Login Register Cart 0
Generic placeholder image

Current Drug Research Reviews

Editor-in-Chief

ISSN (Print): 2589-9775
ISSN (Online): 2589-9783

Back
Journal Home About Journal Editorial Board Current Issue Volumes/Issues
Subscribe
Review Article

Therapeutic Potential of Diacerein in Management of Pain

Author(s): Vishal Patel, Amit Joharapurkar* and Mukul Jain

Volume 14, Issue 3, 2022

Published on: 04 August, 2022

Page: [215 - 224] Pages: 10

DOI: 10.2174/2589977514666220428124623

Price: $65

Abstract

Diacerein (DCN), an analogue of rhein (a glycosidal compound of natural origin), is currently used in the treatment of osteoarthritis and is given a fast-track designation for development to treat epidermolysis bullosa (EB). It is a nonsteroidal anti-inflammatory drug having disease-modifying properties in osteoarthritis and anti-inflammatory effects for the treatment of EB. Diacerein has a beneficial effect on pain relief and demonstrated antioxidant and anti-apoptotic effects, which are useful in renal disease, diabetes, and other disorders. This review discusses the possible mechanism of diacerein in the management of pain. The potential role of rhein and diacerein in the treatment of neuropathic, inflammatory and nociceptive pain is also reviewed. The effect of diacerein and rhein on mediators of pain, such as transient receptor potential cation channel subfamily V (TRPV1), Substance P, glutamate, inflammatory cytokines, nitric oxide, matrix metalloproteinases, histamine, palmitoylethanolamide, nuclear factor-kappa B (NFkB), and prostaglandin, has also been discussed. The data highlights the role of diacerein in neuropathic, nociceptive and inflammatory pain. Clinical trials and mechanism of action studies are needed to ascertain the role of diacerein, rhein or their analogues in the management of pain, alone or in combination with other approved therapies.

Keywords: Diacerein, rhein, inflammatory, nociceptive, neuropathic, pain.

