Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Natural Product Inhibitors of Cyclooxygenase (COX) Enzyme: A Review on Current Status and Future Perspectives

Author(s): Goutami G. Ambati and Sanjay M. Jachak*

Volume 28, Issue 10, 2021

Published on: 02 June, 2020

Page: [1877 - 1905] Pages: 29

DOI: 10.2174/0929867327666200602131100

Price: $65

conference banner
Abstract

Background: Several clinically used COX-1 and COX-2 inhibitor drugs were reported to possess severe side effects like GI ulcers and cardiovascular disturbances, respectively. Natural products being structurally diverse always attracted the attention of chemists/ medicinal chemists as a potential source of lead molecules in the drug discovery process. COX-2 inhibitory natural products also possess potential cancer chemopreventive property against various cancers including that of colon, breast and prostate.

Methods: Various in vitro, in vivo and in silico standardized methods were used to evaluate COX inhibition property of different secondary metabolites isolated from plant, microbial and marine origin.

Results: We had earlier reported a detailed account of natural product inhibitors of COX reported during 1995-2005, in 2006. In the proposed review, we report 158 natural product inhibitors of COX during 2006 to 2019 belonging to various secondary metabolite classes such as alkaloids, terpenoids, polyphenols as flavonoids, chromones, coumarins, lignans, anthraquinones, naphthalenes, curcuminoids, diarylheptanoids and miscellaneous compounds of plant and marine origin. Further Structure Activity Relationship (SAR) studies of possible leads are also included in the article.

Conclusion: COX inhibitors served as a potential source of lead molecules for the discovery and development of anti-inflammatory drugs. Compilation of natural product and semisynthetic inhibitors of COX may serve as valuable information to the researchers who are looking for possible lead molecules from a natural source to conduct further preclinical and clinical studies.

Keywords: Cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), natural product COX inhibitors, antiinflammatory activity, cancer, secondary metabolites.

[1]
Hemler, M.; Lands, W.E. Purification of the cyclooxygenase that forms prostaglandins. Demonstration of two forms of iron in the holoenzyme. J. Biol. Chem., 1976, 251(18), 5575-5579.
[PMID: 823151]
[2]
Vane, J.R.; Botting, R.M. Anti-inflammatory drugs and their mechanism of action. Inflamm. Res., 1998, 47(Suppl. 2), S78-S87.
[http://dx.doi.org/10.1007/s000110050284] [PMID: 9831328]
[3]
Chandrasekharan, N.V.; Dai, H.; Roos, K.L.; Evanson, N.K.; Tomsik, J.; Elton, T.S.; Simmons, D.L. COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression. Proc. Natl. Acad. Sci. USA, 2002, 99(21), 13926-13931.
[http://dx.doi.org/10.1073/pnas.162468699] [PMID: 12242329]
[4]
Picot, D.; Loll, P.J.; Garavito, R.M. The X-ray crystal structure of the membrane protein prostaglandin H2 synthase-1. Nature, 1994, 367(6460), 243-249.
[http://dx.doi.org/10.1038/367243a0] [PMID: 8121489]
[5]
Perrone, M.G.; Scilimati, A.; Simone, L.; Vitale, P. Selective COX-1 inhibition: a therapeutic target to be reconsidered. Curr. Med. Chem., 2010, 17(32), 3769-3805.
[http://dx.doi.org/10.2174/092986710793205408] [PMID: 20858219]
[6]
Malhotra, S.; Deshmukh, S.S.; Dastidar, S.G. COX inhibitors for airway inflammation. Expert Opin. Ther. Targets, 2012, 16(2), 195-207.
[http://dx.doi.org/10.1517/14728222.2012.661416] [PMID: 22324934]
[7]
Simmons, D.L.; Botting, R.M.; Hla, T. Cyclooxygenase isozymes: the biology of prostaglandin synthesis and inhibition. Pharmacol. Rev., 2004, 56(3), 387-437.
[http://dx.doi.org/10.1124/pr.56.3.3] [PMID: 15317910]
[8]
Chandrasekharan, N.V.; Simmons, D.L. The cyclooxygenases. Genome Biol., 2004, 5(9), 241.
[http://dx.doi.org/10.1186/gb-2004-5-9-241] [PMID: 15345041]
[9]
Malkowski, M.G.; Ginell, S.L.; Smith, W.L.; Garavito, R.M. The productive conformation of arachidonic acid bound to prostaglandin synthase. Science, 2000, 289(5486), 1933-1937.
[http://dx.doi.org/10.1126/science.289.5486.1933] [PMID: 10988074]
[10]
Choi, S.H.; Aid, S.; Bosetti, F. The distinct roles of cyclooxygenase-1 and -2 in neuroinflammation: implications for translational research. Trends Pharmacol. Sci., 2009, 30(4), 174-181.
[http://dx.doi.org/10.1016/j.tips.2009.01.002] [PMID: 19269697]
[11]
Smith, C.J.; Zhang, Y.; Koboldt, C.M.; Muhammad, J.; Zweifel, B.S.; Shaffer, A.; Talley, J.J.; Masferrer, J.L.; Seibert, K.; Isakson, P.C. Pharmacological analysis of cyclooxygenase-1 in inflammation. Proc. Natl. Acad. Sci. USA, 1998, 95(22), 13313-13318.
[http://dx.doi.org/10.1073/pnas.95.22.13313] [PMID: 9789085]
[12]
Kang, Y.J.; Mbonye, U.R.; DeLong, C.J.; Wada, M.; Smith, W.L. Regulation of intracellular cyclooxygenase levels by gene transcription and protein degradation. Prog. Lipid Res., 2007, 46(2), 108-125.
[http://dx.doi.org/10.1016/j.plipres.2007.01.001] [PMID: 17316818]
[13]
Baba, H.; Kohno, T.; Moore, K.A.; Woolf, C.J. Direct activation of rat spinal dorsal horn neurons by prostaglandin E2. J. Neurosci., 2001, 21(5), 1750-1756.
[http://dx.doi.org/10.1523/JNEUROSCI.21-05-01750.2001] [PMID: 11222664]
[14]
Regulski, M.; Regulska, K.; Prukała, W.; Piotrowska, H.; Stanisz, B.; Murias, M. COX-2 inhibitors: a novel strategy in the management of breast cancer. Drug Discov. Today, 2016, 21(4), 598-615.
