Molecular basis of the anti-inflammatory effects of terpenoids

Inflammation and Allergy - Drug Targets

Volumn 8, Issue 1, 2009, Pages 28-39

  de las Heras, B ^a   Hortelano, Sonsoles ^b  

^a UNIVERSIDAD COMPLUTENSE DE MADRID   (Spain)

^b CENTRO NACIONAL DE INVESTIGACIONES CARDIOVASCULARES CNIC   (Spain)

Author keywords

Inflammation; Innate immunity; NF B; Terpenoids

Indexed keywords

ACANTHOIC ACID; ANDALUSOL; ANDROGRAPHOLIDE; ANTIINFLAMMATORY AGENT; CARNOSIC ACID; CARNOSOL; CYCLOAMPHILECTENE 2; DITERPENOID; ENT KAURANE DITERPENOID; EXCISANIN A; FOLIOL; HISPANOLONE DERIVATIVE; HYPOESTOXIDE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INFLEXINOL; KAMABECETAL; KAMEBAKAURIN; KAMEBANIN; KAURANE DERIVATIVE; LINEAROL; ORIDONIN; PEPLUANONE; PINUSOLIDE; PLANT MEDICINAL PRODUCT; PONICIDIN; SIEGESKAUROLIC ACID; TANSHINONE IIA; TERPENOID; TRIPTOLIDE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ANTIINFLAMMATORY ACTIVITY; APOPTOSIS; BIOLOGICAL ACTIVITY; BIOTECHNOLOGY; CELL ADHESION; CELL PROLIFERATION; CELLULAR STRESS RESPONSE; CHRONIC INFLAMMATION; DRUG MECHANISM; GENE EXPRESSION REGULATION; HUMAN; HUMORAL IMMUNITY; IMMUNOREGULATION; INFLAMMATION; INNATE IMMUNITY; MARINE SPECIES; NONHUMAN; OTITIS; PAIN; PAW EDEMA; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION;

ANIMALS; ANTI-INFLAMMATORY AGENTS; AUTOIMMUNE DISEASES; DITERPENES; DRUG THERAPY; HUMANS; HYPERSENSITIVITY; IMMUNOSUPPRESSION; MEDICINE, TRADITIONAL; NEOPLASMS; NF-KAPPA B; SIGNAL TRANSDUCTION; TERPENES; TRANSCRIPTIONAL ACTIVATION; TUMOR NECROSIS FACTOR-ALPHA;

EID: 70349515074     PISSN: 18715281     EISSN: None     Source Type: Journal    
DOI: 10.2174/187152809787582534     Document Type: Review

References (83)

