Generic placeholder image

Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5230
ISSN (Online): 1875-614X

Perspective Article

Energy Provisioning and Inflammasome Activation: The Pivotal Role of AMPK in Sterile Inflammation and Associated Metabolic Disorders

Author(s): Akhila H. Shrungeswara and Mazhuvancherry K. Unnikrishnan*

Volume 20 , Issue 2 , 2021

Published on: 16 September, 2020

Page: [107 - 117] Pages: 11

DOI: 10.2174/1871523019666200916115034

Price: $65

Abstract

Background: Body defenses and metabolic processes probably co-evolved in such a way that rapid, energy-intensive acute inflammatory repair is functionally integrated with energy allocation in a starvation/ infection / injury-prone primitive environment. Disruptive metabolic surplus, aggravated by sedentary lifestyle induces chronic under-activation of AMPK, the master regulator of intracellular energy homeostasis. Sudden increase in chronic, dysregulated ‘sterile’ inflammatory disorders probably results from a shift towards calorie rich, sanitized, cushioned, injury/ infection free environment, repositioning inflammatory repair pathways towards chronic, non-microbial, ‘sterile’, ‘low grade’, and ‘parainflammation’. AMPK, (at the helm of energy provisioning) supervises the metabolic regulation of inflammasome activation, a common denominator in lifestyle disorders.

Discussion: In this review, we discuss various pathways linking AMPK under-activation and inflammasome activation. AMPK under-activation, the possible norm in energy-rich sedentary lifestyle, could be the central agency that stimulates inflammasome activation by multiple pathways such as 1: decreasing autophagy, and accumulation of intracellular DAMPs, (particulate crystalline molecules, advanced glycation end-products, oxidized lipids, etc.) 2: stimulating a glycolytic shift (pro-inflammatory) in metabolism, 3: promoting NF-kB activation and decreasing Nrf2 activation, 4: increasing reactive oxygen species (ROS) formation, Unfolded Protein Response (UPR) and Endoplasmic Reticulum (ER) stress.

Conclusion: The ‘inverse energy crisis’ associated with calorie-rich, sedentary lifestyle, advocates dietary and pharmacological interventions for treating chronic metabolic disorders by overcoming / reversing AMPK under-activation.

Keywords: Inflammasome, AMPK, inflammation, metabolic disorders, inflammatory signals, sterile.

