar
172	Kuwar R, Rolfe A, Di L, Xu H, He L, Jiang Y, Zhang S and Sun D: A novel small molecular NLRP3 inflammasome inhibitor alleviates neuroinflammatory response following traumatic brain injury. J Neuroinflamm. 16:812019. View Article : Google Scholar
173	Kuwar R, Rolfe A, Di L, Blevins H, Xu Y, Sun X, Bloom GS, Zhang S and Sun D: A novel inhibitor targeting NLRP3 inflammasome reduces neuropathology and improves cognitive function in Alzheimer's disease transgenic mice. J Alzheimers Dis. 82:1769–1783. 2021. View Article : Google Scholar : PubMed/NCBI
174	Yin J, Zhao F, Chojnacki JE, Fulp J, Klein WL, Zhang S and Zhu X: NLRP3 Inflammasome inhibitor ameliorates amyloid pathology in a mouse model of Alzheimer's disease. Mol Neurobiol. 55:1977–1987. 2018. View Article : Google Scholar
175	Fulp J, He L, Toldo S, Jiang Y, Boice A, Guo C, Li X, Rolfe A, Sun D, Abbate A, et al: Structural insights of Benzenesulfonamide analogues as NLRP3 inflammasome inhibitors: Design, synthesis, and biological characterization. J Med Chem. 61:5412–5423. 2018. View Article : Google Scholar : PubMed/NCBI
176	He Y, Varadarajan S, Munoz-Planillo R, Burberry A, Nakamura Y and Nunez G: 3,4-methylenedioxy-β-nitrostyrene inhibits NLRP3 inflammasome activation by blocking assembly of the inflammasome. J Biol Chem. 289:1142–1150. 2014. View Article : Google Scholar
177	Juliana C, Fernandes-Alnemri T, Wu J, Datta P, Solorzano L, Yu JW, Meng R, Quong AA, Latz E, Scott CP, et al: Anti-inflammatory compounds parthenolide and Bay 11-7082 are direct inhibitors of the inflammasome. J Biol Chem. 285:9792–9802. 2010. View Article : Google Scholar : PubMed/NCBI
178	Shim DW, Shin WY, Yu SH, Kim BH, Ye SK, Koppula S, Won HS, Kang TB and Lee KH: BOT-4-one attenuates NLRP3 inflammasome activation: NLRP3 alkylation leading to the regulation of its ATPase activity and ubiquitination. Sci Rep. 7:150202017. View Article : Google Scholar : PubMed/NCBI
179	Zheng D, Liwinski T and Elinav E: Inflammasome activation and regulation: Toward a better understanding of complex mechanisms. Cell Discov. 6:362020. View Article : Google Scholar : PubMed/NCBI
180	Li Y, Niu X, Xu H, Li Q, Meng L, He M, Zhang J and Zhang Z and Zhang Z: VX-765 attenuates atherosclerosis in ApoE deficient mice by modulating VSMCs pyroptosis. Exp Cell Res. 389:1118472020. View Article : Google Scholar : PubMed/NCBI
181	Zhang Z, Bai H, Ma X, Shen M, Li R, Qiu D, Li S and Gao L: Blockade of the NLRP3/caspase-1 axis attenuates ketamine-induced hippocampus pyroptosis and cognitive impairment in neonatal rats. J Neuroinflamm. 18:2392021. View Article : Google Scholar
182	Liang Y, Song P, Chen W, Xie X, Luo R, Su J, Zhu Y, Xu J, Liu R, Zhu P, et al: Inhibition of Caspase-1 Ameliorates Ischemia-Associated Blood-Brain barrier dysfunction and integrity by suppressing pyroptosis activation. Front Cell Neurosci. 14:5406692020. View Article : Google Scholar
183	Gu L, Sun M, Li R, Zhang X, Tao Y, Yuan Y, Luo X and Xie Z: Didymin suppresses microglia pyroptosis and neuroinflammation through the Asc/Caspase-1/GSDMD pathway following experimental intracerebral hemorrhage. Front Immunol. 13:8105822022. View Article : Google Scholar : PubMed/NCBI
