Login Register Cart 0
Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

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

Emodin Reduces Inflammatory and Nociceptive Responses in Different Pain-and Inflammation-Induced Mouse Models

Author(s): Xiuli Zhang, Jing Li* and Lili Guan

Volume 26, Issue 5, 2023

Published on: 03 September, 2022

Page: [989 - 1000] Pages: 12

DOI: 10.2174/1386207325666220514145252

Price: $65

Abstract

Aims: Different nociceptive models induced with heat and chemicals were used to assess the potency of emodin in alleviating pain. The anti-inflammatory properties of emodin at different doses were also assessed using different anti-inflammatory in vivo models.

Objective: Pain management is a global problem nowadays, and nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed to assuage inflammation and alleviate pain. Prolonged usage of these NSAIDs triggers various adverse drug reactions (ADRs). The dose-dependent effect of emodin was assessed by treating mice with three different doses (5, 10, and 20 mg/kg bwt) of emodin.

Methods: The effects of emodin in various nociceptive and inflammatory models were assessed. The anti-nociceptive potential of emodin was evaluated with the hot plate and tail immersion tests. The effects of emodin on acetic acid-, glutamate-, capsaicin-, and formalin-stimulated pain models were examined. The anti-inflammatory potency of emodin was examined in a carrageenan-induced inflammatory model. The sedative effect of emodin was assessed by an open field test.

Results: Emodin potentially prevented the nociception provoked by thermal stressors during the hot plate and tail immersion methods and from chemical stressors such as acetic acid, formalin, capsaicin, and glutamate. The anti-inflammatory action of emodin was evidenced by carrageenaninduced paw edema and peritoneal leukocyte penetration. The open field results confirmed that emodin induced a mild sedative effect on the treated mice.

Conclusion: Our overall results obtained from this study confirmed that emodin exhibits potent anti- nociceptive and anti-inflammatory effects.

Keywords: Phytomedicine, emodin, nociception, inflammation, customary drugs, pain management.