[http://dx.doi.org/10.1016/j.drudis.2015.12.003] [PMID: 26723915]
[15]
Warner, T.D.; Giuliano, F.; Vojnovic, I.; Bukasa, A.; Mitchell, J.A.; Vane, J.R. Nonsteroid drug selectivities for cyclo-oxygenase-1 rather than cyclo-oxygenase-2 are associated with human gastrointestinal toxicity: a full in vitro analysis. Proc. Natl. Acad. Sci. USA, 1999, 96(13), 7563-7568.
[http://dx.doi.org/10.1073/pnas.96.13.7563] [PMID: 10377455]
[16]
Oksuz, E.; Atalar, F.; Tanırverdi, G.; Bilir, A.; Shahzadi, A.; Yazici, Z. Therapeutic potential of cyclooxygenase-3 inhibitors in the management of glioblastoma. J. Neurooncol., 2016, 126(2), 271-278.
[http://dx.doi.org/10.1007/s11060-015-1976-x] [PMID: 26508095]
[17]
Jachak, S.M. Cyclooxygenase inhibitory natural products: current status. Curr. Med. Chem., 2006, 13(6), 659-678.
[http://dx.doi.org/10.2174/092986706776055698] [PMID: 16529558]
[18]
Mitchell, J.A.; Warner, T.D. COX isoforms in the cardiovascular system: understanding the activities of non-steroidal anti-inflammatory drugs. Nat. Rev. Drug Discov., 2006, 5(1), 75-86.
[http://dx.doi.org/10.1038/nrd1929] [PMID: 16485347]
[19]
Marnett, L.J. The COXIB experience: a look in the rearview mirror. Annu. Rev. Pharmacol. Toxicol., 2009, 49, 265-290.
[http://dx.doi.org/10.1146/annurev.pharmtox.011008.145638] [PMID: 18851701]
[20]
Woodcock, J. A difficult balance-pain management, drug safety, and the FDA. N. Engl. J. Med., 2009, 361(22), 2105-2107.
[http://dx.doi.org/10.1056/NEJMp0908913] [PMID: 19940297]
[21]
Chan, F.K. Primer: managing NSAID-induced ulcer complications-balancing gastrointestinal and cardiovascular risks. Nat. Clin. Pract. Gastroenterol. Hepatol., 2006, 3(10), 563-573.
[http://dx.doi.org/10.1038/ncpgasthep0610] [PMID: 17008926]
[22]
Pirlamarla, P.; Bond, R.M. FDA labeling of NSAIDs: review of nonsteroidal anti-inflammatory drugs in cardiovascular disease. Trends Cardiovasc. Med., 2016, 26(8), 675-680.
[http://dx.doi.org/10.1016/j.tcm.2016.04.011] [PMID: 27238053]
[23]
Morgan, S.L.; Baggott, J.E.; Moreland, L.; Desmond, R.; Kendrach, A.C. The safety of flavocoxid, a medical food, in the dietary management of knee osteoarthritis. J. Med. Food, 2009, 12(5), 1143-1148.
[http://dx.doi.org/10.1089/jmf.2008.0244] [PMID: 19857081]
[24]
Olsen, N.J.; Branch, V.K.; Jonnala, G.; Seskar, M.; Cooper, M. Phase 1, placebo-controlled, dose escalation trial of chicory root extract in patients with osteoarthritis of the hip or knee. BMC Musculoskelet. Disord., 2010, 11(1), 156.
[http://dx.doi.org/10.1186/1471-2474-11-156] [PMID: 20618964]
[25]
Saklani, A.; Kutty, S.K. Plant-derived compounds in clinical trials. Drug Discov. Today, 2008, 13(3-4), 161-171.
[http://dx.doi.org/10.1016/j.drudis.2007.10.010] [PMID: 18275914]
[26]
Harvey, A.L. Natural products in drug discovery. Drug Discov. Today, 2008, 13(19-20), 894-901.
[http://dx.doi.org/10.1016/j.drudis.2008.07.004] [PMID: 18691670]
[27]
Newman, D.J. Natural products as leads to potential drugs: an old process or the new hope for drug discovery? J. Med. Chem., 2008, 51(9), 2589-2599.
[http://dx.doi.org/10.1021/jm0704090] [PMID: 18393402]
[28]
Newman, D.J.; Cragg, G.M. Natural products as sources of new drugs from 1981 to 2014. J. Nat. Prod., 2016, 79(3), 629-661.
[http://dx.doi.org/10.1021/acs.jnatprod.5b01055] [PMID: 26852623]
[29]
Harvey, A.L.; Edrada-Ebel, R.; Quinn, R.J. The re-emergence of natural products for drug discovery in the genomics era. Nat. Rev. Drug Discov., 2015, 14(2), 111-129.
[http://dx.doi.org/10.1038/nrd4510] [PMID: 25614221]
[30]
Cragg, G.M.; Newman, D.J. Natural products: a continuing source of novel drug leads. Biochim. Biophys. Acta, 2013, 1830(6), 3670-3695.
[http://dx.doi.org/10.1016/j.bbagen.2013.02.008] [PMID: 23428572]
[31]
La Clair, J.J. Natural product mode of action (MOA) studies: a link between natural and synthetic worlds. Nat. Prod. Rep., 2010, 27(7), 969-995.
[http://dx.doi.org/10.1039/b909989c] [PMID: 20422068]
[32]
Bohlin, L.; Göransson, U.; Alsmark, C.; Wedén, C.; Backlund, A. Natural products in modern life science. Phytochem. Rev., 2010, 9(2), 279-301.
[http://dx.doi.org/10.1007/s11101-009-9160-6] [PMID: 20700376]
[33]
Chandel, P.; Rawal, R.K.; Kaur, R. Natural products and their derivatives as cyclooxygenase-2 inhibitors. Future Med. Chem., 2018, 10(20), 2471-2492.
[http://dx.doi.org/10.4155/fmc-2018-0120] [PMID: 30325206]
[34]
Attiq, A.; Jalil, J.; Husain, K.; Ahmad, W. Raging the war against inflammation with natural products. Front. Pharmacol., 2018, 9, 976.