« Previous Next »
Graphical Abstract

[1]
Anchel, M. Identification of the antibiotic substance from Cassia reticulata as 4,5-dihydroxyanthraquinone-2-carboxylic acid. J. Biol. Chem., 1949, 177(1), 169-177.
[http://dx.doi.org/10.1016/S0021-9258(18)57072-1] [PMID: 18123056]
[2]
Nawa, H.; Uchibayashi, M.; Matsuoka, T. Structure of rhein. J. Org. Chem., 1961, 26(3), 979-981.
[http://dx.doi.org/10.1021/jo01062a628]
[3]
Khattak, A.K.; Hassan, S.M.; Mughal, S.S. General overview of phytochemistry and pharmacological potential of rheum palmatum (Chinese rhubarb). Innovare J Ayurvedic Sci, 2020, 8(6), 5-9.
[http://dx.doi.org/10.22159/ijas.2020.v8i6.39192]
[4]
Fairbairn, J.W. The active constituents of the vegetable purgatives containing anthracene derivatives; glycosides and aglycones. J. Pharm. Pharmacol., 1949, 1(10), 683-694.
[PMID: 18143085]
[5]
Hoerhammer, L.; Wagner, H.; Koehler, I. New investigations on the components of Rheum palmatum L. Part 1: On the analysis of rhein. Arch. Pharm. Ber. Dtsch. Pharm. Ges., 1959, 292(64), 591-601.
[PMID: 14402302]
[6]
Lemli, J.; Dequeker, R.; Cuveele, J. Studies in the field of anthraquinone drugs. II. Presence of rhein-dianthrone in the roots of Rheum palma-tum. Pharm. Weekbl., 1963, 98, 529-533.
[PMID: 13929561]
[7]
Bellaart, A.C. Studies on rhubarb root grown in the Netherlands. III. The structure of the glycosides of rhein. Pharm. Weekbl., 1954, 89(33-34), 579-581.
[PMID: 13194358]
[8]
Kean, E.A. Rhein: An inhibitor of mitochondrial oxidations. Arch. Biochem. Biophys., 1968, 127(1), 528-533.
[http://dx.doi.org/10.1016/0003-9861(68)90258-0] [PMID: 4301566]
[9]
Kean, E.A. Inhibitory action of rhein on the reduced nicotinamide adenine dinucleotidedehydrogenase complex of mitochondrial particles and on other dehydrogenases. Biochem. Pharmacol., 1970, 19(7), 2201-2202.
[http://dx.doi.org/10.1016/0006-2952(70)90119-X] [PMID: 4329037]
[10]
Kean, E.A.; Gutman, M.; Singer, T.P. Rhein, a selective inhibitor of the DPNH-flavin step in mitochondrial electron transport. Biochem. Biophys. Res. Commun., 1970, 40(6), 1507-1513.
[http://dx.doi.org/10.1016/0006-291X(70)90039-2] [PMID: 4104098]
[11]
Ewe, K. Effect of rhein on the transport of electrolytes, water, and carbohydrates in the human jejunum and colon. Pharmacology, 1980, 20(Suppl. 1), 27-35.
[http://dx.doi.org/10.1159/000137395] [PMID: 6246548]
[12]
Goerg, K.J.; Wanitschke, R.; Schulz, L. Scanning electron microscopic study of the effect of rhein on the surface morphology of the rat colon-ic mucosa. Pharmacology, 1980, 20(Suppl. 1), 36-42.
[http://dx.doi.org/10.1159/000137396] [PMID: 7375504]
[13]
Raimondi, L.; Banchelli Soldaini, G.; Buffoni, F. Rhein and derivatives. In vitro studies on their capacity to inhibit certain proteases. Pharmacol. Res. Commun., 1982, 14(2), 103-112.
[http://dx.doi.org/10.1016/S0031-6989(82)80091-X] [PMID: 6803254]
[14]
Cheng, L.; Chen, Q.; Pi, R.; Chen, J. A research update on the therapeutic potential of rhein and its derivatives. Eur. J. Pharmacol., 2021, 899, 173908.
[http://dx.doi.org/10.1016/j.ejphar.2021.173908] [PMID: 33515540]
[15]
Yao, W.; Xu, Z.; Sun, J.; Luo, J.; Wei, Y.; Zou, J. Deoxycholic acid-functionalised nanoparticles for oral delivery of rhein. Eur. J. Pharm. Sci., 2021, 159, 105713.
[http://dx.doi.org/10.1016/j.ejps.2021.105713] [PMID: 33453389]
[16]