184	Tian DD, Wang M, Liu A, Gao MR, Qiu C, Yu W, Wang WJ, Zhang K, Yang L, Jia YY, et al: Antidepressant effect of paeoniflorin is through inhibiting pyroptosis CASP-11/GSDMD pathway. Mol Neurobiol. 58:761–776. 2021. View Article : Google Scholar
185	Wang F, Liang Q, Ma Y, Sun M, Li T, Lin L, Sun Z and Duan J: Silica nanoparticles induce pyroptosis and cardiac hypertrophy via ROS/NLRP3/Caspase-1 pathway. Free Radical Bio Med. 182:171–181. 2022. View Article : Google Scholar
186	Xu S, Li X, Liu Y, Xia Y, Chang R and Zhang C: Inflammasome inhibitors: Promising therapeutic approaches against cancer. J Hematol Oncol. 12:642019. View Article : Google Scholar : PubMed/NCBI
187	Wang F, Li G, Ning J, Chen L, Xu H, Kong X, Bu J, Zhao W, Li Z, Wang X, et al: Alcohol accumulation promotes esophagitis via pyroptosis activation. Int J Biol Sci. 14:1245–1255. 2018. View Article : Google Scholar : PubMed/NCBI
188	Qiu Z, He Y, Ming H, Lei S, Leng Y and Xia ZY: Lipopolysaccharide (LPS) aggravates high glucose- and Hypoxia/Reoxygenation-induced injury through activating ROS-dependent NLRP3 inflammasome-mediated pyroptosis in H9C2 Cardiomyocytes. J Diabetes Res. 2019:81518362019. View Article : Google Scholar : PubMed/NCBI
189	Liang H, Sun Y, Gao A, Zhang N, Jia Y, Yang S, Na M, Liu H, Cheng X, Fang X, et al: Ac-YVAD-cmk improves neurological function by inhibiting caspase-1-mediated inflammatory response in the intracerebral hemorrhage of rats. Int Immunopharmacol. 75:1057712019. View Article : Google Scholar : PubMed/NCBI
190	Pan P, Shen M, Yu Z, Ge W, Chen K, Tian M, Xiao F, Wang Z, Wang J, Jia Y, et al: SARS-CoV-2 N protein promotes NLRP3 inflammasome activation to induce hyperinflammation. Nat Commun. 12:46642021. View Article : Google Scholar : PubMed/NCBI
191	Zheng X, Chen W, Gong F, Chen Y and Chen E: The role and mechanism of pyroptosis and potential therapeutic targets in sepsis: A review. Front Immunol. 12:7119392021. View Article : Google Scholar : PubMed/NCBI
192	Liu W, Guo W, Zhu Y, Peng S, Zheng W, Zhang C, Shao F, Zhu Y, Hang N, Kong L, et al: Targeting Peroxiredoxin 1 by a Curcumin analogue, AI-44, inhibits NLRP3 inflammasome activation and attenuates lipopolysaccharide-induced sepsis in mice. J Immunol. 201:2403–2413. 2018. View Article : Google Scholar : PubMed/NCBI
193	Liu W, Guo W, Wu J, Luo Q, Tao F, Gu Y, Shen Y, Li J, Tan R, Xu Q and Sun Y: A novel benzo[d]imidazole derivate prevents the development of dextran sulfate sodium-induced murine experimental colitis via inhibition of NLRP3 inflammasome. Biochem Pharmacol. 85:1504–1512. 2013. View Article : Google Scholar : PubMed/NCBI
194	Sborgi L, Ruhl S, Mulvihill E, Pipercevic J, Heilig R, Stahlberg H, Farady CJ, Muller DJ, Broz P and Hiller S: GSDMD membrane pore formation constitutes the mechanism of pyroptotic cell death. EMBO J. 35:1766–1778. 2016. View Article : Google Scholar : PubMed/NCBI
195	Shi J, Zhao Y, Wang K, Shi X, Wang Y, Huang H, Zhuang Y, Cai T, Wang F and Shao F: Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature. 526:660–665. 2015. View Article : Google Scholar : PubMed/NCBI