Next »
Graphical Abstract
[1]
Swanson, K.V.; Deng, M.; Ting, J.P-Y. The NLRP3 inflammasome: molecular activation and regulation to therapeutics. Nat. Rev. Immunol., 2019, 19(8), 477-489.
[http://dx.doi.org/10.1038/s41577-019-0165-0] [PMID: 31036962]
[2]
Yang, Y.; Wang, H.; Kouadir, M.; Song, H.; Shi, F. Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors. Cell Death Dis., 2019, 10(2), 128.
[http://dx.doi.org/10.1038/s41419-019-1413-8] [PMID: 30755589]
[3]
Correa, R.G.; Milutinovic, S.; Reed, J.C. Roles of NOD1 (NLRC1) and NOD2 (NLRC2) in innate immunity and inflammatory diseases. Biosci. Rep., 2012, 32(6), 597-608.
[http://dx.doi.org/10.1042/BSR20120055] [PMID: 22908883]
[4]
Schroder, K.; Tschopp, J. The inflammasomes. Cell, 2010, 140(6), 821-832.
[http://dx.doi.org/10.1016/j.cell.2010.01.040] [PMID: 20303873]
[5]
Tukhvatulin, A.I.; Gitlin, I.I.; Shcheblyakov, D.V.; Artemicheva, N.M.; Burdelya, L.G.; Shmarov, M.M.; Naroditsky, B.S.; Gudkov, A.V.; Gintsburg, A.L.; Logunov, D.Y. Combined stimulation of Toll-like receptor 5 and NOD1 strongly potentiates activity of NF-κB, resulting in enhanced innate immune reactions and resistance to Salmonella enterica serovar Typhimurium infection. Infect. Immun., 2013, 81(10), 3855-3864.
[http://dx.doi.org/10.1128/IAI.00525-13] [PMID: 23897616]
[6]
Furman, D.; Campisi, J.; Verdin, E.; Carrera-Bastos, P.; Targ, S.; Franceschi, C.; Ferrucci, L.; Gilroy, D.W.; Fasano, A.; Miller, G.W.; Miller, A.H.; Mantovani, A.; Weyand, C.M.; Barzilai, N.; Goronzy, J.J.; Rando, T.A.; Effros, R.B.; Lucia, A.; Kleinstreuer, N.; Slavich, G.M. Chronic inflammation in the etiology of disease across the life span. Nat. Med., 2019, 25(12), 1822-1832.
[http://dx.doi.org/10.1038/s41591-019-0675-0] [PMID: 31806905]
[7]
Medzhitov, R. Origin and physiological roles of inflammation. Nature, 2008, 454(7203), 428-435.
[http://dx.doi.org/10.1038/nature07201] [PMID: 18650913]
[8]
Straub, R.H. Evolutionary medicine and chronic inflammatory state--known and new concepts in pathophysiology. J. Mol. Med. (Berl.), 2012, 90(5), 523-534.
[http://dx.doi.org/10.1007/s00109-012-0861-8] [PMID: 22271169]
[9]
Wang, A; Huen, SC; Luan, HH; Yu, S; Zhang, C; Gallezot, J-D Opposing effects of fasting metabolism on tissue tolerance in bacterial and viral inflammation Cell, 2016, 166(6), 1512-25.
[http://dx.doi.org/10.1016/j.cell.2016.07.026]
[10]
Ehlers, S.; Kaufmann, S.H. Participants of the 99(th) Dahlem Conference. Infection, inflammation, and chronic diseases: consequences of a modern lifestyle. Trends Immunol., 2010, 31(5), 184-190.
[http://dx.doi.org/10.1016/j.it.2010.02.003] [PMID: 20399709]
[11]
Goto, M. Inflammaging (inflammation + aging): A driving force for human aging based on an evolutionarily antagonistic pleiotropy theory? Biosci. Trends, 2008, 2(6), 218-230.
[PMID: 20103932]
[12]
Straub, R.H.; Schradin, C. Chronic inflammatory systemic diseases: An evolutionary trade-off between acutely beneficial but chronically harmful programs. Evol. Med. Public Health, 2016, 2016(1), 37-51.
[http://dx.doi.org/10.1093/emph/eow001] [PMID: 26817483]
[13]
Chen, G.Y.; Nuñez, G. Sterile inflammation: Sensing and reacting to damage. Nat. Rev. Immunol., 2010, 10(12), 826-837.
[http://dx.doi.org/10.1038/nri2873] [PMID: 21088683]
[14]
Shen, H.; Kreisel, D.; Goldstein, D.R. Processes of sterile inflammation. J. Immunol., 2013, 191(6), 2857-2863.
[http://dx.doi.org/10.4049/jimmunol.1301539] [PMID: 24014880]
[15]
Guo, W.; Sun, Y.; Liu, W.; Wu, X.; Guo, L.; Cai, P.; Wu, X.; Wu, X.; Shen, Y.; Shu, Y.; Gu, Y.; Xu, Q. Small molecule-driven mitophagy-mediated NLRP3 inflammasome inhibition is responsible for the prevention of colitis-associated cancer. Autophagy, 2014, 10(6), 972-985.
[http://dx.doi.org/10.4161/auto.28374] [PMID: 24879148]
[16]
Martinon, F.; Burns, K.; Tschopp, J. The inflammasome: A molecular platform triggering activation of inflammatory caspases and processing of proIL-β. Mol. Cell, 2002, 10(2), 417-426.