[http://dx.doi.org/10.3389/fphar.2018.00976] [PMID: 30245627]
[35]
Shang, J.H.; Cai, X.H.; Feng, T.; Zhao, Y.L.; Wang, J.K.; Zhang, L.Y.; Yan, M.; Luo, X.D. Pharmacological evaluation of Alstonia scholaris: anti-inflammatory and analgesic effects. J. Ethnopharmacol., 2010, 129(2), 174-181.
[http://dx.doi.org/10.1016/j.jep.2010.02.011] [PMID: 20219658]
[36]
Muhammad, N.; Shrestha, R.L.; Adhikari, A.; Wadood, A.; Khan, H.; Khan, A.Z.; Maione, F.; Mascolo, N.; De Feo, V. First evidence of the analgesic activity of govaniadine, an alkaloid isolated from Corydalis govaniana Wall. Nat. Prod. Res., 2015, 29(5), 430-437.
[http://dx.doi.org/10.1080/14786419.2014.951933] [PMID: 25154594]
[37]
da Silva, K.A.; Manjavachi, M.N.; Paszcuk, A.F.; Pivatto, M.; Viegas, C., Jr; Bolzani, V.S.; Calixto, J.B. Plant derived alkaloid (-)-cassine induces anti-inflammatory and anti-hyperalgesics effects in both acute and chronic inflammatory and neuropathic pain models. Neuropharmacology, 2012, 62(2), 967-977.
[http://dx.doi.org/10.1016/j.neuropharm.2011.10.002] [PMID: 22032869]
[38]
Wang, H.; Liu, Y.; Zhang, J.; Xu, J.; Cui, C.A.; Guo, Y.; Jin, D.Q. 15-O-Acetyl-3-O-benzoylcharaciol and helioscopinolide A, two diterpenes isolated from Euphorbia helioscopia suppress microglia activation. Neurosci. Lett., 2016, 612, 149-154.
[http://dx.doi.org/10.1016/j.neulet.2015.12.010] [PMID: 26683904]
[39]
Yoon, J.H.; Lim, H.J.; Lee, H.J.; Kim, H.D.; Jeon, R.; Ryu, J.H. Inhibition of lipopolysaccharide-induced inducible nitric oxide synthase and cyclooxygenase-2 expression by xanthanolides isolated from Xanthium strumarium. Bioorg. Med. Chem. Lett., 2008, 18(6), 2179-2182.
[http://dx.doi.org/10.1016/j.bmcl.2007.12.076] [PMID: 18276135]
[40]
Abdelwahab, S.I.; Koko, W.S.; Taha, M.M.E.; Mohan, S.; Achoui, M.; Abdulla, M.A.; Mustafa, M.R.; Ahmad, S.; Noordin, M.I.; Yong, C.L.; Sulaiman, M.R.; Othman, R.; Hassan, A.A. In vitro and in vivo anti-inflammatory activities of columbin through the inhibition of cycloxygenase-2 and nitric oxide but not the suppression of NF-κB translocation. Eur. J. Pharmacol., 2012, 678(1-3), 61-70.
[http://dx.doi.org/10.1016/j.ejphar.2011.12.024] [PMID: 22227329]
[41]
Jayaprakasam, B.; Alexander-Lindo, R.L.; DeWitt, D.L.; Nair, M.G. Terpenoids from stinking toe (Hymeneae courbaril) fruits with cyclooxygenase and lipid peroxidation inhibitory activities. Food Chem., 2007, 105(2), 485-490.
[http://dx.doi.org/10.1016/j.foodchem.2007.04.004]
[42]
Hwangbo, C.; Lee, H.S.; Park, J.; Choe, J.; Lee, J.H. The anti-inflammatory effect of tussilagone, from Tussilago farfara, is mediated by the induction of heme oxygenase-1 in murine macrophages. Int. Immunopharmacol., 2009, 9(13-14), 1578-1584.
[http://dx.doi.org/10.1016/j.intimp.2009.09.016] [PMID: 19800419]
[43]
Eldeen, I.M.S.; Van Heerden, F.R.; Van Staden, J. Biological activities of cycloart-23-ene-3, 25-diol isolated from the leaves of Trichilia dregeana. S. Afr. J. Bot., 2007, 73(3), 366-371.
[http://dx.doi.org/10.1016/j.sajb.2007.02.192]
[44]
Siqueira, J.M. Jr.; Peters, R.R.; Gazola, A.C.; Krepsky, P.B.; Farias, M.R.; Rae, G.A.; de Brum-Fernandes, A.J.; Ribeiro-do-Valle, R.M. Anti-inflammatory effects of a triterpenoid isolated from Wilbrandia ebracteata Cogn. Life Sci., 2007, 80(15), 1382-1387.
[http://dx.doi.org/10.1016/j.lfs.2006.12.021] [PMID: 17286991]
[45]
Díaz-Viciedo, R.; Hortelano, S.; Girón, N.; Massó, J.M.; Rodriguez, B.; Villar, A.; de Las Heras, B. Modulation of inflammatory responses by diterpene acids from Helianthus annuus L. Biochem. Biophys. Res. Commun., 2008, 369(2), 761-766.
[http://dx.doi.org/10.1016/j.bbrc.2008.02.104] [PMID: 18313400]
[46]
Kang, O.H.; Chae, H.S.; Choi, J.G.; Oh, Y.C.; Lee, Y.S.; Kim, J.H.; Seung, M.J.; Jang, H.J.; Bae, K.H.; Lee, J.H.; Shin, D.W.; Kwon, D.Y. Ent-pimara-8(14), 15-dien-19-oic acid isolated from the roots of Aralia cordata inhibits induction of inflammatory mediators by blocking NF-kappaB activation and mitogen-activated protein kinase pathways. Eur. J. Pharmacol., 2008, 601(1-3), 179-185.
[http://dx.doi.org/10.1016/j.ejphar.2008.10.012] [PMID: 18938152]
[47]
Li, Y.C.; Xian, Y.F.; Ip, S.P.; Su, Z.R.; Su, J.Y.; He, J.J.; Xie, Q.F.; Lai, X.P.; Lin, Z.X. Anti-inflammatory activity of patchouli alcohol isolated from Pogostemonis herba in animal models. Fitoterapia, 2011, 82(8), 1295-1301.