196	Liu Z, Gan L, Xu Y, Luo D, Ren Q, Wu S and Sun C: Melatonin alleviates inflammasome-induced pyroptosis through inhibiting NF-κB/GSDMD signal in mice adipose tissue. J Pineal Res. 63:2017. View Article : Google Scholar
197	Sun L, Wang H, Wang Z, He S, Chen S, Liao D, Wang L, Yan J, Liu W, Lei X and Wang X: Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase. Cell. 148:213–227. 2012. View Article : Google Scholar : PubMed/NCBI
198	Rathkey JK, Zhao J, Liu Z, Chen Y, Yang J, Kondolf HC, Benson BL, Chirieleison SM, Huang AY, Dubyak GR, et al: Chemical disruption of the pyroptotic pore-forming protein gasdermin D inhibits inflammatory cell death and sepsis. Sci Immunol. 3:eaat27382018. View Article : Google Scholar : PubMed/NCBI
199	Han C, Yang Y, Guan Q, Zhang X, Shen H, Sheng Y, Wang J, Zhou X, Li W, Guo L, et al: New mechanism of nerve injury in Alzheimer's disease: β-amyloid-induced neuronal pyroptosis. J Cell Mol Med. 24:8078–8090. 2020. View Article : Google Scholar : PubMed/NCBI
200	Teng JF, Mei QB, Zhou XG, Tang Y, Xiong R, Qiu WQ, Pan R, Law BY, Wong VK, Yu CL, et al: Polyphyllin VI induces Caspase-1-mediated Pyroptosis via the induction of ROS/NF-κB/NLRP3/GSDMD signal axis in Non-small cell lung cancer. Cancers (Basel). 12:1932020. View Article : Google Scholar
201	Guo W, Chen S, Li C, Xu J and Wang L: Application of Disulfiram and its metabolites in treatment of inflammatory disorders. Front Pharmacol. 12:7950782021. View Article : Google Scholar
202	Wu J, Zhang J, Zhao J, Chen S, Zhou T and Xu J: Treatment of severe acute pancreatitis and related lung injury by targeting gasdermin D-mediated pyroptosis. Front Cell Dev Biol. 9:7801422021. View Article : Google Scholar : PubMed/NCBI
203	Pandeya A, Li L, Li Z and Wei Y: Gasdermin D (GSDMD) as a new target for the treatment of infection. Medchemcomm. 10:660–667. 2019. View Article : Google Scholar : PubMed/NCBI
204	Hu JJ, Liu X, Xia S, Zhang Z, Zhang Y, Zhao J, Ruan J, Luo X, Lou X, Bai Y, et al: FDA-approved disulfiram inhibits pyroptosis by blocking gasdermin D pore formation. Nat Immunol. 21:736–745. 2020. View Article : Google Scholar : PubMed/NCBI
205	Zhou Q, Wang W, Yang F, Wang H, Zhao X, Zhou Y, Fu P and Xu Y: Disulfiram suppressed Peritendinous fibrosis through inhibiting macrophage accumulation and its pro-inflammatory properties in tendon bone healing. Front Bioeng Biotech. 10:8239332022. View Article : Google Scholar
206	Yan H, Yang H, Wang L, Sun X, Han L, Cong P, Chen X, Lu D and Che C: Disulfiram inhibits IL-1β secretion and inflammatory cells recruitment in Aspergillus fumigatus keratitis. Int Immunopharmacol. 102:1084012022. View Article : Google Scholar
207	Cattani-Cavalieri I, Da MVH, Moraes JA, Brito-Gitirana L, Romana-Souza B, Schmidt M and Valenca SS: Dimethyl fumarate attenuates lung inflammation and oxidative stress induced by chronic exposure to diesel exhaust particles in mice. Int J Mol Sci. 21:96582020. View Article : Google Scholar : PubMed/NCBI
208	Humphries F, Shmuel-Galia L, Ketelut-Carneiro N, Li S, Wang B, Nemmara VV, Wilson R, Jiang Z, Khalighinejad F, Muneeruddin K, et al: Succination inactivates gasdermin D and blocks pyroptosis. Science. 369:1633–1637. 2020. View Article : Google Scholar : PubMed/NCBI