« Previous Next »
Graphical Abstract

[1]
Mantovani, A. Molecular pathways linking inflammation and cancer. Curr. Mol. Med., 2010, 10(4), 369-373.
[http://dx.doi.org/10.2174/156652410791316968] [PMID: 20455855]
[2]
Obreja, O.; Rathee, P.K.; Lips, K.S.; Distler, C.; Kress, M. IL-1 beta potentiates heat-activated currents in rat sensory neurons: Involvement of IL-1RI, tyrosine kinase, and protein kinase C. FASEB J., 2002, 16(12), 1497-1503.
[http://dx.doi.org/10.1096/fj.02-0101com] [PMID: 12374772]
[3]
Olesen, A.E.; Andresen, T.; Staahl, C.; Drewes, A.M. Human experimental pain models for assessing the therapeutic efficacy of analgesic drugs. Pharmacol. Rev., 2012, 64(3), 722-779.
[http://dx.doi.org/10.1124/pr.111.005447] [PMID: 22722894]
[4]
Gudes, S.; Barkai, O.; Caspi, Y.; Katz, B.; Lev, S.; Binshtok, A.M. The role of slow and persistent TTX-resistant sodium currents in acute tumor necrosis factor-α-mediated increase in nociceptors excitability. J. Neurophysiol., 2015, 113(2), 601-619.
[http://dx.doi.org/10.1152/jn.00652.2014] [PMID: 25355965]
[5]
Al-Saeed, A. Gastrointestinal and cardiovascular risk of nonsteroidal anti-inflammatory drugs. Oman Med. J., 2011, 26(6), 385-391.
[http://dx.doi.org/10.5001/omj.2011.101] [PMID: 22253945]
[6]
Krotz, F.; Schiele, T.M.; Klauss, V.; Sohn, H.Y. Selective COX-2 inhibitors and risk of myocardial infarction. J. Vasc. Res., 2005, 42(4), 312-324.
[http://dx.doi.org/10.1159/000086459] [PMID: 15976506]
[7]
Rostom, A.; Dube, C.; Wells, G.; Tugwell, P.; Welch, V.; Jolicoeur, E.; McGowan, J. Prevention of NSAID-induced gastroduodenal ulcers. Cochrane Database Syst. Rev., 2002, 4(4), CD002296.
[PMID: 12519573]
[8]
Russell, R.I. Non-steroidal anti-inflammatory drugs and gastrointestinal damage-problems and solutions. Postgrad. Med. J., 2001, 77(904), 82-88.
[http://dx.doi.org/10.1136/pmj.77.904.82] [PMID: 11161072]
[9]
Vonkeman, H.E.; Brouwers, J.R.; van de Laar, M.A. Understanding the NSAID related risk of vascular events. BMJ, 2006, 332(7546), 895-898.
[http://dx.doi.org/10.1136/bmj.332.7546.895] [PMID: 16613964]
[10]
Essex, M.N.; Zhang, R.Y.; Berger, M.F.; Upadhyay, S.; Park, P.W. Safety of celecoxib compared with placebo and non-selective NSAIDs: Cumulative meta-analysis of 89 randomized controlled trials. Expert Opin. Drug Saf., 2013, 12(4), 465-477.
[http://dx.doi.org/10.1517/14740338.2013.780595] [PMID: 23506230]
[11]
Sehajpal, S.; Prasad, D.N.; Singh, R.K. Prodrugs of non-steroidal anti-inflammatory drugs (NSAIDs): A long march towards synthesis of safer NSAIDs. Mini Rev. Med. Chem., 2018, 18(14), 1199-1219.
[http://dx.doi.org/10.2174/1389557518666180330112416] [PMID: 29600762]
[12]
Wang, M.; Zhao, R.; Wang, W.; Mao, X.; Yu, J. Lipid regulation effects of Polygoni Multiflori Radix, its processed products and its major substances on steatosis human liver cell line L02. J. Ethnopharmacol., 2012, 139(1), 287-293.
[http://dx.doi.org/10.1016/j.jep.2011.11.022] [PMID: 22120683]
[13]
Wang, Z.M.; Zhu, S.G.; Wu, Z.W.; Lu, Y.; Fu, H.Z.; Qian, R.Q. Kirenol upregulates nuclear annexin-1 which interacts with NF-κB to attenuate synovial inflammation of collagen-induced arthritis in rats. J. Ethnopharmacol., 2011, 137(1), 774-782.
[http://dx.doi.org/10.1016/j.jep.2011.06.037] [PMID: 21745559]
[14]
Lee, M.H.; Kao, L.; Lin, C.C. Comparison of the antioxidant and transmembrane permeative activities of the different Polygonum cuspidatum extracts in phospholipid-based microemulsions. J. Agric. Food Chem., 2011, 59(17), 9135-9141.
[http://dx.doi.org/10.1021/jf201577f] [PMID: 21770401]
[15]
Naqvi, S.; Ullah, M.F.; Hadi, S.M. DNA degradation by aqueous extract of Aloe vera in the presence of copper ions. Indian J. Biochem. Biophys., 2010, 47(3), 161-165.