[http://dx.doi.org/10.1016/j.fitote.2011.09.003] [PMID: 21958968]
[48]
Li, H.; Kim, J.Y.; Hyeon, J.; Lee, H.J.; Ryu, J.H. In vitro antiinflammatory activity of a new sesquiterpene lactone isolated from Siegesbeckia glabrescens. Phytother. Res., 2011, 25(9), 1323-1327.
[http://dx.doi.org/10.1002/ptr.3420] [PMID: 21308823]
[49]
Huang, G.J.; Pan, C.H.; Wu, C.H. Sclareol exhibits anti-inflammatory activity in both lipopolysaccharide-stimulated macrophages and the λ-carrageenan-induced paw edema model. J. Nat. Prod., 2012, 75(1), 54-59.
[http://dx.doi.org/10.1021/np200512a] [PMID: 22250858]
[50]
Gautam, R.; Jachak, S.M.; Saklani, A. Anti-inflammatory effect of Ajuga bracteosa Wall Ex Benth. mediated through cyclooxygenase (COX) inhibition. J. Ethnopharmacol., 2011, 133(2), 928-930.
[http://dx.doi.org/10.1016/j.jep.2010.11.003] [PMID: 21073945]
[51]
Hu, J.; Song, Y.; Mao, X.; Wang, Z.J.; Zhao, Q.J. Limonoids isolated from Toona sinensis and their radical scavenging, anti-inflammatory and cytotoxic activities. J. Funct. Foods, 2016, 20, 1-9.
[http://dx.doi.org/10.1016/j.jff.2015.10.009] [PMID: 32288789]
[52]
Zhang, J.L.; Chen, Z.H.; Xu, J.; Li, J.; Tan, Y.F.; Zhou, J.H.; Ye, W.C.; Tian, H.Y.; Jiang, R.W. New structures, chemotaxonomic significance and COX-2 inhibitory activities of cassane-type diterpenoids from the seeds of Caesalpinia minax. RSC. Adv., 2015, 5(93), 76567-76574.
[http://dx.doi.org/10.1039/C5RA14221K]
[53]
Cho, W.; Nam, J.W.; Kang, H.J.; Windono, T.; Seo, E.K.; Lee, K.T. Zedoarondiol isolated from the rhizoma of Curcuma heyneana is involved in the inhibition of iNOS, COX-2 and pro-inflammatory cytokines via the downregulation of NF-kappaB pathway in LPS-stimulated murine macrophages. Int. Immunopharmacol., 2009, 9(9), 1049-1057.
[http://dx.doi.org/10.1016/j.intimp.2009.04.012] [PMID: 19398040]
[54]
An, H.J.; Kim, I.T.; Park, H.J.; Kim, H.M.; Choi, J.H.; Lee, K.T. Tormentic acid, a triterpenoid saponin, isolated from Rosa rugosa, inhibited LPS-induced iNOS, COX-2, and TNF-α expression through inactivation of the nuclear factor-κb pathway in RAW 264.7 macrophages. Int. Immunopharmacol., 2011, 11(4), 504-510.
[http://dx.doi.org/10.1016/j.intimp.2011.01.002] [PMID: 21237302]
[55]
Ramírez-Cisneros, M.A.; Rios, M.Y.; Aguilar-Guadarrama, A.B.; Rao, P.P.; Aburto-Amar, R.; Rodríguez-López, V. In vitro COX-1 and COX-2 enzyme inhibitory activities of iridoids from Penstemon barbatus, Castilleja tenuiflora, Cresentia alata and Vitex mollis. Bioorg. Med. Chem. Lett., 2015, 25(20), 4505-4508.
[http://dx.doi.org/10.1016/j.bmcl.2015.08.075] [PMID: 26351040]
[56]
Ma, J.; Dey, M.; Yang, H.; Poulev, A.; Pouleva, R.; Dorn, R.; Lipsky, P.E.; Kennelly, E.J.; Raskin, I. Anti-inflammatory and immunosuppressive compounds from Tripterygium wilfordii. Phytochemistry, 2007, 68(8), 1172-1178.
[http://dx.doi.org/10.1016/j.phytochem.2007.02.021] [PMID: 17399748]
[57]
Ortiz, M.I.; Fernández-Martínez, E.; Soria-Jasso, L.E.; Lucas-Gómez, I.; Villagómez-Ibarra, R.; González-García, M.P.; Castañeda-Hernández, G.; Salinas-Caballero, M. Isolation, identification and molecular docking as cyclooxygenase (COX) inhibitors of the main constituents of Matricaria chamomilla L. extract and its synergistic interaction with diclofenac on nociception and gastric damage in rats. Biomed. Pharmacother., 2016, 78, 248-256.
[http://dx.doi.org/10.1016/j.biopha.2016.01.029] [PMID: 26898449]
[58]
Heo, S.J.; Yoon, W.J.; Kim, K.N.; Oh, C.; Choi, Y.U.; Yoon, K.T.; Kang, D.H.; Qian, Z.J.; Choi, I.W.; Jung, W.K. Anti-inflammatory effect of fucoxanthin derivatives isolated from Sargassum siliquastrum in lipopolysaccharide-stimulated RAW 264.7 macrophage. Food Chem. Toxicol., 2012, 50(9), 3336-3342.
[http://dx.doi.org/10.1016/j.fct.2012.06.025] [PMID: 22735499]
[59]
Yang, H.J.; Youn, H.; Seong, K.M.; Yun, Y.J.; Kim, W.; Kim, Y.H.; Lee, J.Y.; Kim, C.S.; Jin, Y.W.; Youn, B. Psoralidin, a dual inhibitor of COX-2 and 5-LOX, regulates ionizing radiation (IR)-induced pulmonary inflammation. Biochem. Pharmacol., 2011, 82(5), 524-534.
[http://dx.doi.org/10.1016/j.bcp.2011.05.027] [PMID: 21669192]
[60]
Jung, S.H.; Kim, S.J.; Jun, B.G.; Lee, K.T.; Hong, S.P.; Oh, M.S.; Jang, D.S.; Choi, J.H. α-Cyperone, isolated from the rhizomes of Cyperus rotundus, inhibits LPS-induced COX-2 expression and PGE2 production through the negative regulation of NFκB signalling in RAW 264.7 cells. J. Ethnopharmacol., 2013, 147(1), 208-214.