1. Serhan, C.N.; Savill, J. Resolution of inflammation: the beginning programs the end. Nat. Immunol., 2005, 6, 1191-1197.
2. Serhan, C.N.; Clish, C.B.; Brannon, J.; Colgan, S.P.; Chiang, N.; Gronert, K. Novel functional sets of lipid-derived mediators with antiinflammatory actions generated from omega-3 fatty acids via cyclooxygenase 2-nonsteroidal antiinflammatory drugs and transcellular processing. J. Exp. Med., 2000, 192, 197-1204.
3. Serhan, C.N.; Hong,.; Gronert, K.; Colgan, S.P.; Devchand, P.R.; Mirick, G.; Moussignac, R.L. Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals. J. Exp. Med., 2002, 196, 1025-1037.
4. Serhan, C.N.; Chiang, N.; Van Dyke, T.E. Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat. Rev. Immunol., 2008, 8, 349-361.
5. Mercurio, F.; Manning, A.M. Multiple signals converging on NF-kappaB. Curr. Opin. Cell Biol., 1999, 11, 226-232.
6. Tickle, C. Worlds in common through NF-kappaB. Nature, 1998, 392, 547-549.
7. Hayden, M.S.; Ghosh, S. Signaling to NF-kappaB. Genes Dev., 2004, 18, 2195-2224.
8. Bonizzi, G.; Karin, M. The two NF-kappaB activation pathways and their role in innate and adaptive immunity. Trends Immunol., 2004, 25, 280-288.
9. Gerondakis, S.; Grossmann, M.; Nakamura, Y.; Pohl, T.; Grumont, R. Genetic approaches in mice to understand Rel/NF-kappaB and IkappaB function: transgenics and knockouts. Oncogene, 1999, 18, 6888-6895.
10. Pasparakis, M.; Luedde, T.; Schmidt-Supprian, M. Dissection of the NF-kappaB signalling cascade in transgenic and knockout mice. Cell Death Differ., 2006, 13, 861-872.
11. Pahl, H.L. Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene, 1999, 18, 6853-6866.
12. Baeuerle, P.A.; Baichwal, V.R. NF-kappa B as a frequent target for immunosuppressive and anti-inflammatory molecules. Adv. Immunol., 1997, 65, 111-137.
13. Baeuerle, P.A.; Henkel, T. Function and activation of NF-kappa B in the immune system. Annu. Rev. Immunol., 1994, 12, 141-179.
14. Siebenlist, U.; Franzoso, G.; Brown, K. Structure, regulation and function of NF-kappa B. Annu. Rev. Cell Biol., 1994, 10, 405-455.
15. Ghosh, S.; Karin, M. Missing pieces in the NF-kappaB puzzle. Cell, 2002, 109 Suppl, S81-S96.
16. Keutgens, A.; Robert, I.; Viatour, P.; Chariot, A. Deregulated NF-kappaB activity in haematological malignancies. Biochem. Pharmacol., 2006, 72, 1069-1080.
17. Dejardin, E.; Droin, N.M.; Delhase, M.; Haas, E.; Cao, Y.; Makris, C.; Li, Z.W.; Karin, M.; Ware, C.F.; Green, D.R. The lymphotoxin-beta receptor induces different patterns of gene expression via two NF-kappaB pathways. Immunity, 2002, 17, 525-535.
18. Claudio, E.; Brown, K.; Park, S.; Wang, H.; Siebenlist, U. BAFF-induced NEMO-independent processing of NF-kappa B2 in maturing B cells. Nat. Immunol., 2002, 3, 958-965.
19. Coope, H.J.; Atkinson, P.G.; Huhse, B.; Belich, M.; Janzen, J.; Holman, M.J.; Klaus, G.G.; Johnston, L.H.; Ley, S.C. CD40 regulates the processing of NF-kappaB2 p100 to p52. EMBO J., 2002, 21, 5375-5385.
20. Perkins, N.D. Post-translational modifications regulating the activity and function of the nuclear factor kappa B pathway. Oncogene, 2006, 25, 6717-6730.
21. Balunas, M.J.; Kinghorn, A.D. Drug discovery from medicinal plants. Life Sci., 2005, 78, 431-441.
22. Newman, D.J.; Cragg, G.M. Natural products as sources of new drugs over the last 25 years. J. Nat. Prod., 2007, 70, 461-477.