[http://dx.doi.org/10.1016/S1097-2765(02)00599-3] [PMID: 12191486]
[17]
Fink, S.L.; Cookson, B.T. Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells. Infect. Immun., 2005, 73(4), 1907-1916.
[http://dx.doi.org/10.1128/IAI.73.4.1907-1916.2005] [PMID: 15784530]
[18]
Di Virgilio, F. The therapeutic potential of modifying inflammasomes and NOD-like receptors. Pharmacol. Rev., 2013, 65(3), 872-905.
[http://dx.doi.org/10.1124/pr.112.006171] [PMID: 23592611]
[19]
Bauernfeind, F.G.; Horvath, G.; Stutz, A.; Alnemri, E.S.; MacDonald, K.; Speert, D.; Fernandes-Alnemri, T.; Wu, J.; Monks, B.G.; Fitzgerald, K.A.; Hornung, V.; Latz, E. Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. J. Immunol., 2009, 183(2), 787-791.
[http://dx.doi.org/10.4049/jimmunol.0901363] [PMID: 19570822]
[20]
Ozaki, E.; Campbell, M.; Doyle, S.L. Targeting the NLRP3 inflammasome in chronic inflammatory diseases: current perspectives. J. Inflamm. Res., 2015, 8, 15-27.
[PMID: 25653548]
[21]
Harijith, A.; Ebenezer, D.L.; Natarajan, V. Reactive oxygen species at the crossroads of inflammasome and inflammation. Front. Physiol., 2014, 5, 352.
[http://dx.doi.org/10.3389/fphys.2014.00352] [PMID: 25324778]
[22]
Benetti, E; Chiazza, F; Patel, NS; Collino, M The NLRP3 Inflammasome as a novel player of the intercellular crosstalk in metabolic disorders. Mediators Inflamm, 2013, 678627.
[http://dx.doi.org/10.1155/2013/678627]
[23]
Patel, M.N.; Carroll, R.G.; Galván-Peña, S.; Mills, E.L.; Olden, R.; Triantafilou, M.; Wolf, A.I.; Bryant, C.E.; Triantafilou, K.; Masters, S.L. Inflammasome Priming in Sterile Inflammatory Disease. Trends Mol. Med., 2017, 23(2), 165-180.
[http://dx.doi.org/10.1016/j.molmed.2016.12.007] [PMID: 28109721]
[24]
Cassel, S.L.; Sutterwala, F.S. Sterile inflammatory responses mediated by the NLRP3 inflammasome. Eur. J. Immunol., 2010, 40(3), 607-611.
[http://dx.doi.org/10.1002/eji.200940207] [PMID: 20201012]
[25]
Bezbradica, J.S.; Coll, R.C.; Schroder, K. Sterile signals generate weaker and delayed macrophage NLRP3 inflammasome responses relative to microbial signals. Cell. Mol. Immunol., 2017, 14(1), 118-126.
[http://dx.doi.org/10.1038/cmi.2016.11] [PMID: 26996064]
[26]
Ko, J.H.; Yoon, S-O.; Lee, H.J.; Oh, J.Y. Rapamycin regulates macrophage activation by inhibiting NLRP3 inflammasome-p38 MAPK-NFκB pathways in autophagy- and p62-dependent manners. Oncotarget, 2017, 8(25), 40817-40831.
[http://dx.doi.org/10.18632/oncotarget.17256] [PMID: 28489580]
[27]
Kawasaki, N.; Asada, R.; Saito, A.; Kanemoto, S.; Imaizumi, K. Obesity-induced endoplasmic reticulum stress causes chronic inflammation in adipose tissue. Sci. Rep., 2012, 2, 799.
[http://dx.doi.org/10.1038/srep00799] [PMID: 23150771]
[28]
Tripathi, Y.B.; Pandey, V. Obesity and endoplasmic reticulum (ER) stresses. Front. Immunol., 2012, 3, 240.
[http://dx.doi.org/10.3389/fimmu.2012.00240] [PMID: 22891067]
[29]
Hotamisligil, G.S. Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell, 2010, 140(6), 900-917.
[http://dx.doi.org/10.1016/j.cell.2010.02.034] [PMID: 20303879]
[30]
Lebeaupin, C.; Proics, E.; de Bieville, C.H.; Rousseau, D.; Bonnafous, S.; Patouraux, S.; Adam, G.; Lavallard, V.J.; Rovere, C.; Le Thuc, O.; Saint-Paul, M.C.; Anty, R.; Schneck, A.S.; Iannelli, A.; Gugenheim, J.; Tran, A.; Gual, P.; Bailly-Maitre, B. ER stress induces NLRP3 inflammasome activation and hepatocyte death. Cell Death Dis., 2015, 6(9), e1879.
[http://dx.doi.org/10.1038/cddis.2015.248] [PMID: 26355342]
[31]
McGettrick, A.F.; O’Neill, L.A. How metabolism generates signals during innate immunity and inflammation. J. Biol. Chem., 2013, 288(32), 22893-22898.
[http://dx.doi.org/10.1074/jbc.R113.486464] [PMID: 23798679]
[32]
Wen, H.; Ting, J.P.; O’Neill, L.A. A role for the NLRP3 inflammasome in metabolic diseases--did Warburg miss inflammation? Nat. Immunol., 2012, 13(4), 352-357.
[http://dx.doi.org/10.1038/ni.2228] [PMID: 22430788]