[http://dx.doi.org/10.1016/j.jep.2013.02.034] [PMID: 23500883]
[61]
Tambewagh, U.U.; Kandhare, A.D.; Honmore, V.S.; Kadam, P.P.; Khedkar, V.M.; Bodhankar, S.L.; Rojatkar, S.R.; Rojatkar, S.R. Anti-inflammatory and antioxidant potential of Guaianolide isolated from Cyathocline purpurea: role of COX-2 inhibition. Int. Immunopharmacol., 2017, 52, 110-118.
[http://dx.doi.org/10.1016/j.intimp.2017.09.001] [PMID: 28888779]
[62]
Chow, Y.L.; Lee, K.H.; Vidyadaran, S.; Lajis, N.H.; Akhtar, M.N.; Israf, D.A.; Syahida, A. Cardamonin from Alpinia rafflesiana inhibits inflammatory responses in IFN-γ/LPS-stimulated BV2 microglia via NF-κB signalling pathway. Int. Immunopharmacol., 2012, 12(4), 657-665.
[http://dx.doi.org/10.1016/j.intimp.2012.01.009] [PMID: 22306767]
[63]
Israf, D.A.; Khaizurin, T.A.; Syahida, A.; Lajis, N.H.; Khozirah, S. Cardamonin inhibits COX and iNOS expression via inhibition of p65NF-kappaB nuclear translocation and Ikappa-B phosphorylation in RAW 264.7 macrophage cells. Mol. Immunol., 2007, 44(5), 673-679.
[http://dx.doi.org/10.1016/j.molimm.2006.04.025] [PMID: 16777230]
[64]
Kwon, H.S.; Park, J.H.; Kim, D.H.; Kim, Y.H.; Park, J.H.Y.; Shin, H.K.; Kim, J.K. Licochalcone A isolated from licorice suppresses lipopolysaccharide-stimulated inflammatory reactions in RAW264.7 cells and endotoxin shock in mice. J. Mol. Med. (Berl.), 2008, 86(11), 1287-1295.
[http://dx.doi.org/10.1007/s00109-008-0395-2] [PMID: 18825356]
[65]
Kim, J.Y.; Park, S.J.; Yun, K.J.; Cho, Y.W.; Park, H.J.; Lee, K.T. Isoliquiritigenin isolated from the roots of Glycyrrhiza uralensis inhibits LPS-induced iNOS and COX-2 expression via the attenuation of NF-kappaB in RAW 264.7 macrophages. Eur. J. Pharmacol., 2008, 584(1), 175-184.
[http://dx.doi.org/10.1016/j.ejphar.2008.01.032] [PMID: 18295200]
[66]
Huang, W.C.; Wu, S.J.; Tu, R.S.; Lai, Y.R.; Liou, C.J. Phloretin inhibits interleukin-1β-induced COX-2 and ICAM-1 expression through inhibition of MAPK, Akt, and NF-κB signaling in human lung epithelial cells. Food Funct., 2015, 6(6), 1960-1967.
[http://dx.doi.org/10.1039/C5FO00149H] [PMID: 25996641]
[67]
Kang, S.R.; Park, K.I.; Park, H.S.; Lee, D.H.; Kim, J.A.; Nagappan, A.; Kim, E.H.; Lee, W.S.; Shin, S.C.; Park, M.K.; Han, D.Y.; Kima, G.S. Anti-inflammatory effect of flavonoids isolated from Korea Citrus aurantium L. on lipopolysaccharide-induced mouse macrophage RAW 264.7 cells by blocking of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signalling pathways. Food Chem., 2011, 129(4), 1721-1728.
[http://dx.doi.org/10.1016/j.foodchem.2011.06.039]
[68]
Chao, C.L.; Weng, C.S.; Chang, N.C.; Lin, J.S.; Kao, S.T.; Ho, F.M. Naringenin more effectively inhibits inducible nitric oxide synthase and cyclooxygenase-2 expression in macrophages than in microglia. Nutr. Res., 2010, 30(12), 858-864.
[http://dx.doi.org/10.1016/j.nutres.2010.10.011] [PMID: 21147369]
[69]
Farombi, E.O.; Shrotriya, S.; Surh, Y.J. Kolaviron inhibits dimethyl nitrosamine-induced liver injury by suppressing COX-2 and iNOS expression via NF-kappaB and AP-1. Life Sci., 2009, 84(5-6), 149-155.
[http://dx.doi.org/10.1016/j.lfs.2008.11.012] [PMID: 19081081]
[70]
Shin, J.S.; Park, Y.M.; Choi, J.H.; Park, H.J.; Shin, M.C.; Lee, Y.S.; Lee, K.T. Sulfuretin isolated from heartwood of Rhus verniciflua inhibits LPS-induced inducible nitric oxide synthase, cyclooxygenase-2, and pro-inflammatory cytokines expression via the down-regulation of NF-kappaB in RAW 264.7 murine macrophage cells. Int. Immunopharmacol., 2010, 10(8), 943-950.
[http://dx.doi.org/10.1016/j.intimp.2010.05.007] [PMID: 20546946]
[71]
Kong, W.; Hooper, K.M.; Ganea, D. The natural dual cyclooxygenase and 5-lipoxygenase inhibitor flavocoxid is protective in EAE through effects on Th1/Th17 differentiation and macrophage/microglia activation. Brain Behav. Immun., 2016, 53, 59-71.
[http://dx.doi.org/10.1016/j.bbi.2015.11.002] [PMID: 26541818]
[72]
Chakraborty, P.; Saraswat, G.; Kabir, S.N. α-Dihydroxychalcone-glycoside (α-DHC) isolated from the heartwood of Pterocarpus marsupium inhibits LPS induced MAPK activation and up regulates HO-1 expression in murine RAW 264.7 macrophage. Toxicol. Appl. Pharmacol., 2014, 277(1), 95-107.
[http://dx.doi.org/10.1016/j.taap.2014.03.011] [PMID: 24675710]
[73]
Fang, S.C.; Hsu, C.L.; Yen, G.C. Anti-inflammatory effects of phenolic compounds isolated from the fruits of Artocarpus heterophyllus. J. Agric. Food Chem., 2008, 56(12), 4463-4468.
[http://dx.doi.org/10.1021/jf800444g] [PMID: 18500810]
[74]
Pendota, S.; Ndhlala, A.R.; Aremu, A.O.; Aderogba, M.A.; Van Staden, J. Anti-inflammatory, antioxidant and in silico studies of Buddleja salviifolia (L). Lam leaf constituents. S. Afr. J. Bot., 2014, 93, 79-85.