23. Bouvier, F.; Rahier, A.; Camara, B. Biogenesis, molecular regulation and function of plant isoprenoids. Prog. Lipid Res., 2005, 44, 357-429.
24. Bohlmann, J.; Keeling, C.I. Terpenoid biomaterials. Plant J., 2008, 54, 656-669.
25. Keeling, C.I.; Bohlmann, J. Genes, enzymes and chemicals of terpenoid diversity in the constitutive and induced defence of conifers against insects and pathogens. New Phytol., 2006, 170, 657-675.
26. Tholl, D. Terpene synthases and the regulation, diversity and biological roles of terpene metabolism. Curr. Opin. Plant Biol., 2006, 9, 297-304.
27. De las Heras, B.; Rodriguez, B.; Bosca, L.; Villar, A.M. Terpenoids: sources, structure elucidation and therapeutic potential in inflammation. Curr. Top. Med. Chem., 2003, 3, 171-185.
28. Singh, M.; Pal, M.; Sharma, R.P. Biological activity of the labdane diterpenes. Planta Med., 1999, 65, 2-8.
29. Kopp, E.; Ghosh, S. Inhibition of NF-kappa B by sodium salicylate and aspirin. Science, 1994, 265, 956-959.
30. Bremner, P.; Heinrich, M. Natural products as targeted modulators of the nuclear factor-kappaB pathway. J. Pharm. Pharmacol., 2002, 54, 453-472.
31. Karin, M.; Yamamoto, Y.; Wang, Q.M. The IKK NF-kappa B system: a treasure trove for drug development. Nat. Rev. Drug Discov., 2004, 3, 17-26.
32. Lyss, G.; Knorre, A.; Schmidt, T.J.; Pahl, H.L.; Merfort, I. The anti-inflammatory sesquiterpene lactone helenalin inhibits the transcription factor NF-kappaB by directly targeting p65. J. Biol. Chem., 1998, 273, 33508-33516.
33. Natarajan, K.; Singh, S.; Burke, T.R., Jr.; Grunberger, D.; Aggarwal, B.B. Caffeic acid phenethyl ester is a potent and specific inhibitor of activation of nuclear transcription factor NF-kappa B. Proc. Natl. Acad. Sci. US A., 1996, 93, 9090-9095.
34. D'acquisto, F.; Lanzotti, V.; Carnuccio, R. Cyclolinteinone, a sesterterpene from sponge Cacospongia linteiformis, prevents inducible nitric oxide synthase and inducible cyclo-oxygenase protein expression by blocking nuclear factor-kappaB activation in J774 macrophages. Biochem. J., 2000, 346, Pt 3, 793-798.
35. Leung, C.H.; Grill, S.P.; Lam, W.; Han, Q.B.; Sun, H.D.; Cheng, Y.C. Novel mechanism of inhibition of nuclear factor-kappa B DNA-binding activity by diterpenoids isolated from Isodon rubescens. Mol. Pharmacol., 2005, 68, 286-297.
36. Straus, D.S.; Pascual, G.; Li, M.; Welch, J.S.; Ricote, M.; Hsiang, C.H.; Sengchanthalangsy, L.L.; Ghosh, G.; Glass, C.K. 15-deoxy-delta 12,14-prostaglandin J2 inhibits multiple steps in the NF-kappa B signaling pathway. Proc. Natl. Acad. Sci. USA., 2000, 97, 4844-4849.
37. Scheinman, R.I.; Cogswell, P.C.; Lofquist, A.K.; Baldwin, A.S., Jr. Role of transcriptional activation of I kappa B alpha in mediation of immunosuppression by glucocorticoids. Science, 1995, 270, 283-286.
38. Adams, J.; Palombella, V.J.; Elliott, P.J. Proteasome inhibition: a new strategy in cancer treatment. Invest. New Drugs, 2000, 18, 109-121.
39. Ogino, S.; Tsuruma, K.; Uehara, T.; Nomura, Y. Herbimycin A abrogates nuclear factor-kappaB activation by interacting preferentially with the IkappaB kinase beta subunit. Mol. Pharmacol., 2004, 65, 1344-1351.