[33]
Goldberg, E.; Youm, Y-H.; Nguyen, K.; Alnemri, E.; Dixit, V. Ketone body beta-hydroxy butyrate deactivates NLRP3 inflammasome in myeloid cells (CAM1P. 153); Am Assoc Immnol, 2015.
[34]
Goldberg, E.L.; Asher, J.L.; Molony, R.D.; Shaw, A.C.; Zeiss, C.J.; Wang, C.; Morozova-Roche, L.A.; Herzog, R.I.; Iwasaki, A.; Dixit, V.D. β-Hydroxybutyrate deactivates neutrophil NLRP3 Inflammasome to relieve gout flares. Cell Rep., 2017, 18(9), 2077-2087.
[http://dx.doi.org/10.1016/j.celrep.2017.02.004] [PMID: 28249154]
[35]
Yuk, J-M.; Jo, E-K. Crosstalk between autophagy and inflammasomes. Mol. Cells, 2013, 36(5), 393-399.
[http://dx.doi.org/10.1007/s10059-013-0298-0] [PMID: 24213677]
[36]
Wen, H.; Gris, D.; Lei, Y.; Jha, S.; Zhang, L.; Huang, M.T-H.; Brickey, W.J.; Ting, J.P. Fatty acid-induced NLRP3-ASC inflammasome activation interferes with insulin signaling. Nat. Immunol., 2011, 12(5), 408-415.
[http://dx.doi.org/10.1038/ni.2022] [PMID: 21478880]
[37]
Salminen, A.; Kaarniranta, K.; Kauppinen, A. Inflammaging: disturbed interplay between autophagy and inflammasomes. Aging (Albany NY), 2012, 4(3), 166-175.
[http://dx.doi.org/10.18632/aging.100444] [PMID: 22411934]
[38]
Jung, U.J.; Choi, M-S. Obesity and its metabolic complications: the role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease. Int. J. Mol. Sci., 2014, 15(4), 6184-6223.
[http://dx.doi.org/10.3390/ijms15046184] [PMID: 24733068]
[39]
Lee, H-M.; Kim, J-J.; Kim, H.J.; Shong, M.; Ku, B.J.; Jo, E-K. Upregulated NLRP3 inflammasome activation in patients with type 2 diabetes. Diabetes, 2013, 62(1), 194-204.
[http://dx.doi.org/10.2337/db12-0420] [PMID: 23086037]
[40]
Vandanmagsar, B.; Youm, Y-H.; Ravussin, A.; Galgani, J.E.; Stadler, K.; Mynatt, R.L.; Ravussin, E.; Stephens, J.M.; Dixit, V.D. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat. Med., 2011, 17(2), 179-188.
[http://dx.doi.org/10.1038/nm.2279] [PMID: 21217695]
[41]
Horng, T.; Hotamisligil, G.S. Linking the inflammasome to obesity-related disease. Nat. Med., 2011, 17(2), 164-165.
[http://dx.doi.org/10.1038/nm0211-164] [PMID: 21297609]
[42]
Masters, SL; Latz, E; O’Neill, LA The inflammasome in atherosclerosis and type 2 diabetes Sci Transl Med, 2011, 3(81)
[http://dx.doi.org/10.1126/scitranslmed.3001902]
[43]
Kahn, B.B.; Alquier, T.; Carling, D.; Hardie, D.G. AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab., 2005, 1(1), 15-25.
[http://dx.doi.org/10.1016/j.cmet.2004.12.003] [PMID: 16054041]
[44]
Hardie, D.G. AMP-activated protein kinase: an energy sensor that regulates all aspects of cell function. Genes Dev., 2011, 25(18), 1895-1908.
[http://dx.doi.org/10.1101/gad.17420111] [PMID: 21937710]
[45]
Zhang, C-S.; Hawley, S.A.; Zong, Y.; Li, M.; Wang, Z.; Gray, A.; Ma, T.; Cui, J.; Feng, J.W.; Zhu, M.; Wu, Y.Q.; Li, T.Y.; Ye, Z.; Lin, S.Y.; Yin, H.; Piao, H.L.; Hardie, D.G.; Lin, S.C. Fructose-1,6-bisphosphate and aldolase mediate glucose sensing by AMPK. Nature, 2017, 548(7665), 112-116.
[http://dx.doi.org/10.1038/nature23275] [PMID: 28723898]
[46]
Gejjalagere Honnappa, C.; Mazhuvancherry Kesavan, U. A concise review on advances in development of small molecule anti-inflammatory therapeutics emphasising AMPK: An emerging target. Int. J. Immunopathol. Pharmacol., 2016, 29(4), 562-571.
[http://dx.doi.org/10.1177/0394632016673369] [PMID: 27707958]
[47]
Mor, V.; Unnikrishnan, M.K. 5′-adenosine monophosphate-activated protein kinase and the metabolic syndrome. Endocr. Metab. Immune Disord. Drug Targets, 2011, 11(3), 206-216.
[http://dx.doi.org/10.2174/187153011796429844] [PMID: 21831034]
[48]
Mathew, G.; Thambi, M.; Unnikrishnan, M.K. A multimodal Darwinian strategy for alleviating the atherosclerosis pandemic. Med. Hypotheses, 2014, 82(2), 159-162.
[http://dx.doi.org/10.1016/j.mehy.2013.11.025] [PMID: 24355423]
[49]