[http://dx.doi.org/10.1016/j.sajb.2014.03.012]
[75]
Waller, C.P.; Thumser, A.E.; Langat, M.K.; Crouch, N.R.; Mulholland, D.A. COX-2 inhibitory activity of homoisoflavanones and xanthones from the bulbs of the Southern African Ledebouria socialis and Ledebouria ovatifolia (Hyacinthaceae: Hyacinthoideae). Phytochemistry, 2013, 95, 284-290.
[http://dx.doi.org/10.1016/j.phytochem.2013.06.024] [PMID: 23859260]
[76]
Jachak, S.M.; Gautam, R.; Selvam, C.; Madhan, H.; Srivastava, A.; Khan, T. Anti-inflammatory, cyclooxygenase inhibitory and antioxidant activities of standardized extracts of Tridax procumbens L. fitoterapia, 2011, 82(2), 173-177.
[http://dx.doi.org/10.1016/j.fitote.2010.08.016] [PMID: 20804828]
[77]
Choi, S.E.; Park, K.H.; Han, B.H.; Jeong, M.S.; Seo, S.J.; Lee, D.I.; Joo, S.S.; Lee, M.W. Inhibition of inducible nitric oxide synthase and cyclooxygenase-2 expression by phenolic compounds from roots of Rhododendron mucronulatum. Phytother. Res., 2011, 25(9), 1301-1305.
[http://dx.doi.org/10.1002/ptr.3376] [PMID: 21312305]
[78]
Bairwa, K.; Singh, I.N.; Roy, S.K.; Grover, J.; Srivastava, A.; Jachak, S.M. Rotenoids from Boerhaavia diffusa as potential anti-inflammatory agents. J. Nat. Prod., 2013, 76(8), 1393-1398.
[http://dx.doi.org/10.1021/np300899w] [PMID: 23914900]
[79]
Bairwa, K.; Singh, I.N.; Roy, S.K.; Grover, J.; Srivastav, A.; Jachak, S.M. Correction to rotenoids from Boerhaavia diffusa as potential anti-inflammatory agents. J. Nat. Prod., 2013, 76(12), 2364.
[http://dx.doi.org/10.1021/np4009464]
[80]
Honmore, V.S.; Kandhare, A.D.; Kadam, P.P.; Khedkar, V.M.; Sarkar, D.; Bodhankar, S.L.; Zanwar, A.A.; Rojatkar, S.R.; Natu, A.D. Isolates of Alpinia officinarum Hance as COX-2 inhibitors: evidence from anti-inflammatory, antioxidant and molecular docking studies. Int. Immunopharmacol., 2016, 33, 8-17.
[http://dx.doi.org/10.1016/j.intimp.2016.01.024] [PMID: 26849772]
[81]
Gautam, R.; Srivastava, A.; Jachak, S.M.; Saklani, A. Anti-inflammatory, cyclooxygenase (COX)-2, COX-1 inhibitory and antioxidant effects of Dysophylla stellata Benth. Fitoterapia, 2010, 81(1), 45-49.
[http://dx.doi.org/10.1016/j.fitote.2009.07.004] [PMID: 19632309]
[82]
Gautam, R.; Jachak, S.M.; Kumar, V.; Mohan, C.G. Synthesis, biological evaluation and molecular docking studies of stellatin derivatives as cyclooxygenase (COX-1, COX-2) inhibitors and anti-inflammatory agents. Bioorg. Med. Chem. Lett., 2011, 21(6), 1612-1616.
[http://dx.doi.org/10.1016/j.bmcl.2011.01.116] [PMID: 21345672]
[83]
Grover, J.; Jachak, S.M. Coumarins as privileged scaffold for anti-inflammatory drug development. RSC Advances, 2015, 5(49), 38892-38905.
[http://dx.doi.org/10.1039/C5RA05643H]
[84]
Nakamura, T.; Kodama, N.; Arai, Y.; Kumamoto, T.; Higuchi, Y.; Chaichantipyuth, C.; Ishikawa, T.; Ueno, K.; Yano, S. Inhibitory effect of oxycoumarins isolated from the Thai medicinal plant Clausena guillauminii on the inflammation mediators, iNOS, TNF-α, and COX-2 expression in mouse macrophage RAW 264.7. J. Nat. Med., 2009, 63(1), 21-27.
[http://dx.doi.org/10.1007/s11418-008-0277-5] [PMID: 18636311]
[85]
Kang, K.H.; Kong, C.S.; Seo, Y.; Kim, M.M.; Kim, S.K. Anti-inflammatory effect of coumarins isolated from Corydalis heterocarpa in HT-29 human colon carcinoma cells. Food Chem. Toxicol., 2009, 47(8), 2129-2134.
[http://dx.doi.org/10.1016/j.fct.2009.05.036] [PMID: 19500635]
[86]
Ishita, I.J.; Islam, M.N.; Kim, Y.S.; Choi, R.J.; Sohn, H.S.; Jung, H.A.; Choi, J.S. Coumarins from Angelica decursiva inhibit lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells. Arch. Pharm. Res., 2016, 39(1), 115-126.
[http://dx.doi.org/10.1007/s12272-015-0668-6] [PMID: 26474585]
[87]
Tong, L.; Chen, T.; Chen, Z.; Zhang, P.; Pi, H.; Ruan, H.; Wu, J. Anti-inflammatory activity of omphalocarpin isolated from radix toddaliae asiaticae. J. Ethnopharmacol., 2014, 155(3), 1553-1560.
[http://dx.doi.org/10.1016/j.jep.2014.07.055] [PMID: 25102246]
[88]
Zhou, H.Y.; Shin, E.M.; Guo, L.Y.; Youn, U.J.; Bae, K.; Kang, S.S.; Zou, L.B.; Kim, Y.S. Anti-inflammatory activity of 4-methoxyhonokiol is a function of the inhibition of iNOS and COX-2 expression in RAW 264.7 macrophages via NF-kappaB, JNK and p38 MAPK inactivation. Eur. J. Pharmacol., 2008, 586(1-3), 340-349.
