Flavocoxid, a dual inhibitor of cyclooxygenase and 5-lipoxygenase, blunts pro-inflammatory phenotype activation in endotoxin-stimulated macrophages

British Journal of Pharmacology

Volumn 157, Issue 8, 2009, Pages 1410-1418

  Altavilla, D ^a   Squadrito, F ^a   Bitto, A ^a   Polito, F ^a   Burnett, B P ^b   Di Stefano, V ^a   Minutoli, L ^a  

^a UNIVERSITY OF MESSINA   (Italy)

^b PRIMUS PHARMACEUTICALS INC   (United States)

Author keywords

5 LOX; COX; Dual inhibitor; Flavocoxid; Inflammation; INOS; Limbrel; Medical food; NF kB; TNF a

Indexed keywords

ARACHIDONATE 5 LIPOXYGENASE; CYCLOOXYGENASE 1; CYCLOOXYGENASE 2; FLAVOCOXID; I KAPPA B ALPHA; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INDUCIBLE NITRIC OXIDE SYNTHASE; LEUKOTRIENE B4; LIPOXYGENASE INHIBITOR; MALONALDEHYDE; MESSENGER RNA; NITRITE; PROSTAGLANDIN E2; PROSTAGLANDIN SYNTHASE INHIBITOR; SALMONELLA ENDOTOXIN; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANTIINFLAMMATORY ACTIVITY; ARTICLE; CELL VIABILITY; CONTROLLED STUDY; CYTOKINE PRODUCTION; CYTOPLASM; ENZYME ACTIVATION; ENZYME INHIBITION; GENE EXPRESSION; MACROPHAGE ACTIVATION; MALE; NONHUMAN; PERITONEUM MACROPHAGE; PHENOTYPE; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN EXPRESSION; RAT; SALMONELLA ENTERITIDIS;

ANIMALS; ARACHIDONATE 5-LIPOXYGENASE; CATECHIN; CELL SURVIVAL; CYCLOOXYGENASE 2; CYCLOOXYGENASE INHIBITORS; DINOPROSTONE; DRUG COMBINATIONS; ENZYME-LINKED IMMUNOSORBENT ASSAY; FLAVONOIDS; I-KAPPA B PROTEINS; LIPOPOLYSACCHARIDES; MACROPHAGES, PERITONEAL; MALE; NITRIC OXIDE SYNTHASE TYPE II; RATS; RATS, SPRAGUE-DAWLEY; TUMOR NECROSIS FACTOR-ALPHA;

EID: 67449098178     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/j.1476-5381.2009.00322.x     Document Type: Article

References (61)