209	Muhammad JS, Jayakumar MN, Elemam NM, Venkatachalam T, Raju TK, Hamoudi RA and Maghazachi AA: Gasdermin D Hypermethylation inhibits pyroptosis and LPS-Induced IL-1β release from NK92 cells. Immunotargets Ther. 8:29–41. 2019. View Article : Google Scholar :
210	Xia L, Liu L, Cai Y, Zhang Y, Tong F, Wang Q, Ding J and Wang X: Inhibition of Gasdermin D-mediated pyroptosis attenuates the severity of seizures and astroglial damage in kainic Acid-induced epileptic mice. Front Pharmacol. 12:7516442021. View Article : Google Scholar
211	Sohn E, Kim J, Kim CS, Jo K and Kim JS: Osteomeles schwerinae extract prevents diabetes-induced renal injury in spontaneously diabetic Torii rats. Evid Based Complement Alternat Med. 2018:68242152018. View Article : Google Scholar : PubMed/NCBI
212	Soma J, Sugawara T, Huang YD, Nakajima J and Kawamura M: Tranilast slows the progression of advanced diabetic nephropathy. Nephron. 92:693–698. 2002. View Article : Google Scholar : PubMed/NCBI
213	Soma J, Sato K, Saito H and Tsuchiya Y: Effect of Tranilast in early-stage diabetic nephropathy. Nephrol Dial Transpl. 21:2795–2799. 2006. View Article : Google Scholar
214	Kosuga K, Tamai H, Ueda K, Hsu YS, Ono S, Tanaka S, Doi T, Myou-U W, Motohara S and Uehata H: Effectiveness of Tranilast on restenosis after directional coronary atherectomy. Am Heart J. 134:712–718. 1997. View Article : Google Scholar : PubMed/NCBI
215	Wohlford GF, Van Tassell BW, Billingsley HE, Kadariya D, Canada JM, Carbone S, Mihalick VL, Bonaventura A, Vecchie A, Chiabrando JG, et al: Phase 1B, randomized, Double-blinded, dose escalation, single-center, repeat dose safety and pharmacodynamics study of the oral NLRP3 inhibitor dapansutrile in subjects with NYHA II-III systolic heart failure. J Cardiovasc Pharm. 77:49–60. 2020. View Article : Google Scholar
216	Kim M, Byun J, Chung Y, Lee SU, Park JE, Park W, Park JC, Ahn JS and Lee S: Reactive Oxygen species scavenger in acute intracerebral hemorrhage patients: A multicenter, randomized controlled trial. Stroke. 52:1172–1181. 2021. View Article : Google Scholar : PubMed/NCBI
217	Masnadi SK, Sotoudeh S, Masnadi SA, Moaddab SY, Nourpanah Z and Nikniaz Z: Effect of N-acetylcysteine on remission maintenance in patients with ulcerative colitis: A randomized, double-blind controlled clinical trial. Clin Res Hepatol Gas. 45:1015322021. View Article : Google Scholar
218	Reinhardt S, Stoye N, Luderer M, Kiefer F, Schmitt U, Lieb K and Endres K: Identification of disulfiram as a Secretase-modulating compound with beneficial effects on Alzheimer's disease hallmarks. Sci Rep. 8:13292018. View Article : Google Scholar : PubMed/NCBI
219	Yuan XZ, Sun S, Tan CC, Yu JT and Tan L: The role of ADAM10 in Alzheimer's disease. J Alzheimers Dis. 58:303–322. 2017. View Article : Google Scholar : PubMed/NCBI

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Inhibitors of the NLRP3 inflammasome pathway as promising therapeutic candidates for inflammatory diseases (Review)

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