[http://dx.doi.org/10.1016/j.ejphar.2008.02.044] [PMID: 18378223]
[89]
Kim, J.Y.; Lim, H.J.; Lee, Y.; Kim, J.S.; Kim, D.H.; Lee, H.J.; Kim, H.D.; Jeon, R.; Ryu, J.H. In vitro anti-inflammatory activity of lignans isolated from Magnolia fargesii. Bioorg. Med. Chem. Lett., 2009, 19(3), 937-940.
[http://dx.doi.org/10.1016/j.bmcl.2008.11.103] [PMID: 19110419]
[90]
Lim, H.; Lee, J.G.; Lee, S.H.; Kim, Y.S.; Kim, H.P. Anti-inflammatory activity of phylligenin, a lignan from the fruits of Forsythia koreana, and its cellular mechanism of action. J. Ethnopharmacol., 2008, 118(1), 113-117.
[http://dx.doi.org/10.1016/j.jep.2008.03.016] [PMID: 18467047]
[91]
Guo, L.Y.; Hung, T.M.; Bae, K.H.; Shin, E.M.; Zhou, H.Y.; Hong, Y.N.; Kang, S.S.; Kim, H.P.; Kim, Y.S. Anti-inflammatory effects of schisandrin isolated from the fruit of Schisandra chinensis Baill. Eur. J. Pharmacol., 2008, 591(1-3), 293-299.
[http://dx.doi.org/10.1016/j.ejphar.2008.06.074] [PMID: 18625216]
[92]
Gautam, R.; Karkhile, K.V.; Bhutani, K.K.; Jachak, S.M. Anti-inflammatory, cyclooxygenase (COX)-2, COX-1 inhibitory, and free radical scavenging effects of Rumex nepalensis. Planta Med., 2010, 76(14), 1564-1569.
[http://dx.doi.org/10.1055/s-0030-1249779] [PMID: 20379952]
[93]
Grover, J.; Kumar, V.; Singh, V.; Bairwa, K.; Sobhia, M.E.; Jachak, S.M. Synthesis, biological evaluation, molecular docking and theoretical evaluation of ADMET properties of nepodin and chrysophanol derivatives as potential cyclooxygenase (COX-1, COX-2) inhibitors. Eur. J. Med. Chem., 2014, 80, 47-56.
[http://dx.doi.org/10.1016/j.ejmech.2014.04.033] [PMID: 24763362]
[94]
Handler, N.; Jaeger, W.; Puschacher, H.; Leisser, K.; Erker, T. Synthesis of novel curcumin analogues and their evaluation as selective cyclooxygenase-1 (COX-1) inhibitors. Chem. Pharm. Bull. (Tokyo), 2007, 55(1), 64-71.
[http://dx.doi.org/10.1248/cpb.55.64] [PMID: 17202703]
[95]
Ahmed, M.; Qadir, M.A.; Hameed, A.; Imran, M.; Muddassar, M. Screening of curcumin-derived isoxazole, pyrazoles, and pyrimidines for their anti-inflammatory, antinociceptive, and cyclooxygenase-2 inhibition. Chem. Biol. Drug Des., 2018, 91(1), 338-343.
[http://dx.doi.org/10.1111/cbdd.13076] [PMID: 28741789]
[96]
Bandgar, B.P.; Hote, B.S.; Jalde, S.S.; Gacche, R.N. Synthesis and biological evaluation of novel curcumin analogues as anti-inflammatory, anti-cancer and anti-oxidant agents. Med. Chem. Res., 2012, 21(10), 3006-3014.
[http://dx.doi.org/10.1007/s00044-011-9834-7]
[97]
Ahmad, W.; Kumolosasi, E.; Jantan, I.; Bukhari, S.N.; Jasamai, M. Effects of novel diarylpentanoid analogues of curcumin on secretory phospholipase A2, cyclooxygenases, lipo-oxygenase, and microsomal prostaglandin E synthase-1. Chem. Biol. Drug Des., 2014, 83(6), 670-681.
[http://dx.doi.org/10.1111/cbdd.12280] [PMID: 24406103]
[98]
Yang, M.H.; Yoon, K.D.; Chin, Y.W.; Park, J.H.; Kim, J. Phenolic compounds with radical scavenging and cyclooxygenase-2 (COX-2) inhibitory activities from Dioscorea opposita. Bioorg. Med. Chem., 2009, 17(7), 2689-2694.
[http://dx.doi.org/10.1016/j.bmc.2009.02.057] [PMID: 19303782]
[99]
Lee, C.J.; Chen, L.G.; Liang, W.L.; Wang, C.C. Anti-inflammatory effects of Punica granatum Linne in vitro and in vivo. Food Chem., 2010, 118(2), 315-322.
[http://dx.doi.org/10.1016/j.foodchem.2009.04.123]
[100]
Reddy, D.B.; Reddy, T.C.M.; Jyotsna, G.; Sharan, S.; Priya, N.; Lakshmipathi, V.; Reddanna, P. Chebulagic acid, a COX-LOX dual inhibitor isolated from the fruits of Terminalia chebula Retz., induces apoptosis in COLO-205 cell line. J. Ethnopharmacol., 2009, 124(3), 506-512.
[http://dx.doi.org/10.1016/j.jep.2009.05.022] [PMID: 19481594]
[101]
Zhang, Y.; Shi, S.; Zhao, M.; Chai, X.; Tu, P. Coreosides A-D, C14-polyacetylene glycosides from the capitula of Coreopsis tinctoria and its anti-inflammatory activity against COX-2. Fitoterapia, 2013, 87, 93-97.
[http://dx.doi.org/10.1016/j.fitote.2013.03.024] [PMID: 23562631]
[102]
Hwang, S.W.; Lee, J.; Shin, J.S.; Lee, J.Y.; Lee, K.T.; Jang, D.S. Inhibitory effects of phenylpropanoids isolated from the bark of Ailanthus altissima on COX-2 activity. Bull. Korean Chem. Soc., 2012, 33(8), 2759-2761.
[http://dx.doi.org/10.5012/bkcs.2012.33.8.2759]
[103]
Wang, J.; Wei, X.; Lu, X.; Xu, F.; Wan, J.; Lin, X.; Zhou, X.; Liao, S.; Yang, B.; Tu, Z.; Liu, Y. Eight new polyketide metabolites from the fungus Pestalotiopsis vaccinii endogenous with the mangrove plant Kandelia candel (L.). Druce. Tetrahedron, 2014, 70(51), 9695-9701.