1. Adams LS, Seeram NP, Hardy ML, Catherine Carpenter C, Heber D (2006). Analysis of the interactions of botanical extract combinations against the viability of prostate cancer cell lines. Evid Based Complement Alternat Med 3 (1): 117-124.
2. Aktan F (2004). iNOS-mediated nitric oxide production and its regulation. Life Sci 75: 639-653.
3. Bäck M (2008). Inflammatory signaling through leukotriene receptors in atherosclerosis. Curr Atheroscler Rep 10: 244-251.
4. Baldwin AS Jr (1996). The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol 14: 649-683.
5. Baldwin AS (2001). The transcription factor NF-kB and human disease. J Clin Invest 107: 3-6.
6. Bauer R (1999). Cyclooxygenase and 5-lipoxygenase as targets for medicinal plant research. In: Bohlin L, Bruhn JG (eds). Bioassay Methods in Natural Product Research and Drug Development. Kluwer Academic Publishers: Dortrecht/Boston, MA/London, pp. 128-132.
7. Botting RM (2006). Inhibitors of cyclooxygenases: mechanisms, selectivity and uses. J Physiol Pharmacol 57 (Suppl. 5): 113-124.
8. Brune K (2004). Safety of anti-inflammatory treatments-new ways of thinking. Rheumatology 43: 116-120.
9. Burdan F, Chałas A, Szumiło J (2006). Cyclooxygenase and pros-tanoids-biological implications. Postepy Hig Med Dosw 60: 129-141.
10. Burnett BP, Jia Q, Zhao Y, Levy RM (2007). A medicinal extract of Scutellaria baicalensis and Acacia catechu acts as a dual inhibitor of cyclooxygenase and 5-lipoxygenase to reduce inflammation. J Med Food 10: 442-451.
11. Celotti F, Durand T (2003). The metabolic effects of inhibitors of 5-lipoxygenase and of cyclooxygenase 1 and 2 are an advancement in the efficacy and safety of anti-inflammatory therapy. Prostaglan-dins Other Lipid Mediat 71: 147-162.
12. Celotti F, Laufer S (2001). Anti-inflammatory drugs: new multitarget compounds to face an old problem. The dual inhibition concept. Pharmacol Res 43: 429-436.
13. Chao JI, Su WC, Liu HF (2007). Baicalein induces cancer cell death and proliferation retardation by the inhibition of CDC2 kinase and survivin associated with opposite role of p38 mitogen-activated protein kinase and AKT. Mol Cancer Ther 6 (11): 3039-3048.
14. Chou TC, Chang LP, Li CY, Wong CS, Yang SP (2003). The antiinflam-matory and analgesic effects of baicalin in carrageenan evoked thermal hyperalgesia. Anesth Analg 97: 1724-1729.
15. Clària J, Romano M (2005). Pharmacological intervention of cyclooxygenase-2 and 5-lipoxygenase pathways. Impact on inflammation and cancer. Curr Pharm Des 11: 3431-3447.
16. Cunha FQ, Poole S, Lorenzetti BB, Ferreira SH (1992). The pivotal role of tumour necrosis factor alpha in the development of inflammatory hyperalgesia. Br J Pharmacol 107: 660-664.
17. De Clerq E (2005). Current lead natural products for the chemotherapy of human immunodeficiency virus (HIV) infection. Med Res Rev 20: 323-349.
18. Ford-Hutchinson AW, Bray MA, Doig MV, Shipley ME, Smith MJ (1980). Leukotriene B, a potent chemokinetic and aggregating substance released from polymorphonuclear leukocytes. Nature 286: 264-265.
19. Ge QF, Hu X, Ma ZQ, Liu JR, Zhang WP, Chen Z et al. (2007). Baicalin attenuates oxygen-glucose deprivation-induced injury via inhibiting NMDA receptor-mediated 5-lipoxygenase activation in rat cortical neurons. Pharmacol Res 55 (2): 148-157.
20. Hinz B, Brune K (2002). Cyclooxygenase-2-10 years later. J Pharmacol Exp Ther 300: 367-375.
21. Huang Y, Tsang SY, Tao X, Chen ZY (2005). Biological properties of baicalein in cardiovascular system. Curr Drug Targets Cardiovasc Hae-matol Disord 5: 177-184.