[PMID: 20653287]
[16]
Turner, R.A.; Turner, R.; Ebborn, P. Analgesics: Screening methods in pharmacology; Academic Press: New York, 1965.
[17]
Uma Devi, P.; Ganasoundari, A.; Rao, B.S.; Srinivasan, K.K. In vivo radioprotection by ocimum flavonoids: Survival of mice. Radiat. Res., 1999, 151(1), 74-78.
[http://dx.doi.org/10.2307/3579750] [PMID: 9973087]
[18]
Koster, R.; Anderson, M.; De Beer, E.J. Acetic acid analgesic screening. Fed. Proc., 1959, 18, 412.
[19]
Beirith, A.; Santos, A.R.; Calixto, J.B. Mechanisms underlying the nociception and paw oedema caused by injection of glutamate into the mouse paw. Brain Res., 2002, 924(2), 219-228.
[http://dx.doi.org/10.1016/S0006-8993(01)03240-1] [PMID: 11750907]
[20]
Luiz, A.P.; Moura, J.D.; Meotti, F.C.; Guginski, G.; Guimarães, C.L.; Azevedo, M.S.; Rodrigues, A.L.; Santos, A.R. Antinociceptive action of ethanolic extract obtained from roots of Humirianthera ampla Miers. J. Ethnopharmacol., 2007, 114(3), 355-363.
[http://dx.doi.org/10.1016/j.jep.2007.08.016] [PMID: 17900839]
[21]
Hunskaar, S.; Fasmer, O.B.; Hole, K. Formalin test in mice, a useful technique for evaluating mild analgesics. J. Neurosci. Methods, 1985, 14(1), 69-76.
[http://dx.doi.org/10.1016/0165-0270(85)90116-5] [PMID: 4033190]
[22]
Passos, G.F.; Fernandes, E.S.; da Cunha, F.M.; Ferreira, J.; Pianowski, L.F.; Campos, M.M.; Calixto, J.B. Anti-inflammatory and anti-allergic properties of the essential oil and active compounds from Cordia verbenacea. J. Ethnopharmacol., 2007, 110(2), 323-333.
[http://dx.doi.org/10.1016/j.jep.2006.09.032] [PMID: 17084568]
[23]
Vinegar, R.; Truax, J.F.; Selph, J.L. Some quantitative temporal characteristics of carrageenin-induced pleurisy in the rat. Proc. Soc. Exp. Biol. Med., 1973, 143(3), 711-714.
[http://dx.doi.org/10.3181/00379727-143-37397] [PMID: 4719457]
[24]
Edwards, J.C.; Sedgwick, A.D.; Willoughby, D.A. The formation of a structure with the features of synovial lining by subcutaneous injection of air: An in vivo tissue culture system. J. Pathol., 1981, 134(2), 147-156.
[http://dx.doi.org/10.1002/path.1711340205] [PMID: 7019400]
[25]
Hiruma-Lima, C.A.; Gracioso, J.S.; Bighetti, E.J.B.; Germonsén Robineou, L.; Souza Brito, A.R. The juice of fresh leaves of Boerhaavia diffusa L. (Nyctaginaceae) markedly reduces pain in mice. J. Ethnopharmacol., 2000, 71(1-2), 267-274.
[http://dx.doi.org/10.1016/S0378-8741(00)00178-1] [PMID: 10904173]
[26]
Srinivasan, K.; Muruganandan, S.; Lal, J.; Chandra, S.; Tandan, S.K.; Raviprakash, V.; Kumar, D. Antinociceptive and antipyretic activities of Pongamia pinnata leaves. Phytother. Res., 2003, 17(3), 259-264.
[http://dx.doi.org/10.1002/ptr.1126] [PMID: 12672157]
[27]
Wilder-Smith, C.H. The balancing act: Endogenous modulation of pain in functional gastrointestinal disorders. Gut, 2011, 60(11), 1589-1599.
[http://dx.doi.org/10.1136/gutjnl-2011-300253] [PMID: 21768212]
[28]
Johnson, A.C.; Greenwood-Van Meerveld, B. Stress-induced pain: A target for the development of novel therapeutics. J. Pharmacol. Exp. Ther., 2014, 351(2), 327-335.
[http://dx.doi.org/10.1124/jpet.114.218065] [PMID: 25194019]
[29]
Sehajpal, S.; Prasad, D.N.; Singh, R.K. Novel ketoprofen-antioxidants mutual codrugs as safer nonsteroidal anti-inflammatory drugs: Synthesis, kinetic and pharmacological evaluation. Arch. Pharm. (Weinheim), 2019, 352(7), e1800339.
[http://dx.doi.org/10.1002/ardp.201800339]
[30]
Ferreira, R.T.; Coutinho, M.A.S.; Malvar, D.C.; Costa, E.A.; Florentino, I.F.; Costa, S.S.; Vanderlinde, F.A. Mechanisms under lying the antinociceptive, antidematogenic, andanti-inflammatory activity of the main flavonoid from Ka-lanchoepinnata. Evid. Based Complement. Alternat. Med., 2014, 2014, 429256.