40. Garcia-Pineres, A.J.; Lindenmeyer, M.T.; Merfort, I. Role of cysteine residues of p65/NF-kappaB on the inhibition by the sesquiterpene lactone parthenolide and N-ethyl maleimide, and on its trans-activating potential. Life Sci., 2004, 75, 841-856.
41. Lee, J.H.; Koo, T.H.; Hwang, B.Y.; Lee, J.J. Kaurane diterpene, kamebakaurin, inhibits NF-kappa B by directly targeting the DNA-binding activity of p50 and blocks the expression of antiapoptotic NF-kappa B target genes. J. Biol. Chem., 2002, 277, 18411-18420.
42. Giron, N.; Traves, P.G.; Rodriguez, B.; Lopez-Fontal, R.; Bosca, L.; Hortelano, S.; de las Heras, B. Suppression of inflammatory responses by labdane-type diterpenoids. Toxicol. Appl. Pharmacol., 2008, 228, 179-189.
43. Hanson, J.R. Diterpenoids. Nat. Prod. Rep., 2007, 24, 1332-1341.
44. Chinou, I. Labdanes of natural origin-biological activities (1981-2004). Curr. Med. Chem., 2005, 12, 1295-1317.
45. Navarro, A.; De las Heras, B.; Villar, A.M. Andalusol, a diterpenoid with anti-inflammatory activity from Siderits foetens Clemen. Z. Naturforsch. [C.]., 1997, 52, 844-849.
46. De las Heras, B.; Navarro, A.; Diaz-Guerra, M.J.; Bermejo, P.; Castrillo, A.; Bosca, L.; Villar, A. Inhibition of NOS-2 expression in macrophages through the inactivation of NF-kappaB by andalusol. Br. J. Pharmacol., 1999, 128, 605-612.
47. Qin, L.H.; Kong, L.; Shi, G.J.; Wang, Z.T.; Ge, B.X. Andrographolide inhibits the production of TNF-alpha and interleukin-12 in lipopolysaccharide-stimulated macrophages: role of mitogen-activated protein kinases. Biol. Pharm. Bull., 2006, 29, 220-224.
48. Xia, Y.F.; Ye, B.Q.; Li, Y.D.; Wang, J.G.; He, X.J.; Lin, X.; Yao, X.; Ma, D.; Slungaard, A.; Hebbel, R.P.; Key, N.S.; Geng, J.G. Andrographolide attenuates inflammation by inhibition of NF-kappa B activation through covalent modification of reduced cysteine 62 of p50. J. Immunol., 2004, 173, 4207-4217.
49. Jiang, C.G.; Li, J.B.; Liu, F.R.; Wu, T.; Yu, M.; Xu, H.M. Andrographolide inhibits the adhesion of gastric cancer cells to endothelial cells by blocking E-selectin expression. Anticancer Res., 2007, 27, 2439-2447.
50. Choi, Y.; Moon, A.; Kim, Y.C. A pinusolide derivative, 15-methoxypinusolidic acid from Biota orientalis inhibits inducible nitric oxide synthase in microglial cells: implication for a potential anti-inflammatory effect. Int. Immunopharmacol., 2008, 8, 548-555.
51. Ojo-Amaize, E.A.; Kapahi, P.; Kakkanaiah, V.N.; Takahashi, T.; Shalom-Barak, T.; Cottam, H.B.; Adesomoju, A.A.; Nchekwube, E.J.; Oyemade, O.A.; Karin, M.; Okogun, J.I. Hypoestoxide, a novel anti-inflammatory natural diterpene, inhibits the activity of IkappaB kinase. Cell Immunol., 2001, 209, 149-157.
52. Ojo-Amaize, E.A.; Nchekwube, E.J.; Cottam, H.B.; Bai, R.; Verdier-Pinard, P.; Kakkanaiah, V.N.; Varner, J.A.; Leoni, L.; Okogun, J.I.; Adesomoju, A.A.; Oyemade, O.A.; Hamel, E. Hypoestoxide, a natural nonmutagenic diterpenoid with antiangiogenic and antitumor activity: possible mechanisms of action. Cancer Res., 2002, 62, 4007-4014.
53. Jang, S.I.; Kim, H.J.; Kim, Y.J.; Jeong, S.I.; You, Y.O. Tanshinone IIA inhibits LPS-induced NF-kappaB activation in RAW 264.7 cells: possible involvement of the NIK-IKK, ERK1/2, p38 and JNK pathways. Eur. J. Pharmacol., 2006, 542, 1-7.
54. Xu, Y.; Feng, D.; Wang, Y.; Lin, S.; Xu, L. Sodium Tanshinone IIA Sulfonate Protects Mice From ConA-Induced Hepatitis via Inhibiting NF-kappaB and IFN-gamma/STAT1 Pathways. J. Clin. Immunol., 2008.