Mathew, G.; Unnikrishnan, M.K. Multi-target drugs to address multiple checkpoints in complex inflammatory pathologies: evolutionary cues for novel “first-in-class” anti-inflammatory drug candidates: a reviewer’s perspective. Inflamm. Res., 2015, 64(10), 747-752.
[http://dx.doi.org/10.1007/s00011-015-0851-8] [PMID: 26186905]
[50]
Mathew, G.; Sharma, A.; Pickering, R.J.; Rosado, C.J.; Lemarie, J.; Mudgal, J.; Thambi, M.; Sebastian, S.; Jandeleit-Dahm, K.A.; de Haan, J.B.; Unnikrishnan, M.K. A novel synthetic small molecule DMFO targets Nrf2 in modulating proinflammatory/antioxidant mediators to ameliorate inflammation. Free Radic. Res., 2018, 52(10), 1140-1157.
[http://dx.doi.org/10.1080/10715762.2018.1533636] [PMID: 30422019]
[51]
Salminen, A.; Hyttinen, J.M.; Kaarniranta, K. AMP-activated protein kinase inhibits NF-κB signaling and inflammation: impact on healthspan and lifespan. J. Mol. Med. (Berl.), 2011, 89(7), 667-676.
[http://dx.doi.org/10.1007/s00109-011-0748-0] [PMID: 21431325]
[52]
Sag, D.; Carling, D.; Stout, R.D.; Suttles, J. Adenosine 5′-monophosphate-activated protein kinase promotes macrophage polarization to an anti-inflammatory functional phenotype. J. Immunol., 2008, 181(12), 8633-8641.
[http://dx.doi.org/10.4049/jimmunol.181.12.8633] [PMID: 19050283]
[53]
O’Neill, L.A.; Hardie, D.G. Metabolism of inflammation limited by AMPK and pseudo-starvation. Nature, 2013, 493(7432), 346-355.
[http://dx.doi.org/10.1038/nature11862] [PMID: 23325217]
[54]
Muñoz-Planillo, R.; Kuffa, P.; Martínez-Colón, G.; Smith, B.L.; Rajendiran, T.M.; Núñez, G. K+ efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter. Immunity, 2013, 38(6), 1142-1153.
[http://dx.doi.org/10.1016/j.immuni.2013.05.016] [PMID: 23809161]
[55]
Zheng, D.; Perianayagam, A.; Lee, D.H.; Brannan, M.D.; Yang, L.E.; Tellalian, D.; Chen, P.; Lemieux, K.; Marette, A.; Youn, J.H.; McDonough, A.A. AMPK activation with AICAR provokes an acute fall in plasma [K+ Am. J. Physiol. Cell Physiol., 2008, 294(1), C126-C135. [K+
[http://dx.doi.org/10.1152/ajpcell.00464.2007] [PMID: 18003746]
[56]
Russell, R.C.; Yuan, H-X.; Guan, K-L. Autophagy regulation by nutrient signaling. Cell Res., 2013.
[PMID: 24343578]
[57]
Bullón, P.; Alcocer-Gómez, E.; Carrión, A.M.; Marín-Aguilar, F.; Garrido-Maraver, J.; Román-Malo, L.; Ruiz-Cabello, J.; Culic, O.; Ryffel, B.; Apetoh, L.; Ghiringhelli, F.; Battino, M.; Sánchez-Alcazar, J.A.; Cordero, M.D. AMPK phosphorylation modulates pain by activation of NLRP3 inflammasome. Antioxid. Redox Signal., 2016, 24(3), 157-170.
[http://dx.doi.org/10.1089/ars.2014.6120] [PMID: 26132721]
[58]
Traba, J.; Kwarteng-Siaw, M.; Okoli, T.C.; Li, J.; Huffstutler, R.D.; Bray, A.; Waclawiw, M.A.; Han, K.; Pelletier, M.; Sauve, A.A.; Siegel, R.M.; Sack, M.N. Fasting and refeeding differentially regulate NLRP3 inflammasome activation in human subjects. J. Clin. Invest., 2015, 125(12), 4592-4600.
[http://dx.doi.org/10.1172/JCI83260] [PMID: 26529255]
[59]
Liu, X.; Zhang, X.; Ding, Y.; Zhou, W.; Tao, L.; Lu, P.; Wang, Y.; Hu, R. Nuclear factor E2-related factor-2 negatively regulates NLRP3 inflammasome activity by inhibiting reactive oxygen species-induced NLRP3 priming. Antioxid. Redox Signal., 2017, 26(1), 28-43.
[http://dx.doi.org/10.1089/ars.2015.6615] [PMID: 27308893]
[60]
Salminen, A.; Kaarniranta, K. AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network. Ageing Res. Rev., 2012, 11(2), 230-241.
[http://dx.doi.org/10.1016/j.arr.2011.12.005] [PMID: 22186033]
[61]
Li, A.; Zhang, S.; Li, J.; Liu, K.; Huang, F.; Liu, B. Metformin and resveratrol inhibit Drp1-mediated mitochondrial fission and prevent ER stress-associated NLRP3 inflammasome activation in the adipose tissue of diabetic mice. Mol. Cell. Endocrinol., 2016, 434, 36-47.
[http://dx.doi.org/10.1016/j.mce.2016.06.008] [PMID: 27276511]
[62]
Dandapani, M.; Hardie, D.G. AMPK: opposing the metabolic changes in both tumour cells and inflammatory cells? Biochem. Soc. Trans., 2013, 41(2), 687-693.
[http://dx.doi.org/10.1042/BST20120351] [PMID: 23514177]