[http://dx.doi.org/10.1155/2014/429256] [PMID: 25580151]
[31]
Hasan, M.M.; Uddin, N.; Hasan, M.R.; Islam, A.F.; Hossain, M.M.; Rahman, A.B.; Hossain, M.S.; Chowdhury, I.A.; Rana, M.S. Analgesic and anti-inflammatory activities of leaf extract of Mallotus repandus (Willd.) Muell. Arg. BioMed Res. Int., 2014, 2014, 539807.
[http://dx.doi.org/10.1155/2014/539807] [PMID: 25629031]
[32]
Sawynok, J.; Reid, A.; Meisner, J. Pain behaviors produced by capsaicin: Influence of inflammatory mediators and nerve injury. J. Pain, 2006, 7(2), 134-141.
[http://dx.doi.org/10.1016/j.jpain.2005.09.013] [PMID: 16459279]
[33]
Mo, G.; Bernier, L.P.; Zhao, Q.; Chabot-Doré, A.J.; Ase, A.R.; Logothetis, D.; Cao, C.Q.; Séguéla, P. Subtype-specific regulation of P2X3 and P2X2/3 receptors by phosphoinositides in peripheral nociceptors. Mol. Pain 2009, 5(5:47), 47.
[http://dx.doi.org/10.1186/1744-8069-5-47]
[34]
Gao, Y.; Liu, H.; Deng, L.; Zhu, G.; Xu, C.; Li, G.; Liu, S.; Xie, J.; Liu, J.; Kong, F.; Wu, R.; Li, G.; Liang, S. Effect of emodin on neuropathic pain transmission mediated by P2X2/3 receptor of primary sensory neurons. Brain Res. Bull., 2011, 84(6), 406-413.
[http://dx.doi.org/10.1016/j.brainresbull.2011.01.017] [PMID: 21303687]
[35]
Malmberg, A.B.; Yaksh, T.L. Cyclooxygenase inhibition and the spinal release of prostaglandin E2 and amino acids evoked by paw formalin injection: A microdialysis study in unanesthetized rats. J. Neurosci., 1995, 15(4), 2768-2776.
[http://dx.doi.org/10.1523/JNEUROSCI.15-04-02768.1995] [PMID: 7722627]
[36]
McNamara, C.R.; Mandel-Brehm, J.; Bautista, D.M.; Siemens, J.; Deranian, K.L.; Zhao, M.; Hayward, N.J.; Chong, J.A.; Julius, D.; Moran, M.M.; Fanger, C.M. TRPA1 mediates formalin-induced pain. Proc. Natl. Acad. Sci. USA, 2007, 104(33), 13525-13530.
[http://dx.doi.org/10.1073/pnas.0705924104] [PMID: 17686976]
[37]
Verri, W.A., Jr; Cunha, T.M.; Parada, C.A.; Poole, S.; Cunha, F.Q.; Ferreira, S.H. Hypernociceptive role of cytokines and chemokines: Targets for analgesic drug development? Pharmacol. Ther., 2006, 112(1), 116-138.
[http://dx.doi.org/10.1016/j.pharmthera.2006.04.001] [PMID: 16730375]
[38]
Zarpelon, A.C.; Cunha, T.M.; Alves-Filho, J.C.; Pinto, L.G.; Ferreira, S.H.; McInnes, I.B.; Xu, D.; Liew, F.Y.; Cunha, F.Q.; Verri, W.A., Jr IL-33/ST2 signalling contributes to carrageenin-induced innate inflammation and inflammatory pain: Role of cytokines, endothelin-1 and prostaglandin E2. Br. J. Pharmacol., 2013, 169(1), 90-101.
[http://dx.doi.org/10.1111/bph.12110] [PMID: 23347081]
[39]
Schomberg, D.; Olson, J.K. Immune responses of microglia in the spinal cord: Contribution to pain states. Exp. Neurol., 2012, 234(2), 262-270.
[http://dx.doi.org/10.1016/j.expneurol.2011.12.021] [PMID: 22226600]
[40]
Taves, S.; Berta, T.; Chen, G.; Ji, R.R. Microglia and spinal cord synaptic plasticity in persistent pain. Neural Plast., 2013, 2013, 753656.
[http://dx.doi.org/10.1155/2013/753656] [PMID: 24024042]
[41]
Prado, W.A.; Schiavon, V.F.; Cunha, F.Q. Dual effect of local application of nitric oxide donors in a model of incision pain in rats. Eur. J. Pharmacol., 2002, 441(1-2), 57-65.
[http://dx.doi.org/10.1016/S0014-2999(02)01413-9] [PMID: 12007920]
[42]
Kim, D.Y.; Kang, T.B.; Shim, D.W.; Sun, X.; Han, J.W.; Ji, Y.E.; Kim, T.J.; Koppula, S.; Lee, K.H. Emodin attenuates A23187-induced mast cell degranulation and tumor necrosis factor-α secretion through protein kinase C and IκB kinase 2 signaling. Eur. J. Pharmacol., 2014, 723, 501-506.
[http://dx.doi.org/10.1016/j.ejphar.2013.09.066] [PMID: 24239713]

Rights & Permissions Print Cite
Article Metrics
5
© 2024 Bentham Science Publishers | Privacy Policy