22. Hudson N, Balsitis M, Everitt S, Hawkey CJ (1993). Enhanced gastric mucosa LTB4 synthesis in patients taking non-steroidal anti-inflammatory drugs. Gut 34: 742-747.
23. Kandaswami C, Lee LT, Lee PP, Hwang JJ, Ke FC, Huang YT et al. (2005). The antitumor activities of flavonoids. In Vivo 19: 895-909.
24. Khanapure SP, Garvey DS, Janero DR, Letts LG (2007). Eicosanoids in inflammation: biosynthesis, pharmacology, and therapeutic frontiers. Curr Top Med Chem 7: 311-340.
25. Kopp EB, Ghosh S (1995). NF-kappa B and rel proteins in innate immunity. Adv Immunol 58: 1-27.
26. Krahauer T, Li BQ, Young HA (2001). The flavonoid baicalin inhibits superantigen-induced inflammatory cytokines and chemokines. FEBS Lett 500: 52-55.
27. Kuehl FA Jr, Egan RW (1980). Prostaglandins, arachidonic acid and inflammation. Science 210: 978-984.
28. Leone S, Ottani A, Bertolini A (2007). Dual acting anti-inflammatory drugs. Curr Top Med Chem 7: 265-275.
29. Levy R, Saikovsky R, Shmidt E, Khokhlov A (2007). Safety, efficacy and acceptability of flavocoxid (Limbrel™) compared with naproxen in subjects with osteoarthritis of the knee: a pilot study. Osteoarthritis Cartilage 15 (Suppl. B): B91. DOI: 10.1016/ S1063-4584(07)61370-61373 See also http://clinicaltrials.gov/ct/show/NCT00294125
30. Lin YL, Lin JK (1997). (-)-Epigallocatechin-3-gallate blocks the induction of nitric oxide synthase by down-regulating lipopolysaccharide-induced activity of transcription factor nuclear factor-kappaB. Mol Pharmacol. 52 (3): 465-472.
31. Liu LL, Gong LK, Wang H, Xiao Y, Wu XF, Zhang YH et al. (2008). Baicalin inhibits macrophage activation by lipopolysaccharide and protects mice from endotoxin shock. Biochem Pharmacol 75 (4): 914-922.
32. van Loon IM (1997). The golden root: clinical applications of Scutel-laria baicalensis GEORGI flavonoids as modulators of the inflammatory response. Altern Med Rev 2: 472-480.
33. Lotito SB, Fraga CG (2000). Catechins delay lipid oxidation and a-tocopherol and b-carotene depletion following ascorbate depletion in human plasma. Proc Soc Exp Biol Med 225: 32-38.
34. Lowenstein CJ, Alley EW, Raval P, Snowman AM, Snyder SH, Russell SW et al. (1993). Macrophage nitric oxide synthase gene: two upstream regions mediate induction by interferon gamma and lipopolysaccharide. Proc Natl Acad Sci USA 90: 9730-9734.
35. Maccarrone M, Taccone-Gallucci M, Meloni C, Cococcetta N, Di Vil-lahermosa SM, Casciani CU et al. (1999). Activation of 5-lipoxygenase and related cell membrane lipoperoxidation in hemodialysis patients. J Am Soc Nephrol 10 (9): 1991-1996. (Pubitemid 29402521)
36. Mao TK, van de Water J, Keen CL, Schmitz HH, Gershwin ME (2002). Modulation of TNF-a secretion in peripheral blood mononuclear cells by cocoa flavanols and procyanidins. Dev Immunol 9 (3): 135-141.
37. Mariotto S, Suzuki Y, Persichini T, Colasanti M, Suzuki H, Cantoni O (2007). Cross-talk between NO and arachidonic acid in inflammation. Curr Med Chem 14: 1940-1944.
38. Martel-Pelletier J, Lajeunesse D, Reboul P, Pelletier JP (2003). Therapeutic role of dual inhibitors of 5-LOX and COX, selective and non-selective non-steroidal anti-inflammatory drugs. Ann Rheum Dis 62: 501-509.
39. Maxis K, Delalandre A, Martel-Pelletier J, Pelletier JP, Duval N, Lajeu-nesse D (2006). The shunt from the cyclooxygenase to lipoxygenase pathway in human osteoarthriticsubchondral osteoblasts is linked with a variable expression of the 5-lipoxygenase-activating protein. Arthritis Res Ther 8: R181.