[63]
Harada, K.; Ferdous, T.; Harada, T.; Ueyama, Y. Metformin in combination with 5-fluorouracil suppresses tumor growth by inhibiting the Warburg effect in human oral squamous cell carcinoma. Int. J. Oncol., 2016, 49(1), 276-284.
[http://dx.doi.org/10.3892/ijo.2016.3523] [PMID: 27210058]
[64]
Lim, C.T.; Kola, B.; Korbonits, M. AMPK as a mediator of hormonal signalling. J. Mol. Endocrinol., 2010, 44(2), 87-97.
[http://dx.doi.org/10.1677/JME-09-0063] [PMID: 19625456]
[65]
Hardie, D.G. AMPK: a target for drugs and natural products with effects on both diabetes and cancer. Diabetes, 2013, 62(7), 2164-2172.
[http://dx.doi.org/10.2337/db13-0368] [PMID: 23801715]
[66]
Prabhakar, P.K.; Doble, M. Mechanism of action of natural products used in the treatment of diabetes mellitus. Chin. J. Integr. Med., 2011, 17(8), 563-574.
[http://dx.doi.org/10.1007/s11655-011-0810-3] [PMID: 21826590]
[67]
Shrungeswara, A.H.; Unnikrishnan, M.K. Evolution of dietary preferences and the innate urge to heal: Drug discovery lessons from Ayurveda. J. Ayurveda Integr. Med., 2019, 10(3), 222-226.
[http://dx.doi.org/10.1016/j.jaim.2017.08.003] [PMID: 29576440]
[68]
Din, FV; Valanciute, A; Houde, VP; Zibrova, D; Green, KA; Sakamoto, K Aspirin inhibits mTOR signaling, activates AMP-activated protein kinase, and induces autophagy in colorectal cancer cells Gastroenterology, 2012, 142(7), 1504-15.
[69]
Sung, J.Y.; Choi, H.C. Aspirin-induced AMP-activated protein kinase activation regulates the proliferation of vascular smooth muscle cells from spontaneously hypertensive rats. Biochem. Biophys. Res. Commun., 2011, 408(2), 312-317.
[http://dx.doi.org/10.1016/j.bbrc.2011.04.027] [PMID: 21514281]
[70]
Kandadi, M.R.; Rajanna, P.K.; Unnikrishnan, M.K.; Boddu, S.P.; Hua, Y.; Li, J.; Du, M.; Ren, J.; Sreejayan, N. 2-(3,4-Dihydro-2H-pyrrolium-1-yl)-3oxoindan-1-olate (DHPO), a novel, synthetic small molecule that alleviates insulin resistance and lipid abnormalities. Biochem. Pharmacol., 2010, 79(4), 623-631.
[http://dx.doi.org/10.1016/j.bcp.2009.09.018] [PMID: 19769946]
[71]
Ren, J.; Fan, C.; Chen, N.; Huang, J.; Yang, Q. Resveratrol pretreatment attenuates cerebral ischemic injury by upregulating expression of transcription factor Nrf2 and HO-1 in rats. Neurochem. Res., 2011, 36(12), 2352-2362.
[http://dx.doi.org/10.1007/s11064-011-0561-8] [PMID: 21850487]
[72]
Gong, Z.; Zhou, J.; Li, H.; Gao, Y.; Xu, C.; Zhao, S.; Chen, Y.; Cai, W.; Wu, J. Curcumin suppresses NLRP3 inflammasome activation and protects against LPS-induced septic shock. Mol. Nutr. Food Res., 2015, 59(11), 2132-2142.
[http://dx.doi.org/10.1002/mnfr.201500316] [PMID: 26250869]
[73]
Wang, C.; Pan, Y.; Zhang, Q-Y.; Wang, F-M.; Kong, L-D. Quercetin and allopurinol ameliorate kidney injury in STZ-treated rats with regulation of renal NLRP3 inflammasome activation and lipid accumulation. PLoS One, 2012, 7(6), e38285.
[http://dx.doi.org/10.1371/journal.pone.0038285] [PMID: 22701621]
[74]
Shao, B-Z.; Xu, Z-Q.; Han, B-Z.; Su, D-F.; Liu, C. NLRP3 inflammasome and its inhibitors: A review. Front. Pharmacol., 2015, 6, 262.
[http://dx.doi.org/10.3389/fphar.2015.00262] [PMID: 26594174]
[75]
Kim, J.K.; Jin, H.S.; Suh, H.W.; Jo, E.K. Negative regulators and their mechanisms in NLRP3 inflammasome activation and signaling. Immunol. Cell Biol., 2017, 95(7), 584-592.
[http://dx.doi.org/10.1038/icb.2017.23] [PMID: 28356568]
[76]
Tőzsér, J; Benkő, S Natural compounds as regulators of NLRP3 inflammasome-mediated IL-1β production Mediators Inflamm, 2016, 2016, 5460302.
[77]
Coll, R.C.; Robertson, A.A.; Chae, J.J.; Higgins, S.C.; Muñoz-Planillo, R.; Inserra, M.C.; Vetter, I.; Dungan, L.S.; Monks, B.G.; Stutz, A.; Croker, D.E.; Butler, M.S.; Haneklaus, M.; Sutton, C.E.; Núñez, G.; Latz, E.; Kastner, D.L.; Mills, K.H.; Masters, S.L.; Schroder, K.; Cooper, M.A.; O’Neill, L.A. A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases. Nat. Med., 2015, 21(3), 248-255.