[http://dx.doi.org/10.1016/j.tet.2014.10.056]
[104]
Ju, Z.; Lin, X.; Lu, X.; Tu, Z.; Wang, J.; Kaliyaperumal, K.; Liu, J.; Tian, Y.; Xu, S.; Liu, Y. Botryoisocoumarin A, a new COX-2 inhibitor from the mangrove Kandelia candel endophytic fungus Botryosphaeria sp. KcF6. J. Antibiot. (Tokyo), 2015, 68(10), 653-656.
[http://dx.doi.org/10.1038/ja.2015.46] [PMID: 25966851]
[105]
Ai, W.; Lin, X.P.; Tu, Z.; Tian, X.P.; Lu, X.; Mangaladoss, F.; Zhong, Z.L.; Liu, Y. Axinelline A, a new COX-2 inhibitor from Streptomyces axinellae SCSIO02208. Nat. Prod. Res., 2014, 28(16), 1219-1224.
[http://dx.doi.org/10.1080/14786419.2014.891204] [PMID: 24666327]
[106]
Lu, Y.; Li, P.J.; Hung, W.Y.; Su, J.H.; Wen, Z.H.; Hsu, C.H.; Dai, C.F.; Chiang, M.Y.; Sheu, J.H. Nardosinane sesquiterpenoids from the Formosan soft coral Lemnalia flava. J. Nat. Prod., 2011, 74(2), 169-174.
[http://dx.doi.org/10.1021/np100541a] [PMID: 21204521]
[107]
Jean, Y.H.; Chen, W.F.; Duh, C.Y.; Huang, S.Y.; Hsu, C.H.; Lin, C.S.; Sung, C.S.; Chen, I.M.; Wen, Z.H. Inducible nitric oxide synthase and cyclooxygenase-2 participate in anti-inflammatory and analgesic effects of the natural marine compound lemnalol from Formosan soft coral Lemnalia cervicorni. Eur. J. Pharmacol., 2008, 578(2-3), 323-331.
[http://dx.doi.org/10.1016/j.ejphar.2007.08.048] [PMID: 17916350]
[108]
Ahmed, A.F.; Hsieh, Y.T.; Wen, Z.H.; Wu, Y.C.; Sheu, J.H. Polyoxygenated sterols from the Formosan soft coral Sinularia gibberosa. J. Nat. Prod., 2006, 69(9), 1275-1279.
[http://dx.doi.org/10.1021/np0601509] [PMID: 16989519]
[109]
Jean, Y.H.; Chen, W.F.; Sung, C.S.; Duh, C.Y.; Huang, S.Y.; Lin, C.S.; Tai, M.H.; Tzeng, S.F.; Wen, Z.H. Capnellene, a natural marine compound derived from soft coral, attenuates chronic constriction injury-induced neuropathic pain in rats. Br. J. Pharmacol., 2009, 158(3), 713-725.
[http://dx.doi.org/10.1111/j.1476-5381.2009.00323.x] [PMID: 19663884]
[110]
Chao, C.H.; Wen, Z.H.; Wu, Y.C.; Yeh, H.C.; Sheu, J.H. Cytotoxic and anti-inflammatory cembranoids from the soft coral Lobophytum crassum. J. Nat. Prod., 2008, 71(11), 1819-1824.
[http://dx.doi.org/10.1021/np8004584] [PMID: 18973388]
[111]
Jung, W.K.; Heo, S.J.; Jeon, Y.J.; Lee, C.M.; Park, Y.M.; Byun, H.G.; Choi, Y.H.; Park, S.G.; Choi, I.W. Inhibitory effects and molecular mechanism of dieckol isolated from marine brown alga on COX-2 and iNOS in microglial cells. J. Agric. Food Chem., 2009, 57(10), 4439-4446.
[http://dx.doi.org/10.1021/jf9003913] [PMID: 19408937]
[112]
Joyner, P.M.; Waters, A.L.; Williams, R.B.; Powell, D.R.; Janakiram, N.B.; Rao, C.V.; Cichewicz, R.H. Briarane diterpenes diminish COX-2 expression in human colon adenocarcinoma cells. J. Nat. Prod., 2011, 74(4), 857-861.
[http://dx.doi.org/10.1021/np100775a] [PMID: 21438584]
[113]
Hsu, F.J.; Chen, B.W.; Wen, Z.H.; Huang, C.Y.; Dai, C.F.; Su, J.H.; Wu, Y.C.; Sheu, J.H. Klymollins A-H, bioactive eunicellin-based diterpenoids from the formosan soft coral Klyxum molle. J. Nat. Prod., 2011, 74(11), 2467-2471.
[http://dx.doi.org/10.1021/np200589n] [PMID: 22004052]
[114]
Wu, S.L.; Su, J.H.; Wen, Z.H.; Hsu, C.H.; Chen, B.W.; Dai, C.F.; Kuo, Y.H.; Sheu, J.H. Simplexins A-I, eunicellin-based diterpenoids from the soft coral Klyxum simplex. J. Nat. Prod., 2009, 72(6), 994-1000.
[http://dx.doi.org/10.1021/np900064a] [PMID: 19391605]
[115]
Qin, C.; Lin, X.; Lu, X.; Wan, J.; Zhou, X.; Liao, S.; Tu, Z.; Xu, S.; Liu, Y. Sesquiterpenoids and xanthones derivatives produced by sponge-derived fungus Stachybotry sp. HH1 ZSDS1F1-2. J. Antibiot. (Tokyo), 2015, 68(2), 121-125.
[http://dx.doi.org/10.1038/ja.2014.97] [PMID: 25118104]
[116]
Hassan, H.M.; Boonlarppradab, C.; Fenical, W. Actinoquinolines A and B, anti-inflammatory quinoline alkaloids from a marine-derived Streptomyces sp., strain CNP975. J. Antibiot. (Tokyo), 2016, 69(7), 511-514.
[http://dx.doi.org/10.1038/ja.2016.56] [PMID: 27220408]
[117]
Makkar, F.; Chakraborty, K. First report of dual cyclooxygenase-2 and 5-lipoxygenase inhibitory halogen derivatives from the thallus of intertidal seaweed Kappaphycus alvarezii. Med. Chem. Res., 2018, 27(10), 2331-2340.
[http://dx.doi.org/10.1007/s00044-018-2239-0]

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