55. Lam, T.; Ling, T.; Chowdhury, C.; Chao, T.H.; Bahjat, F.R.; Lloyd, G.K.; Moldawer, L.L.; Palladino, M.A.; Theodorakis, E.A.; Theodorakis, E.A. Synthesis of a novel family of diterpenes and their evaluation as anti-inflammatory agents. Bioorg. Med. Chem. Lett., 2003, 13, 3217-3221.
56. Chao, T.H.; Lam, T.; Vong, B.G.; Traves, P.G.; Hortelano, S.; Chowdhury, C.; Bahjat, F.R.; Lloyd, G.K.; Moldawer, L.L.; Bosca, L.; Palladino, M.A.; Theodorakis, E.A. A new family of synthetic diterpenes that regulates cytokine synthesis by inhibiting Ikappa-Balpha phosphorylation. Chembiochem., 2005, 6, 133-144.
57. Traves, P.G.; Hortelano, S.; Zeini, M.; Chao, T.H.; Lam, T.; Neuteboom, S.T.; Theodorakis, E.A.; Palladino, M.A.; Castrillo, A.; Bosca, L. Selective activation of liver X receptors by acanthoic acid-related diterpenes. Mol. Pharmacol., 2007, 71, 1545-1553.
58. Joseph, S.B.; Castrillo, A.; Laffitte, B.A.; Mangelsdorf, D.J.; Tontonoz, P. Reciprocal regulation of inflammation and lipid metabolism by liver X receptors. Nat. Med., 2003, 9, 213-219.
59. Castrillo, A.; Joseph, S.B.; Marathe, C.; Mangelsdorf, D.J.; Tontonoz, P. Liver X receptor-dependent repression of matrix metalloproteinase-9 expression in macrophages. J. Biol. Chem., 2003, 278, 10443-10449.
60. Huang, M.T.; Ho, C.T.; Wang, Z.Y.; Ferraro, T.; Lou, Y.R.; Stauber, K.; Ma, W.; Georgiadis, C.; Laskin, J.D.; Conney, A.H. Inhibition of skin tumorigenesis by rosemary and its constituents carnosol and ursolic acid. Cancer Res., 1994, 54, 701-708.
61. Huang, S.C.; Ho, C.T.; Lin-Shiau, S.Y.; Lin, J.K. Carnosol inhibits the invasion of B16/F10 mouse melanoma cells by suppressing metalloproteinase-9 through down-regulating nuclear factor-kappa B and c-Jun. Biochem. Pharmacol., 2005, 69, 221-232.
62. Lo, A.H.; Liang, Y.C.; Lin-Shiau, S.Y.; Ho, C.T.; Lin, J.K. Carnosol, an antioxidant in rosemary, suppresses inducible nitric oxide synthase through down-regulating nuclear factor-kappaB in mouse macrophages. Carcinogenesis, 2002, 23, 983-991.
63. Garcia, P.A.; de Oliveira, A.B.; Batista, R. Occurrence, biological activities and synthesis of kaurane diterpenes and their glycosides. Molecules, 2007, 12, 455-483.
64. Tudzynski, B. Biosynthesis of gibberellins in Gibberella fujikuroi: biomolecular aspects. Appl. Microbiol. Biotechnol., 1999, 52, 298-310.
65. Yamaguchi, S. Gibberellin metabolism and its regulation. Annu. Rev. Plant Biol., 2008, 59, 225-51.
66. Castrillo, A.; de las Heras, B.; Hortelano, S.; Rodriguez, B.; Villar, A.; Bosca, L. Inhibition of the nuclear factor kappa B (NF-kappa B) pathway by tetracyclic kaurene diterpenes in macrophages. Specific effects on NF-kappa B-inducing kinase activity and on the coordinate activation of ERK and p38 MAPK J. Biol. Chem., 2001, 276, 15854-15860.
67. Park, H.J.; Kim, I.T.; Won, J.H.; Jeong, S.H.; Park, E.Y.; Nam, J.H.; Choi, J.; Lee, K.T. Anti-inflammatory activities of ent-16alphaH,17-hydroxy-kauran-19-oic acid isolated from the roots of Siegesbeckia pubescens are due to the inhibition of iNOS and COX-2 expression in RAW 264.7 macrophages via NF-kappaB inactivation. Eur. J. Pharmacol., 2007, 558, 185-193.