Hao, K.; Qi, Q.; Wan, P. Prediction of human pharmacokinetics from preclinical information of rhein, an antidiabetic nephropathy drug, using a physiologically based pharmacokinetic model. Basic Clin. Pharmacol. Toxicol., 2014, 114(2), 160-167.
[http://dx.doi.org/10.1111/bcpt.12148] [PMID: 24118734]
[17]
Diacerein - Neopharmed Gentili - AdisInsight. Available from: https://adisinsight.springer.com Available from: https://adisinsight.springer.com/drugs/800004670 (Accessed on 2021 November 20).
[18]
Nicolas, P.; Tod, M.; Padoin, C.; Petitjean, O. Clinical pharmacokinetics of diacerein. Clin. Pharmacokinet., 1998, 35(5), 347-359.
[http://dx.doi.org/10.2165/00003088-199835050-00002] [PMID: 9839088]
[19]
Notification of a referral under article 31 of directive 2001/83/ECNotification of a referral under article 31 of directive 2001/83/EC 2001.
[20]
Higgs, G.A.; Harvey, E.A.; Ferreira, S.H.; Vane, J.R. The effects of antiinflammatory drugs on the production of prostaglandins in vivo. Adv. Prostaglandin Thromboxane Res., 1976, 1, 105-110.
[PMID: 826136]
[21]
Pomarelli, P.; Berti, M.; Gatti, M.T.; Mosconi, P. A non steroidal anti-inflammatory drug that stimulates prostaglandin release. Farmaco, Sci., 1980, 35(10), 836-842.
[PMID: 7450019]
[22]
Kay, A.G.L.; Griffiths, L.G.; Volans, G.N.; Grahame, R. Preliminary experience with diacetylrhein in the treatment of osteoarthritis. Curr. Med. Res. Opin., 1980, 6(8), 548-551.
[http://dx.doi.org/10.1185/03007998009109485] [PMID: 7389385]
[23]
Carrabba, M.; Mele, G.; Chevallard, M.; Angelini, M. Diacereina: Un approccio “originale” nel trattamento dei reumatismi degenerativi e/o ex-tra-articolari. Minerva Med., 1987, 78(3), 179-185.
[PMID: 3547179]
[24]
Schöngen, R.N.; Giannetti, B.M.; van de Leur, E.; Reinards, R.; Greiling, H. Effect of diacetylrhein on the phagocytosis of polymorphonuclear leucocytes and its influence on the biosynthesis of hyaluronate in synovial cells. Arzneimittelforschung, 1988, 38(5), 744-748.
[PMID: 3415721]
[25]
Mian, M.; Benetti, D.; Rosini, S.; Fantozzi, R. Rhein reduces proteoglycan loss during the autolytic breakdown of cultured cartilage. Int. J. Tissue React., 1989, 11(3), 117-122.
[PMID: 2613456]
[26]
Taccoen, A.; Berdah, L. Diacetylrhein, a new therapeutic approach of osteoarthritis. Rev. Rhum., 1993, 60(6 Pt 2), 83S-86S.
[PMID: 8118457]
[27]
Wally, V.; Kitzmueller, S.; Lagler, F. Topical diacerein for epidermolysis bullosa: A randomized controlled pilot study. Orphanet J. Rare Dis., 2013, 8(1), 69.
[http://dx.doi.org/10.1186/1750-1172-8-69] [PMID: 23651789]
[28]
Medicines Agency E. Public summary of opinion on orphan designation Diacerein for the treatment of epidermolysis bullosa 2019.
[29]
Saha, N.; Moldovan, F.; Tardif, G.; Pelletier, J.P.; Cloutier, J.M.; Martel-Pelletier, J. Interleukin-1beta-converting enzyme/caspase-1 in human oste-oarthritic tissues: Localization and role in the maturation of interleukin-1beta and interleukin-18. Arthritis Rheum., 1999, 42(8), 1577-1587.
[http://dx.doi.org/10.1002/1529-0131(199908)42:8<1577:AID-ANR3>3.0.CO;2-Z] [PMID: 10446854]
[30]
Vincent, T.L. Il-1 in osteoarthritis: Time for a critical review of the literature. F1000 Res., 2019, 8(F1000)
[31]
Richette, P.; François, M.; Vicaut, E. A high interleukin 1 receptor antagonist/IL-1beta ratio occurs naturally in knee osteoarthritis. J. Rheumatol., 2008, 35(8), 1650-1654.
[PMID: 18597398]
[32]
Moldovan, F.; Pelletier, J.P.; Jolicoeur, F.C.; Cloutier, J.M.; Martel-Pelletier, J. Diacerhein and rhein reduce the ICE-induced IL-1β and IL-18 acti-vation in human osteoarthritic cartilage. Osteoarthritis Cartilage, 2000, 8(3), 186-196.