40. Mehrabian M, Allayee H, Wong J, Shi W, Wang XP, Shaposhnik Z et al. (2002). Identification of 5-lipoxygenase as a major gene contributing to atherosclerosis susceptibility in mice. Circ Res 91: 120-126.
41. Mittal A, Pate MS, Wylie RC, Tollefsbol TO, Katiyar SK (2004). EGCG down-regulates telomerase in human breast carcinoma MCF-7 cells, leading to suppression of cell viability and induction of apoptosis. Int J Oncol 24 (3): 703-710.
42. Mosmann T (1983). Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65: 55-63.
43. Muthoh M, Takahashi M, Fukuda K, Komatsu H, Enya T, Matsushima-Hibiya Y et al. (2000). Suppression by flavonoids of cyclooxygenase-2 promoter-dependent transcriptional activity in colon cancer cells: structure-activity relationship. Jpn J Cancer Res 91 (7): 686-691. (Pubitemid 30612352)
44. Nam NH (2006). Naturally occurring NF-kB inhibitors. Mini Rev Med Chem 6: 945-951.
45. Niederberger E, Tegeder I, Vetter G, Schmidtko A, Schmidt H, Euchen-hofer C et al. (2001). Celecoxib loses its anti-inflammatory efficacy at high doses through activation of NF-kappaB. FASEB J 15: 1622-1624.
46. Pahl HL (1999). Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene 18: 6853-6866.
47. Pantano C, Reynaert NL, van der Vliet A, Janssen-Heininger YM (2006). Redox-sensitive kinases of the nuclear factor-kappaB signaling pathway. Antioxid Redox Signal 8: 1791-1806.
48. Perazella MA, Eras J (2000). Are selective COX-2 inhibitors nephro-toxic? Am J Kidney Dis 35: 937-940.
49. Peters-Golden M (2008). Expanding roles for leukotrienes in airway inflammation. Curr Allergy Asthma Rep 8: 367-373.
50. Rodrigo R, Bosco C (2006). Oxidative stress and protective effects of polyphenols: comparative studies in human and rodent kidney. A review. Comp Biochem Physiol C Toxicol Pharmacol 142: 317-327.
51. Sanghi S, MacLaughlin EJ, Jewell CW, Chaffer S, Naus PJ, Watson LE et al. (2006). Cyclooxygenase-2 inhibitors: a painful lesson. Cardio-vasc Hematol Disord Drug Targets 6 (2): 85-100.
52. Shelly MM, Hawkey CJ (2003). Cox-Lox inhibition: current evidence for an emerging new therapy. Int J Clin Pract 57: 301-304.
53. Shieh DE, Liu LT, Lin CC (2000). Antioxidant and free radical scavenging effects of baicalein, baicalin and wogonin. Anticancer Res 20: 281-286.
54. Tegeder I, Niederberger E, Vetter G, Brautigam L, Geisslinger G (2001). Effects of selective COX-1 and-2 inhibition on formalin-evoked nociceptive behaviour and prostaglandin E(2) release in the spinal cord. J Neurochem 79: 777-786.
55. Ueda S, Nakamura H, Masutani H, Sasada T, Takabayashi A, Yamaoka Y et al. (2002). Baicalin induces apoptosis via mitochondrial pathway as prooxidant. Mol Immunol 38 (10): 781-791.
56. Wagner H (1993). Leading structures of plant origin for drug development. J Ethnopharmacol 38: 105-112.
57. Wang GF, Wu ZF, Wan L, Wang QT, Chen FM (2006). Influence of baicalin on the expression of receptor activator of nuclear factor-kB ligand in cultured human periodontal ligament cells. Pharmacology 77: 71-77.
58. Wu WB, Chiang HS, Fang JY, Chen SK, Chieh-Chen Huang CC, Hung CF (2006). (+)-Catechin prevents ultraviolet B-induced human kera-tinocyte death via inhibition of JNK phosphorylation. Life Sci 79 (8): 801-807.
59. Xie Q, Nathan C (1994). The high-output nitric oxide pathway: role and regulation. J Leukoc Biol 56: 576-582. (Pubitemid 24348815)
60. Yokomizo T, Izumi T, Chang K, Takuwa Y, Shimizu T (1997). A G-protein-coupled receptor for leukotriene B4 that mediates chemotaxis. Nature 387: 620-624.
61. Zamora R, Vodovotz Y, Billiar TR (2000). Inducible nitric oxide syn-thase and inflammatory diseases. Mol Med 6: 347-373.