68. Giang, P.M.; Jin, H.Z.; Son, P.T.; Lee, J.H.; Hong, Y.S.; Lee, J.J. ent-Kaurane diterpenoids from croton tonkinensis inhibit LPS-induced NF-kappaB activation and NO production. J. Nat. Prod., 2003, 66, 1217-1220.
69. Sun, H.D.; Huang, S.X.; Han, Q.B. Diterpenoids from Isodon species and their biological activities. Nat. Prod. Rep., 2006, 23, 673-698.
70. Hwang, B.Y.; Lee, J.H.; Koo, T.H.; Kim, H.S.; Hong, Y.S.; Ro, J.S.; Lee, K.S.; Lee, J.J. Kaurane diterpenes from Isodon japonicus inhibit nitric oxide and prostaglandin E2 production and NF-kappaB activation in LPS-stimulated macrophage RAW264.7 cells. Planta Med., 2001, 67, 406-410.
71. Lee, J.W.; Lee, M.S.; Kim, T.H.; Lee, H.J.; Hong, S.S.; Noh, Y.H.; Hwang, B.Y.; Ro, J.S.; Hong, J.T. Inhibitory effect of inflexinol on nitric oxide generation and iNOS expression via inhibition of NF-kappaB activation. Mediators Inflamm., 2007, 93148.
72. Brinker, A.M.; Ma, J.; Lipsky, P.E.; Raskin, I. Medicinal chemistry and pharmacology of genus Tripterygium (Celastraceae). Phytochemistry, 2007, 68, 732-766.
73. Lin, N.; Sato, T.; Ito, A. Triptolide, a novel diterpenoid triepoxide from Tripterygium wilfordii Hook. f., suppresses the production and gene expression of pro-matrix metalloproteinases 1 and 3 and augments those of tissue inhibitors of metalloproteinases 1 and 2 in human synovial fibroblasts. Arthritis Rheum., 2001, 44, 2193-2200.
74. Liu, H.; Liu, Z.H.; Chen, Z.H.; Yang, J.W.; Li, L.S. Triptolide: a potent inhibitor of NF-kappa B in T-lymphocytes. Acta Pharmacol. Sin., 2000, 21, 782-786.
75. Jang, B.C.; Lim, K.J.; Choi, I.H.; Suh, M.H.; Park, J.G.; Mun, K.C.; Bae, J.H.; Shin, D.H.; Suh, S.I. Triptolide suppresses interleukin-1beta-induced human beta-defensin-2 mRNA expression through inhibition of transcriptional activation of NF-kappaB in A549 cells. Int. J. Mol. Med., 2007, 19, 757-763.
76. McCallum, C.; Kwon, S.; Leavitt, P.; Shen, D.M.; Liu, W.; Gurnett, A. Triptolide binds covalently to a 90 kDa nuclear protein. Role of epoxides in binding and activity. Immunobiology, 2007, 212, 549-556.
77. Corea, G.; Fattorusso, E.; Lanzotti, V.; Di Meglio, P.; Maffia, P.; Grassia, G.; Ialenti, A.; Ianaro, A. Discovery and biological evaluation of the novel naturally occurring diterpene pepluanone as anti-inflammatory agent. J. Med. Chem., 2005, 48, 7055-7062.
78. Nagle, D.G.; Zhou, Y.D.; Mora, F.D.; Mohammed, K.A.; Kim, Y.P. Mechanism targeted discovery of antitumor marine natural products. Curr. Med. Chem., 2004, 11, 1725-1756.
79. Newman, D.J.; Cragg, G.M. Marine natural products and related compounds in clinical and advanced preclinical trials. J. Nat. Prod., 2004, 67, 1216-1238.
80. Amigo, M.; Paya, M.; Braza-Boils, A.; De Rosa, S.; Terencio, M.C. Avarol inhibits TNF-alpha generation and NF-kappaB activation in human cells and in animal models. Life Sci., 2008, 82, 256-264.
81. Folmer, F.; Jaspars, M.; Dicato, M.; Diederich, M. Marine natural products as targeted modulators of the transcription factor NF-kappaB. Biochem. Pharmacol., 2008, 75, 603-617.
82. Lucas, R.; Casapullo, A.; Ciasullo, L.; Gomez-Paloma, L.; Paya, M. Cycloamphilectenes, a new type of potent marine diterpenes: inhibition of nitric oxide production in murine macrophages. Life Sci., 2003, 72, 2543-2552.
83. Gilmore, T.D.; Herscovitch, M. Inhibitors of NF-kappaB signaling: 785 and counting. Oncogene, 2006, 25, 6887-6899.