[http://dx.doi.org/10.1038/nm.3806] [PMID: 25686105]
[78]
He, Y.; Varadarajan, S.; Muñoz-Planillo, R.; Burberry, A.; Nakamura, Y.; Núñez, G. 3,4-methylenedioxy-β-nitrostyrene inhibits NLRP3 inflammasome activation by blocking assembly of the inflammasome. J. Biol. Chem., 2014, 289(2), 1142-1150.
[http://dx.doi.org/10.1074/jbc.M113.515080] [PMID: 24265316]
[79]
Lamkanfi, M.; Mueller, J.L.; Vitari, A.C.; Misaghi, S.; Fedorova, A.; Deshayes, K.; Lee, W.P.; Hoffman, H.M.; Dixit, V.M. Glyburide inhibits the Cryopyrin/Nalp3 inflammasome. J. Cell Biol., 2009, 187(1), 61-70.
[http://dx.doi.org/10.1083/jcb.200903124] [PMID: 19805629]
[80]
Verway, M.; Bouttier, M.; Wang, T-T.; Carrier, M.; Calderon, M.; An, B-S.; Devemy, E.; McIntosh, F.; Divangahi, M.; Behr, M.A.; White, J.H. Vitamin D induces interleukin-1β expression: paracrine macrophage epithelial signaling controls M. tuberculosis infection. PLoS Pathog., 2013, 9(6), e1003407.
[http://dx.doi.org/10.1371/journal.ppat.1003407] [PMID: 23762029]
[81]
Zhao, Y.; Li, Q.; Zhao, W.; Li, J.; Sun, Y.; Liu, K.; Liu, B.; Zhang, N. Astragaloside IV and cycloastragenol are equally effective in inhibition of endoplasmic reticulum stress-associated TXNIP/NLRP3 inflammasome activation in the endothelium. J. Ethnopharmacol., 2015, 169, 210-218.
[http://dx.doi.org/10.1016/j.jep.2015.04.030] [PMID: 25922268]
[82]
Li, Y.; Yang, J.; Chen, M-H.; Wang, Q.; Qin, M-J.; Zhang, T.; Chen, X.Q.; Liu, B.L.; Wen, X.D. Ilexgenin A inhibits endoplasmic reticulum stress and ameliorates endothelial dysfunction via suppression of TXNIP/NLRP3 inflammasome activation in an AMPK dependent manner. Pharmacol. Res., 2015, 99, 101-115.
[http://dx.doi.org/10.1016/j.phrs.2015.05.012] [PMID: 26054569]
[83]
Wu, J.; Xu, X.; Li, Y.; Kou, J.; Huang, F.; Liu, B.; Liu, K. Quercetin, luteolin and epigallocatechin gallate alleviate TXNIP and NLRP3-mediated inflammation and apoptosis with regulation of AMPK in endothelial cells. Eur. J. Pharmacol., 2014, 745, 59-68.
[http://dx.doi.org/10.1016/j.ejphar.2014.09.046] [PMID: 25446924]
[84]
Li, Y.; Li, J.; Li, S.; Li, Y.; Wang, X.; Liu, B.; Fu, Q.; Ma, S. Curcumin attenuates glutamate neurotoxicity in the hippocampus by suppression of ER stress-associated TXNIP/NLRP3 inflammasome activation in a manner dependent on AMPK. Toxicol. Appl. Pharmacol., 2015, 286(1), 53-63.
[http://dx.doi.org/10.1016/j.taap.2015.03.010] [PMID: 25791922]
[85]
Song, J.; Li, J.; Hou, F.; Wang, X.; Liu, B. Mangiferin inhibits endoplasmic reticulum stress-associated thioredoxin-interacting protein/NLRP3 inflammasome activation with regulation of AMPK in endothelial cells. Metabolism, 2015, 64(3), 428-437.
[http://dx.doi.org/10.1016/j.metabol.2014.11.008] [PMID: 25499441]
[86]
Wang, X.; Li, R.; Wang, X.; Fu, Q.; Ma, S. Umbelliferone ameliorates cerebral ischemia-reperfusion injury via upregulating the PPAR gamma expression and suppressing TXNIP/NLRP3 inflammasome. Neurosci. Lett., 2015, 600, 182-187.
[http://dx.doi.org/10.1016/j.neulet.2015.06.016] [PMID: 26071904]
[87]
Hua, K-F.; Yang, S-M.; Kao, T-Y.; Chang, J-M.; Chen, H-L.; Tsai, Y-J.; Chen, A.; Yang, S.S.; Chao, L.K.; Ka, S.M. Osthole mitigates progressive IgA nephropathy by inhibiting reactive oxygen species generation and NF-κB/NLRP3 pathway. PLoS One, 2013, 8(10), e77794.
[http://dx.doi.org/10.1371/journal.pone.0077794] [PMID: 24204969]
[88]
Tsai, P-Y.; Ka, S-M.; Chang, J-M.; Chen, H-C.; Shui, H-A.; Li, C-Y.; Hua, K.F.; Chang, W.L.; Huang, J.J.; Yang, S.S.; Chen, A. Epigallocatechin-3-gallate prevents lupus nephritis development in mice via enhancing the Nrf2 antioxidant pathway and inhibiting NLRP3 inflammasome activation. Free Radic. Biol. Med., 2011, 51(3), 744-754.
[http://dx.doi.org/10.1016/j.freeradbiomed.2011.05.016] [PMID: 21641991]
[89]
Zhang, L.; Wang, X.Z.; Li, Y.S.; Zhang, L.; Hao, L.R. Icariin ameliorates IgA nephropathy by inhibition of nuclear factor kappa b/Nlrp3 pathway. FEBS Open Bio, 2016, 7(1), 54-63.