[http://dx.doi.org/10.1053/joca.1999.0289] [PMID: 10806046]
[33]
Martel-Pelletier, J.; Mineau, F.; Jolicoeur, F.C.; Cloutier, J.M.; Pelletier, J.P. In vitro effects of diacerhein and rhein on interleukin 1 and tumor necrosis factor-alpha systems in human osteoarthritic synovium and chondrocytes. J. Rheumatol., 1998, 25(4), 753-762.
[PMID: 9558181]
[34]
Sun, H.; Luo, G.; Chen, D.; Xiang, Z. A comprehensive and system review for the pharmacological mechanism of action of rhein, an active anthraquinone ingredient. Front. Pharmacol., 2016, 7, 247.
[http://dx.doi.org/10.3389/fphar.2016.00247] [PMID: 27582705]
[35]
Steinecker-Frohnwieser, B.; Kaltenegger, H.; Weigl, L. Pharmacological treatment with diacerein combined with mechanical stimulation affects the expression of growth factors in human chondrocytes. Biochem. Biophys. Rep., 2017, 11, 154-160.
[http://dx.doi.org/10.1016/j.bbrep.2017.06.006] [PMID: 28955780]
[36]
Domagala, F.; Martin, G.; Bogdanowicz, P.; Ficheux, H.; Pujol, J.P. Inhibition of interleukin-1β-induced activation of MEK/ERK pathway and DNA binding of NF-kappaB and AP-1: Potential mechanism for Diacerein effects in osteoarthritis. Biorheology, 2006, 43(3,4), 577-587.
[PMID: 16912429]
[37]
Felisaz, N.; Boumediene, K.; Ghayor, C. Stimulating effect of diacerein on TGF-β1 and β2 expression in articular chondrocytes cultured with and without interleukin-1. Osteoarthritis Cartilage, 1999, 7(3), 255-264.
[http://dx.doi.org/10.1053/joca.1998.0199] [PMID: 10329300]
[38]
Legendre, F.; Heuze, A.; Boukerrouche, K. Rhein, the metabolite of diacerhein, reduces the proliferation of osteoarthritic chondrocytes and synoviocytes without inducing apoptosis. Scand. J. Rheumatol., 2009, 38(2), 104-111.
[http://dx.doi.org/10.1080/03009740802421996] [PMID: 19274517]
[39]
Limmer, A.L.; Nwannunu, C.E.; Shah, R. Topical diacerein ointment for epidermolysis bullosa simplex: A review. Skin Therapy Lett., 2019, 24(3), 7-9.
[PMID: 31095348]
[40]
Wally, V.; Lettner, T.; Peking, P. The pathogenetic role of IL-1β in severe epidermolysis bullosa simplex. J. Invest. Dermatol., 2013, 133(7), 1901-1903.
[http://dx.doi.org/10.1038/jid.2013.31] [PMID: 23344459]
[41]
Kaur, D.; Kaur, J.; Kamal, S. Diacerein, its beneficial impact on chondrocytes and notable new clinical applications. J. Pharm. Sci., 2018, 54(4), 17534.
[42]
Garlanda, C.; Dinarello, C.A.; Mantovani, A. The interleukin-1 family: Back to the future. Immunity, 2013, 39(6), 1003-1018.
[http://dx.doi.org/10.1016/j.immuni.2013.11.010] [PMID: 24332029]
[43]
Mantovani, A.; Dinarello, C.A.; Molgora, M.; Garlanda, C. Interleukin-1 and related cytokines in the regulation of inflammation and immunity. Immunity, 2019, 50(4), 778-795.
[http://dx.doi.org/10.1016/j.immuni.2019.03.012] [PMID: 30995499]
[44]
Kim, K.H.; Seo, H.J.; Abdi, S.; Huh, B. All about pain pharmacology: What pain physicians should know. Korean J. Pain, 2020, 33(2), 108-120.
[http://dx.doi.org/10.3344/kjp.2020.33.2.108] [PMID: 32235011]
[45]
Auvenshine, R.C. Acute vs. chronic pain. Tex. Dent. J., 2000, 117(7), 14-20.
[PMID: 11858059]
[46]
Souza Monteiro de Araujo, D.; Nassini, R.; Geppetti, P.; De Logu, F. TRPA1 as a therapeutic target for nociceptive pain. Expert Opin. Ther. Targets, 2020, 24(10), 997-1008.
[http://dx.doi.org/10.1080/14728222.2020.1815191] [PMID: 32838583]
[47]
McHugh, J.M.; McHugh, W.B. Pain: Neuroanatomy, chemical mediators, and clinical implications. AACN Clin. Issues, 2000, 11(2), 168-178.
[http://dx.doi.org/10.1097/00044067-200005000-00003] [PMID: 11235429]
[48]
Quintão, N.L.M.; Medeiros, R.; Santos, A.R.S.; Campos, M.M.; Calixto, J.B. The effects of diacerhein on mechanical allodynia in inflammatory and neuropathic models of nociception in mice. Anesth. Analg., 2005, 101(6), 1763-1769.
[http://dx.doi.org/10.1213/01.ane.0000184182.03203.61] [PMID: 16301256]
[49]
D’Agostino, G.; La Rana, G.; Russo, R. Acute intracerebroventricular administration of palmitoylethanolamide, an endogenous peroxi-some proliferator-activated receptor-α agonist, modulates carrageenan-induced paw edema in mice. J. Pharmacol. Exp. Ther., 2007, 322(3), 1137-1143.
[http://dx.doi.org/10.1124/jpet.107.123265] [PMID: 17565008]
[50]
Martins, M.A.; de Castro Bastos, L.; Tonussi, C.R. Formalin injection into knee joints of rats: Pharmacologic characterization of a deep somatic nociceptive model. J. Pain, 2006, 7(2), 100-107.
[http://dx.doi.org/10.1016/j.jpain.2005.09.002] [PMID: 16459275]
[51]
Hunskaar, S.; Hole, K. The formalin test in mice: Dissociation between inflammatory and non-inflammatory pain. Pain, 1987, 30(1), 103-114.
[http://dx.doi.org/10.1016/0304-3959(87)90088-1] [PMID: 3614974]
[52]
Zúñiga-Romero, A.; Ponce-Chávez, M.K.; Gauthereau-Torres, M.Y.; Ortega-Varela, L.F. Combination of diacerhein and antiepileptic drugs after local peripheral, and oral administration in the rat formalin test. Drug Dev. Res., 2014, 75(8), 510-520.
[http://dx.doi.org/10.1002/ddr.21232] [PMID: 25418935]
[53]
Gadotti, V.M.; Martins, D.F.; Pinto, H.F. Diacerein decreases visceral pain through inhibition of glutamatergic neurotransmission and cytokine signaling in mice. Pharmacol. Biochem. Behav., 2012, 102(4), 549-554.
[http://dx.doi.org/10.1016/j.pbb.2012.06.018] [PMID: 22750064]
[54]
Collier, H.O.; Dinneen, L.C.; Johnson, C.A.; Schneider, C. The abdominal constriction response and its suppression by analgesic drugs in the mouse. Br. J. Pharmacol. Chemother., 1968, 32(2), 295-310.
[http://dx.doi.org/10.1111/j.1476-5381.1968.tb00973.x] [PMID: 4230818]
[55]
Ribeiro, R.A.; Vale, M.L.; Thomazzi, S.M. Involvement of resident macrophages and mast cells in the writhing nociceptive response in-duced by zymosan and acetic acid in mice. Eur. J. Pharmacol., 2000, 387(1), 111-118.
[http://dx.doi.org/10.1016/S0014-2999(99)00790-6] [PMID: 10633169]
[56]
Brederson, J.D.; Kym, P.R.; Szallasi, A. Targeting TRP channels for pain relief. Eur. J. Pharmacol., 2013, 716(1-3), 61-76.
[http://dx.doi.org/10.1016/j.ejphar.2013.03.003] [PMID: 23500195]
[57]
da Silva, M.D.; Cidral-Filho, F.J.; Winkelmann-Duarte, E.C. Diacerein reduces joint damage, pain behavior and inhibits transient receptor potential vanilloid 1, matrix metalloproteinase and glial cells in rat spinal cord. Int. J. Rheum. Dis., 2017, 20(10), 1337-1349.
[http://dx.doi.org/10.1111/1756-185X.12741] [PMID: 26481104]
[58]
Herbert, M.K.; Holzer, P. Warum versagen substanz P (NK1)-rezeptorantagonisten in der schmerztherapie? Anaesthesist, 2002, 51(4), 308-319.
[http://dx.doi.org/10.1007/s00101-002-0296-7] [PMID: 12063723]
[59]
Izzo, A.A.; Mascolo, N.; Capasso, F. Effect of sodium rhein on electrically-evoked and agonist-induced contractions of the guinea-pig isolated ileal circular muscle. Br. J. Pharmacol., 1998, 124(4), 825-831.
[http://dx.doi.org/10.1038/sj.bjp.0701900] [PMID: 9690877]
[60]
Inoue, M.; Tokuyama, S.; Nakayamada, H.; Ueda, H. In vivo signal transduction of tetrodotoxin-sensitive nociceptive responses by substance P given into the planta of the mouse hind limb. Cell. Mol. Neurobiol., 1998, 18(5), 555-561.
[http://dx.doi.org/10.1023/A:1026335611162] [PMID: 9777254]
[61]
Nieto, F.R.; Cobos, E.J.; Tejada, M.Á.; Sánchez-Fernández, C.; González-Cano, R.; Cendán, C.M. Tetrodotoxin (TTX) as a therapeutic agent for pain. Mar. Drugs, 2012, 10(2), 281-305.
[http://dx.doi.org/10.3390/md10020281] [PMID: 22412801]
[62]
Wozniak, K.M.; Rojas, C.; Wu, Y.; Slusher, B.S. The role of glutamate signaling in pain processes and its regulation by GCP II inhibition. Curr. Med. Chem., 2012, 19(9), 1323-1334.
[http://dx.doi.org/10.2174/092986712799462630] [PMID: 22304711]
[63]
Du, J.; Koltzenburg, M.; Carlton, S.M. Glutamate-induced excitation and sensitization of nociceptors in rat glabrous skin. Pain, 2001, 89(2-3), 187-198.
[http://dx.doi.org/10.1016/S0304-3959(00)00362-6] [PMID: 11166475]
[64]
Wu, L-J.; Ko, S.W.; Zhuo, M. Kainate receptors and pain: From dorsal root ganglion to the anterior cingulate cortex. Curr. Pharm. Des., 2007, 13(15), 1597-1605.
[http://dx.doi.org/10.2174/138161207780765864] [PMID: 17504152]
[65]
Niswender, C.M.; Conn, P.J. Metabotropic glutamate receptors: Physiology, pharmacology, and disease. Annu. Rev. Pharmacol. Toxicol., 2010, 50, 295-322.
[http://dx.doi.org/10.1146/annurev.pharmtox.011008.145533] [PMID: 20055706]
[66]
Linden, D.J.; Smeyne, M.; Connor, J.A. Trans-ACPD, a metabotropic receptor agonist, produces calcium mobilization and an inward current in cultured cerebellar Purkinje neurons. J. Neurophysiol., 1994, 71(5), 1992-1998.
[http://dx.doi.org/10.1152/jn.1994.71.5.1992] [PMID: 8064363]
[67]
Viviani, B.; Bartesaghi, S.; Gardoni, F. Interleukin-1β enhances NMDA receptor-mediated intracellular calcium increase through activa-tion of the Src family of kinases. J. Neurosci., 2003, 23(25), 8692-8700.
[http://dx.doi.org/10.1523/JNEUROSCI.23-25-08692.2003] [PMID: 14507968]
[68]
Cury, Y.; Picolo, G.; Gutierrez, V.P.; Ferreira, S.H. Pain and analgesia: The dual effect of nitric oxide in the nociceptive system. Nitric Oxide, 2011, 25(3), 243-254.
[http://dx.doi.org/10.1016/j.niox.2011.06.004] [PMID: 21723953]
[69]
Durate, I.D.; Lorenzetti, B.B.; Ferreira, S.H. Peripheral analgesia and activation of the nitric oxide-cyclic GMP pathway. Eur. J. Pharmacol., 1990, 186(2-3), 289-293.
[http://dx.doi.org/10.1016/0014-2999(90)90446-D] [PMID: 1981187]
[70]
Ferreira, S.H.; Duarte, I.D.G.; Lorenzetti, B.B. The molecular mechanism of action of peripheral morphine analgesia: Stimulation of the cGMP system via nitric oxide release. Eur. J. Pharmacol., 1991, 201(1), 121-122.
[http://dx.doi.org/10.1016/0014-2999(91)90333-L] [PMID: 1665419]
[71]
Pavelka, K.; Bruyère, O.; Cooper, C. Diacerein: Benefits, risks and place in the management of osteoarthritis. An opinion-based report from the ESCEO. Drugs Aging, 2016, 33(2), 75-85.
[http://dx.doi.org/10.1007/s40266-016-0347-4] [PMID: 26849131]
[72]
Tamura, T.; Ohmori, K. Diacerein suppresses the increase in plasma nitric oxide in rat adjuvant-induced arthritis. Eur. J. Pharmacol., 2001, 419(2-3), 269-274.
[http://dx.doi.org/10.1016/S0014-2999(01)00990-6] [PMID: 11426851]
[73]
Dohrn, C.S.; Beitz, A.J. NMDA receptor mRNA expression in NOS-containing neurons in the spinal trigeminal nucleus of the rat. Neurosci. Lett., 1994, 175(1-2), 28-32.
[http://dx.doi.org/10.1016/0304-3940(94)91070-7] [PMID: 7526293]
[74]
Fan, W.; Huang, F.; Wu, Z.; Zhu, X.; Li, D.; He, H. The role of nitric oxide in orofacial pain. Nitric Oxide, 2012, 26(1), 32-37.
[http://dx.doi.org/10.1016/j.niox.2011.11.003] [PMID: 22138296]
[75]
Salter, D.M.; Wright, M.O.; Millward-Sadler, S.J. NMDA receptor expression and roles in human articular chondrocyte mechanotransduction. Biorheology, 2004, 41(3-4), 273-281.
[PMID: 15299260]
[76]
Lakhan, SE; Avramut, M Matrix metalloproteinases in neuropathic pain and migraine: Friends, enemies, and therapeutic targets. Pain Res Treat, 2012, 2012
[77]
Kawasaki, Y.; Xu, Z.Z.; Wang, X. Distinct roles of matrix metalloproteases in the early- and late-phase development of neuropathic pain. Nat. Med., 2008, 14(3), 331-336.
[http://dx.doi.org/10.1038/nm1723] [PMID: 18264108]
[78]
Tamura, T.; Kosaka, N.; Ishiwa, J.; Sato, T.; Nagase, H.; Ito, A. Rhein, an active metabolite of diacerein, down-regulates the production of pro-matrix metalloproteinases-1, -3, -9 and -13 and up-regulates the production of tissue inhibitor of metalloproteinase-1 in cultured rabbit ar-ticular chondrocytes. Osteoarthritis Cartilage, 2001, 9(3), 257-263.
[http://dx.doi.org/10.1053/joca.2000.0383] [PMID: 11300749]
[79]
Wang, Y.; Fan, X.; Tang, T. Rhein and rhubarb similarly protect the blood-brain barrier after experimental traumatic brain injury via gp91phox subunit of NADPH oxidase/ROS/ERK/MMP-9 signaling pathway. Sci. Rep., 2016, 6, 37098.
[http://dx.doi.org/10.1038/srep37098] [PMID: 27901023]
[80]
Tien, P.T.; Lin, C.H.; Chen, C.S. Diacerein inhibits myopia progression through lowering inflammation in retinal pigment epithelial cell. Mediators Inflamm., 2021, 2021, 6660640.
[http://dx.doi.org/10.1155/2021/6660640] [PMID: 34285659]
[81]
Obara, I.; Telezhkin, V.; Alrashdi, I.; Chazot, P.L. Histamine, histamine receptors, and neuropathic pain relief. Br. J. Pharmacol., 2020, 177(3), 580-599.
[http://dx.doi.org/10.1111/bph.14696] [PMID: 31046146]
[82]
Autore, G.; Caliendo, G.; Pepe, A.; Capasso, F. Perfusion of rat colon with sennosides, rhein and rheinanthrone. Concentration-related hista-mine release. Eur. J. Pharmacol., 1990, 191(1), 97-99.
[http://dx.doi.org/10.1016/0014-2999(90)94101-3] [PMID: 1709407]
[83]
Tamura, T.; Shirai, T.; Kosaka, N.; Ohmori, K.; Takafumi, N. Pharmacological studies of diacerein in animal models of inflammation, arthritis and bone resorption. Eur. J. Pharmacol., 2002, 448(1), 81-87.
[http://dx.doi.org/10.1016/S0014-2999(02)01898-8] [PMID: 12126975]
[84]
Leung, L.; Cahill, C.M. TNF-α and neuropathic pain--a review. J. Neuroinflammation, 2010, 7, 27.
[http://dx.doi.org/10.1186/1742-2094-7-27] [PMID: 20398373]
[85]
Hess, A.; Axmann, R.; Rech, J. Blockade of TNF-α rapidly inhibits pain responses in the central nervous system. Proc. Natl. Acad. Sci. USA, 2011, 108(9), 3731-3736.
[http://dx.doi.org/10.1073/pnas.1011774108] [PMID: 21245297]
[86]
Ren, K.; Torres, R. Role of interleukin-1β during pain and inflammation. Brain Res. Brain Res. Rev., 2009, 60(1), 57-64.
[http://dx.doi.org/10.1016/j.brainresrev.2008.12.020] [PMID: 19166877]
[87]
Ge, H.; Tang, H.; Liang, Y. Rhein attenuates inflammation through inhibition of NF-κB and NALP3 inflammasome in vivo and in vitro. Drug Des. Devel. Ther., 2017, 11, 1663-1671.
[http://dx.doi.org/10.2147/DDDT.S133069] [PMID: 28652704]
[88]
Petrosino, S.; Ahmad, A.; Marcolongo, G. Diacerein is a potent and selective inhibitor of palmitoylethanolamide inactivation with anal-gesic activity in a rat model of acute inflammatory pain. Pharmacol. Res., 2015, 91, 9-14.
[http://dx.doi.org/10.1016/j.phrs.2014.10.008] [PMID: 25447594]
[89]
Mendes, A.F.; Caramona, M.M.; de Carvalho, A.P.; Lopes, M.C. Diacerhein and rhein prevent interleukin-1β-induced nuclear factor-kappaB activation by inhibiting the degradation of inhibitor kappaB-α. Pharmacol. Toxicol., 2002, 91(1), 22-28.
[http://dx.doi.org/10.1034/j.1600-0773.2002.910104.x] [PMID: 12193257]
[90]
Yu, C.; Qi, D.; Sun, J.F.; Li, P.; Fan, H.Y. Rhein prevents endotoxin-induced acute kidney injury by inhibiting NF-κB activities. Sci. Rep., 2015, 5, 11822.
[http://dx.doi.org/10.1038/srep11822] [PMID: 26149595]
[91]
Kawabata, A. Prostaglandin E2 and pain--an update. Biol. Pharm. Bull., 2011, 34(8), 1170-1173.
[http://dx.doi.org/10.1248/bpb.34.1170] [PMID: 21804201]
[92]
Almezgagi, M.; Zhang, Y.; Hezam, K. Diacerein: Recent insight into pharmacological activities and molecular pathways. Biomed. Pharmacother., 2020, 131, 110594.
[http://dx.doi.org/10.1016/j.biopha.2020.110594] [PMID: 32858499]
[93]
Álvarez-Soria, M.A.; Herrero-Beaumont, G.; Sánchez-Pernaute, O.; Bellido, M.; Largo, R. Diacerein has a weak effect on the catabolic pathway of human osteoarthritis synovial fibroblast--comparison to its effects on osteoarthritic chondrocytes. Rheumatology (Oxford), 2008, 47(5), 627-633.
[http://dx.doi.org/10.1093/rheumatology/ken116] [PMID: 18375401]
[94]
Martel-Pelletier, J.; Pelletier, J.P. Effects of diacerein at the molecular level in the osteoarthritis disease process. Ther. Adv. Musculoskelet. Dis., 2010, 2(2), 95-104.
[http://dx.doi.org/10.1177/1759720X09359104] [PMID: 22870441]
[95]
Yuan, Y.; Zheng, J.; Wang, M.; Li, Y.; Ruan, J.; Zhang, H. Metabolic activation of rhein: Insights into the potential toxicity induced by rhein-containing herbs. J. Agric. Food Chem., 2016, 64(28), 5742-5750.
[http://dx.doi.org/10.1021/acs.jafc.6b01872] [PMID: 27362917]
[96]
Bironaite, D.; Ollinger, K. The hepatotoxicity of rhein involves impairment of mitochondrial functions. Chem. Biol. Interact., 1997, 103(1), 35-50.
[http://dx.doi.org/10.1016/S0009-2797(96)03747-7] [PMID: 9051122]
[97]
He, L.N.; Yang, A.H.; Cui, T.Y. Reactive metabolite activation by CYP2C19-mediated rhein hepatotoxicity. Xenobiotica, 2015, 45(4), 361-372.
[http://dx.doi.org/10.3109/00498254.2014.984794] [PMID: 25815638]
[98]
Leite, N.C.; Viegas, B.B.; Villela-Nogueira, C.A.; Carlos, F.O.; Cardoso, C.R.L.; Salles, G.F. Efficacy of diacerein in reducing liver steatosis and fibro-sis in patients with type 2 diabetes and non-alcoholic fatty liver disease: A randomized, placebo-controlled trial. Diabetes Obes. Metab., 2019, 21(5), 1266-1270.
[http://dx.doi.org/10.1111/dom.13643] [PMID: 30687994]
[99]
Yang, D.; Huang, W.Y.; Li, Y.Q. Acute and subchronic toxicity studies of rhein in immature and d-galactose-induced aged mice and its potential hepatotoxicity mechanisms. Drug Chem. Toxicol., 2020, 1-12.
[http://dx.doi.org/10.1080/01480545.2020.1809670] [PMID: 32842782]
[100]
Renan, X.; Lepage, M.; Connan, D. Case report of fatal hepatitis from diacerein. Therapie, 2001, 56(2), 190-191.
[PMID: 11471374]

Rights & Permissions Print Cite
Article Metrics
1
© 2024 Bentham Science Publishers | Privacy Policy