[http://dx.doi.org/10.1002/2211-5463.12161] [PMID: 28097088]
[90]
Pan, C.W.; Pan, Z.Z.; Hu, J.J.; Chen, W.L.; Zhou, G.Y.; Lin, W.; Jin, L.X.; Xu, C.L. Mangiferin alleviates lipopolysaccharide and D-galactosamine-induced acute liver injury by activating the Nrf2 pathway and inhibiting NLRP3 inflammasome activation. Eur. J. Pharmacol., 2016, 770, 85-91.
[http://dx.doi.org/10.1016/j.ejphar.2015.12.006] [PMID: 26668000]
[91]
Dinesh, P.; Rasool, M. Berberine, an isoquinoline alkaloid suppresses TXNIP mediated NLRP3 inflammasome activation in MSU crystal stimulated RAW 264.7 macrophages through the upregulation of Nrf2 transcription factor and alleviates MSU crystal induced inflammation in rats. Int. Immunopharmacol., 2017, 44, 26-37.
[http://dx.doi.org/10.1016/j.intimp.2016.12.031] [PMID: 28068647]
[92]
Shahzad, K.; Bock, F.; Al-Dabet, M.M.; Gadi, I.; Nazir, S.; Wang, H.; Kohli, S.; Ranjan, S.; Mertens, P.R.; Nawroth, P.P.; Isermann, B. Stabilization of endogenous Nrf2 by minocycline protects against Nlrp3-inflammasome induced diabetic nephropathy. Sci. Rep., 2016, 6, 34228.
[http://dx.doi.org/10.1038/srep34228] [PMID: 27721446]
[93]
Buckner, T; Fan, R; Kim, Y; Kim, J; Chung, S. Annatto Tocotrienol Attenuates NLRP3 inflammasome Activation in Macrophages Curr. Dev. Nutr., 2017, 1(6), e000760.
[http://dx.doi.org/10.3945/cdn.117.000760]
[94]
Ka, S.M.; Kuoping Chao, L.; Lin, J.C.; Chen, S.T.; Li, W.T.; Lin, C.N.; Cheng, J.C.; Jheng, H.L.; Chen, A.; Hua, K.F. A low toxicity synthetic cinnamaldehyde derivative ameliorates renal inflammation in mice by inhibiting NLRP3 inflammasome and its related signaling pathways. Free Radic. Biol. Med., 2016, 91, 10-24.
[http://dx.doi.org/10.1016/j.freeradbiomed.2015.12.003] [PMID: 26675345]
[95]
Zhang, X.; Wang, G.; Gurley, E.C.; Zhou, H. Flavonoid apigenin inhibits lipopolysaccharide-induced inflammatory response through multiple mechanisms in macrophages. PLoS One, 2014, 9(9), e107072.
[http://dx.doi.org/10.1371/journal.pone.0107072] [PMID: 25192391]
[96]
Aruna, R.; Geetha, A.; Suguna, P. Rutin modulates ASC expression in NLRP3 inflammasome: a study in alcohol and cerulein-induced rat model of pancreatitis. Mol. Cell. Biochem., 2014, 396(1-2), 269-280.
[http://dx.doi.org/10.1007/s11010-014-2162-8] [PMID: 25060908]
[97]
Ho, C-L.; Lin, C-Y.; Ka, S-M.; Chen, A.; Tasi, Y-L.; Liu, M-L.; Chiu, Y.C.; Hua, K.F. Bamboo vinegar decreases inflammatory mediator expression and NLRP3 inflammasome activation by inhibiting reactive oxygen species generation and protein kinase C-α/δ activation. PLoS One, 2013, 8(10), e75738.
[http://dx.doi.org/10.1371/journal.pone.0075738] [PMID: 24124509]
[98]
Qiu, J.; Wang, M.; Zhang, J.; Cai, Q.; Lu, D.; Li, Y.; Dong, Y.; Zhao, T.; Chen, H. The neuroprotection of Sinomenine against ischemic stroke in mice by suppressing NLRP3 inflammasome via AMPK signaling. Int. Immunopharmacol., 2016, 40, 492-500.
[http://dx.doi.org/10.1016/j.intimp.2016.09.024] [PMID: 27769021]
[99]
Chen, L.; Lan, Z. Polydatin attenuates potassium oxonate-induced hyperuricemia and kidney inflammation by inhibiting NF-κB/NLRP3 inflammasome activation via the AMPK/SIRT1 pathway. Food Funct., 2017, 8(5), 1785-1792.
[http://dx.doi.org/10.1039/C6FO01561A] [PMID: 28428988]
[100]
Wu, J.; Li, X.; Zhu, G.; Zhang, Y.; He, M.; Zhang, J. The role of Resveratrol-induced mitophagy/autophagy in peritoneal mesothelial cells inflammatory injury via NLRP3 inflammasome activation triggered by mitochondrial ROS. Exp. Cell Res., 2016, 341(1), 42-53.
[http://dx.doi.org/10.1016/j.yexcr.2016.01.014] [PMID: 26825654]
[101]
Kim, Y.; Wang, W.; Okla, M.; Kang, I.; Moreau, R.; Chung, S. Suppression of NLRP3 inflammasome by γ-tocotrienol ameliorates type 2 diabetes. J. Lipid Res., 2016, 57(1), 66-76.
[http://dx.doi.org/10.1194/jlr.M062828] [PMID: 26628639]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy