Natural Inhibitors of Tumour Necrosis Factor-α Production, Secretion and Function

Abstract

Tumour necrosis factor-α (TNF), originally discovered by its antitumor activity, is one of the most pleotropic cytokines acting as a host defence factor in immunologic and inflammatory responses. Although the antitumour activity and mediation of inflammation by TNF could be beneficial to the host, unregulated TNF is now known to be the basis for development of various diseases including septic shock, the wasting disease, cachexia, and various inflammatory and/or autoimmune diseases. With an attempt to find potential therapeutic agents for TNF-mediated diseases, research during the last decade has led in the identification of well over one hundred natural inhibitors of either TNF production/secretion or function. This review summarises the structures, mechanism of action and therapeutic potential of these natural products.

TNF - natural inhibitors - adhesion molecules - NF-κB - cAMP - inflammation - cytotoxicity

References

• 1 Vassalli  P.. The pathology of tumor necrosis factors.  Annu. Rev. Immunol.. 1992;;  10 411-52
• 2 Tracy  K J,, Cerami  A.. Tumor necrosis factor - a pliotropic cytokine and therapeutic agent.  Annu. Rev. Med.. 1994;;  45 491-3
• 3 Bevilacqua  M P,, Nelson  R M,, Mannori  G M,, Cecconi  O.. Endothelial-leukocyte adhesion molecules in human disease.  Annu. Rev. Med.. 1994;;  45 361-78
• 4 Argiles  J M,, Lopez-Soriano  J,, Busquets  S,, Lopez-Soriano  F J.. Journey from cachexia to obesity by TNF.  FASEB J.. 1997;;  11 743-51
• 5 Garcia-Martinez  C,, Costelli  P,, Lopez-Soriano  F J,, Argiles  J M.. Is TNF really involved in cachexia?.  Cancer Invest.. 1997;;  15 47-54
• 6 Murphy  K,, Haudek  S B,, Thompson  M,, Giroir  B P.. Molecular biology of septic shock. New horizons.  Sci. Practice Acute Med.. 1998;;  6 181-93
• 7 Medana  I M,, Hunt  N H,, Chaudhri  G.. TNF expression in the brain during fatal murine cerebral malaria - Evidence for production by microglia and astrocytes.  Am. J. Pathol.. 1997;;  150 1473-86
• 8 Bjornsdottir  U S,, Cypcar  D M.. Asthma: an inflammatory mediator soup.  Allergy. 1999;;  54 55-61
• 9 Sekut  L,, Connolly  K M.. Pathophysiology and regulation of TNF in inflammation.  Drug News Perspectives. 1996;;  9 261-9
• 10 Young  P R.. Pharmacological modulation of cytokine action and production through signaling pathways.  Cytokine & Growth Factor Rev.. 1999;;  9 239-57
• 11 Eugui  E M,, Delustro  B,, Rouhafza  S,, Ilnicka  M,, Lee  S W,, Wilhelm  R,, Allison  A A.. Some antioxidants inhibit, in a coordinate fashion, the production of TNF, IL-1β, and IL-6 by human peripheral-blood mononuclear cells.  International Immunol.. 1994;;  6 409-22
• 12 Abe  Y,, Hashimoto  S,, Horie  T.. Curcumin inhibition of inflammatory cytokine production by human peripheral blood monocytes and alveolar macrophages.  Pharmacol. Res.. 1999;;  39 41-7
• 13 Mrowietz  U,, Jessat  H,, Schwarz  A,, Schwarz  T.. Anthralin (Dithranol) in vitro inhibits human monocytes to secrete IL-6, IL-8 and TNF-α, but not IL-1.  Br. J. Dermatol.. 1997;;  136 542-7
• 14 Li  Z Y,, Davis  G S,, Mohr  C,, Nain  M,, Gemsa  D.. Inhibition of LPS-induced TNF by colchicine and other microtubule disrupting drugs.  Immunobiology. 1996;;  195 624-39
• 15 Ju  D W,, Jheng  Q Y,, Cao  X T,, Fang  J,, Wang  H B.. Esculentoside A inhibits TNF, IL-1 and IL-6 production induced by LPS in mice.  Pharmacology. 1998;;  56 187-95
• 16 Shinji  H,, Akagawa  K S,, Yoshida  T.. Cytochalasin-D inhibits LPS-induced TNF production in macrophages.  J. Leukocyte Biol.. 1993;;  54 336-42
• 17 Moon  E Y,, Rhee  D K,, Pyo  S.. In vitro suppressive effect of aflatoxin B-1 on murine peritoneal macrophage functions.  Toxicology. 1999;;  133 171-9
• 18 Habtemariam  S.. Extract of corn silk (stigma of Zea mays) inhibits the TNF and bacterial lipopolysaccharide-induced cell adhesion and ICAM-1 expression.  Planta Med.. 1998;;  64 314-8
• 19 Wadsworth  T L,, Koop  D R.. Effects of the wine polyphenolics quercetin and resveratrol on pro-inflammatory cytokine expression in RAW 264.7 macrophages.  Biochem. Pharmacol.. 1999;;  57 941-9
• 20 Lee  H J,, Kim  N Y,, Jang  M K,, Son  H J,, Kim  K M,, Sohn  D H, et al.. A sesquiterpene, dehydrocostus lactone, inhibits the expression of inducible nitric oxide synthase and TNF in LPS-activated macrophages.  Planta Med.. 1999;;  65 104-8
• 21 Kawada  N,, Seki  S,, Inoue  M,, Kuroki  T.. Effect of antioxidants, resveratrol, quercetin, and N-acetylcysteine, on the functions of cultured rat hepatic stellate cells and Kupffer cells.  Hepatology. 1998;;  27 1265-74
• 22 Shames  B D,, Selzman  C H,, Pulido  E J,, Meng  X Z,, Meldrum  D R,, McIntyre  R C,, Harken  A H,, Banerjee  A.. LPS-induced NF-κB activation and TNF release in human monocytes are protein tyrosine kinase dependent and protein kinase C independent.  J. Surg. Res.. 1999;;  83 69-74
• 23 Schreiber  S.. Activation of NF-κB as a target for anti-inflammatory therapy.  Gut. 1999;;  44 309-10
• 24 Siebenlist  U,, Franzo  G,, Brown  K.. Structure, regulation and function of NF-κB.  Annu. Rev. Cell Biol.. 1994;;  10 405-55
• 25 Vittimberga  F J,, McDade  T P,, Perugini  R A,, Callery  M P.. Sodium salicylate inhibits macrophage TNF production and alters MAPK activation.  J. Surg. Res.. 1999;;  84 143-9
• 26 Shackelford  R E,, Alford  P B,, Xue  Y,, Thai  S F,, Adams  D O,, Pizzo  S.. Aspirin inhibits TNF gene expression in murine tissue macrophages.  Mol. Pharmacol.. 1997;;  52 421-9
• 27 Tsai  S H,, Liang  Y C,, LinShiau  S Y,, Lin  J K.. Suppression of TNF-mediated NF-κB activity by myricetin and other flavonoids through downregulation the activity of IKK in ECV304 cells.  J. Cellular Biochem.. 1999;;  74 606-15
• 28 Xu  Y X,, Pindolia  K R,, Janakiraman  N,, Chapman  R A,, Gautam  S C.. Curcumin inhibits Il1-α and TNF induction of AP-1 and NF-κB DNA-binding activity in bone marrow stromal cells.  Hematology Mol. Hematology. 1998;;  11 49-62
• 29 Yang  F G,, DeViller  W JS,, McClain  C J,, Varilek  G W.. The green tea polyphenol, EGCG inhibits LPS-mediated NF-κB activation and TNF-α production in the macrophage cell line, RAW264.7.  FASEB J.. 1998;;  12 S258
• 30 Page  S,, Fisher  C,, Baumgartner  B,, Haas  M,, Kreusel  U,, Loidl  G,, Hayan  M,, Zieglerheitbrock  H WL.. 4-Hydroxynonenal prevents NF-κB activation and TNF expression by inhibiting IκB phosphorylation and subsequent proteolysis.  J. Biol. Chem.. 1999;;  274 11611-8
• 31 Singh  S,, Natarajan  K,, Aggarwal  B B.. Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is a potent inhibitor of nuclear transcription factor-κB activation by diverse agents.  J. Immunol.. 1996;;  157 4412-20
• 32 Yu  R,, Park  J W,, Kurata  T,, Erickson  K L.. Modulation of select immune responses by dietary capsaicin.  Int. J. Vitam. Nutr. Res.. 1998;;  68 114-9
• 33 Roy  S,, Cain  K J,, Chapin  R B,, Charboneau  R G,, Barke  R A.. Morphine modulates NF-κB activation in macrophages.  Biochem. Biophys. Res. Commun.. 1998;;  245 392-6
• 34 Bencsics  A,, Elenkov  I J,, Vizi  E S.. J. Effect of morphine on lipopolysaccharide-induced TNF-α production in vitro: Involvement of the sympathetic nervous system.  Neuroimmunology. 1997;;  73 1-6
• 35 Vayssier  M,, Favatier  F,, Pinot  F,, Bachelet  N,, Polla  B S.. Tobacco smoke induced coordinate activation of HSF and inhibition of NF κB in human monocytes: Effects of TNFα release.  Biochem. Biophys. Res. Commun.. 1999;;  252 249-56
• 36 Madretsma  G S,, Donze  G J,, VanDijk  A PM,, Tak  C JAM,, Wilson  J HP,, Zijlstra  F J.. Nicotine inhibits the in vitro production of IL-2 and TNF-α by human mononuclear cells.  Immunopharmacology. 1996;;  35 47-51
• 37 Pyatt  D W,, Stillman  W S,, Irons  R D.. Hydroquinone, a reactive metabolite of benzene, inhibits NF-κB in primary human CD4⁺ T lymphocytes.  Toxicol. Appl. Pharmacol.. 1998;;  149 178-84
• 38 Siegmund  B,, Eigler  A,, Moeller  J,, Greten  T F,, Hartmann  G,, Endres  S.. Suppression of TNF-α production by interleukin-10 is enhanced by cAMP-elevating agents.  Eur. J. Pharmacol.. 1997;;  321 231-9
• 39 Wang  L Z,, Liu  Y Q,, Cui  Y H,, Zhu  F H,, Wang  B S,, Lun  N.. Effects of dexamethasone, cyprohepatidine, anisodamine, and dinoprostone on TNF production in endotoxic shock.  Acta Pharmacol. Sin.. 1999;;  20 171-4
• 40 Zhang  L M,, Castresana  M R,, Shaker  I J,, Dalton  M L,, Leeper-Woodford  S K,, Newman  W H.. Increased intracellular cyclic adenosine 3′,5′-monophosphate inhibits release of TNF-α from human vascular tissue and cultured smooth muscle cells.  Critical Care Med.. 1997;;  25 1855-61
• 41 Schudt  C,, Tenor  H,, Hatzelmann  A.. PDE isoenzymes as targets for antiasthma drugs.  Eur. Resp. J.. 1995;;  8 1179-83
• 42 Entzian  P,, Bitter-Suermann  S,, Burdon  D,, Ernst  M,, Schlaak  M,, Zabel  P.. Differences in the anti-inflammatory effects of theophylline and pentoxifylline: important for the development of asthma therapy?.  Allergy. 1998;;  53 749-54
• 43 Manthey  J A,, Grhmann  K,, Montanari  A,, Ash  K,, Manthey  C L.. Polymethoxylated flavones derived from citrus suppress TNF-α expression by human monocytes.  J. Nat. Prod.. 1999;;  62 441-4
• 44 Cho  J Y,, Park  J,, Yoo  E S,, Yoshikawa  K,, Baik  K U,, Lee  J,, Park  M H.. Inhibitory effect of lignans from the rhizomes of Coptis japonica var. dissecta on TNF production in lipopolysaccharide-stimulated RAW264.7 cells.  Arch. Pharmacal Res.. 1998;;  21 12-6
• 45 Chae  S H,, Kim  P S,, Cho  J Y,, Park  J S,, Lee  J H,, Yoo  E S et al.. Isolation of inhibitory compounds on TNF production from Magnolia fargeslii. .  Arch. Pharmacal Res.. 1998;;  21 67-9
• 46 Kawaguchi  K,, Kikuchi  S,, Hasegawa  H,, Maruyama  H,, Morita  H,, Kumazawa  Y.. Suppression of lipopolysaccharide-induced TNF release and liver injury in mice by naringin.  Eur. J. Pharmacol.. 1999;;  368 245-50
• 47 Fujiki  H,, Suganuma  M,, Okabe  S,, Sueoka  N,, Komori  A,, Sueoka  E, et al.. Cancer inhibition by green tea.  Mutat. Res. Fund. Mol. Mech. Mutagenesis. 1998;;  402 307-10
• 48 Nomura  T,, Hano  Y,, Aida  M.. Isoprenoid-substituted flavonoids from Artocarpus plants (Moraceae).  Heterocycles. 1998;;  47 1179-205
• 49 Zi  X L,, Mukhater  H,, Agarwal  R.. Novel cancer chemopreventive effects of a flavonoid antioxidant silymarin: Inhibition of mRNA expression of an endogenous tumor promoter TNF-α.  Biochem. Biophys. Res. Commun.. 1997;;  239 334-9
• 50 Sheng  C Y,, Gao  W Y,, Guo  Z R,, He  L X.. Anisodamine restores bowel circulation in burn shock.  Burns. 1997;;  23 142-6
• 51 Maruyama  N,, Kakuta  Y,, Yamauchi  K,, Ohkawara  Y,, Aizawa  T,, Nara  M, et al.. Quinine inhibits production of tumour necrosis factor-α from human alveolar macrophages.  Am. J. Resp. Cell Mol. Biol.. 1994;;  10 514-20
• 52 Onai  N,, Tsunokawa  Y,, Suda  M,, Watanabe  N,, Nakamura  K,, Sugimoto  Y,, Kobayashi  Y.. Inhibitory effects of bisbenzylisoquinoline alkaloids on induction of proinflammatory cytokines, interleukin-10 and TNF.  Plnata Med.. 1995;;  61 497-501
• 53 Rao  P,, Falk  L A,, Dougherty  S F,, Sawada  T,, Pluznik  D H.. Colchicine down-regulates lipopolysaccharide-induced granulocyte-macrophage colony-stimulating factor production in murine macrophages.  J. Immunol.. 1997;;  159 3531-9
• 54 Cho  J Y,, Park  J S,, Yoo  E S,, Baik  K U,, Jung  J H,, Lee  J S,, Park  M H.. Inhibitory effect of sesquiterpene lactones from Saussurea lappa on TNF production in murine macrophage-like cells.  Planta Med.. 1998;;  64 594-7
• 55 Endres  S,, Ghorbani  R,, Kelley  V E,, Georgilis  K,, Lonnemann  G,, VanDer-Meer  J WM, et al.. The effect of dietary supplementation with N-3 poly-unsaturated fatty acid on the synthesis of IL-1 and TNF by mononuclear cells.  New. Eng. J. Med.. 1989;;  320 265-70
• 56 Cabral  G A,, Toney  D M,, Fischerstenger  K,, Harrison  M P,, Marcianocabral  F.. Anandamide inhibits macrophage-mediated killing of TNF-sensitive cells.  Life Sci.. 1995;;  56 2065-72
• 57 Hase  K,, Xiong  Q B,, Basnet  P,, Namura  T,, Kadota  S.. Inhibitory effect of tetrahydrowertianolin on TNF-dependent hepatic apoptosis in mice.  Biochem. Pharmacol.. 1999;;  57 1431-7
• 58 Garcia  J EL,, Rodrriguez  F M,, Lopez  A J,, Salgado  M JG., De-Cabo  M RM,, Losada  J P, et al.. Effect of cyclosporin A on inflammatory cytokine production by human alveolar macrophages.  Resp. Med.. 1998;;  92 722-8
• 59 Mazzucco  C E,, Warr  G.. Trichodimerol (EMS-182123) inhibits lipopolysaccharide-induced eicosanoid secretion in THP-1 human monocytic cells.  J. Leukocyte Biol.. 1996;;  60 271-7
• 60 Shapira  L,, Soskoline  W A,, Houri  Y,, Barak  V,, Halabi  A,, Stabholz  A.. Protection against endotoxic shock and lipopolysaccharide-induced local inflammation by tetracycline: Correlation with inhibition of cytokine secretion.  Infect. Immun.. 1996;;  64 825-8
• 61 Shapira  L,, Houri  Y,, Barak  V,, Soskoline  W A,, Halabi  A,, Stabholz  A.. Tetracycline inhibits porphyromonas gingivalis lipopolysaccharide-induced lesions in vivo and TNF processing in vitro.  J. Periodental Res.. 1997;;  32 183-8
• 62 Zheng  Z M,, Specter  S C.. δ ⁹-Tetrahydrocannabinol suppresses TNF maturation and secretion but not its transcription in mouse macrophages.  Int. J. Immunopharmacol.. 1996;;  18 53-68
• 63 Schultz  M J,, Speelman  P,, Zaat  S,, VanDeventer  S JH,, Vander-Pool  T.. Erythromycin inhibits TNF and interleukin-6 production induced by heat-killed Streptococcus pneumoniae in whole blood.  Antimicrob. Agents Chemother.. 1998;;  42 1605-9
• 64 Natarajan  K,, Natarjan  K,, Manna  S K,, Chaturvedi  M M,, Aggarwal  B B.. Protein tyrosine kinase inhibitors block TNF-induced activation of NF-κB, degradation of IκBα, nuclear translocation of p65, and subsequent gene expression.  Arch. Biochem. Biophys.. 1998;;  352 59-70
• 65 Morris  P E,, Olmstead  L E,, Howardcarroll  A E,, Dickens  G R,, Goltz  M L,, Countneyshapiro  C, et al.. In vitro and in vivo effects of genistein on murine alveolar macrophage TNF-α production.  Inflammation. 1999;;  23 231-9
• 66 Ruetten  H,, Thiemermann  C.. Effects of tyrophostins and genistein on the circulatory failure and organ dysfunction caused by endotoxin in the rat: a possible role for protein tyrosine kinase.  Br. J. Pharmacol.. 1997;;  122 59-70
• 67 Van Ostade  X.. Protein engineering of TNF and lyphotoxin.  Drug News Perspectives. 1995;;  8 69-79
• 68 Habtemariam  S.. Modulation of TNF-induced cytotoxicity by polyphenols.  Phytotherapy Res.. 1997;;  11 227-30
• 69 Oddonnell  V B,, Spycher  S,, Azzi  A.. Involvement of oxidants and oxidant-generating enzyme(s) in TNF-mediated apoptosis - Role for lipoxygenase pathway but not mitochondrial respiratory-chain.  Biochem. J.. 1995;;  310 133-41
• 70 Habtemariam  S.. Flavonoids as inhibitors or enhancers of the cytotoxicity of TNF in L-929 tumor cells.  J. Nat. Prod.. 1997;;  60 775-8
• 71 Sumitomo  M,, Tachilbabna  M,, Nakashima  J,, Murai  M,, Miyajima  A,, Kimura  F, et al.. An essential role for nuclear factor κB in preventing TNF-induced cell death in prostate cancer cells.  J. Urol.. 1999;;  161 674-9
• 72 Xu  Y,, Bialik  S,, Jones  B E,, Iimuro  Y,, Kitsis  R N,, Srinivasan  A, et al.. NF-κB inactivation converts a hepatocyte cell line TNF response from proliferation to apoptosis.  Am. J. Physiol.-Cell Physiol.. 1998;;  44 C1058-66
• 73 Mcdade  T P,, Perugini  R A,, Vittimberga  F J,, Carrigan  R C,, Callery  M P.. Salicylates inhibit NF-κB activation and enhance TNF-induced apoptosis in human pancreatic cancer cells.  J. Sug. Res.. 1999;;  83 56-61
• 74 Ward  C,, Chilvers  E R,, Lawson  M F,, Pryde  J G,, Fujihara  S,, Farrow  S N, et al.. NF-κB activation is a critical regulator of human granulocyte apoptosis in vitro. .  J. Biol. Chem.. 1999;;  274 4309-18
• 75 Hehner  S P,, Heinrich  M,, Bork  P M,, Vogt  M,, Ratter  F,, Lehmann  V, et al.. Sesquiterpene lactones specifically inhibit activation of NF-κB by preventing the degradation of IκBα and IκBβ.  J. Biol. Chem.. 1998;;  273 1288-97
• 76 Sueoka  E,, Sueoka  N,, Kai  Y,, Okabe  S,, Suganum  M,, Kanematsu  K, et al.. Anticancer activity of morphine and its synthetic derivative, KT-90, mediated through apoptosis and inhibition of NF-κB activation.  Biochem. Biophys. Res. Commun.. 1998;;  252 566-70
• 77 Sasaki  C Y,, Patek  P Q.. The involvement of protein-tyrosine kinase-activity in TNF resistance mechanism.  Proc. Soc. Exp. Biol. Med.. 1995;;  210 25-32
• 78 Niwa  M,, Hara  A,, Kanamori  Y,, Matsuno  H,, Kozawa  O,, Yoshimi  N, et al.. Inhibition of TNF-induced neutrophil apoptosis by cyclic AMP: involvement of caspase cascade.  Eur. J. Pharmacol.. 1999;;  371 59-67
• 79 Brekke  O L,, Espevic  T,, Bjerve  K S.. Butylated hydroxyanisole inhibits tumour necrosis factor-induced cytotoxicity and arachidonic acid release.  Lipids. 1994;;  29 91-102
• 80 Hofsli  E,, Waage  A.. Effect of pyridoxine on TNF activities in vitro.  Biotherapy. 1992;;  5 285-90
• 81 Hughes  T K,, Fulep  E.. Effects of retinoic acid (vitamin A) on TNF cytolytic action.  Biochem. Biophys. Res. Commun.. 1995;;  206 223-9
• 82 Li  J X,, Shi  Q,, Xiong  Q B,, Prasain  J K,, Tezuka  Y,, Hareyama  T, et al.. Tribulusamide A and B, new hepatoprotective lignanamides from the fruits of Tribulus terrestris: Indications of cytoprotective activity in murine hepatocyte culture.  Planta Med.. 1998;;  64 628-31
• 83 Matsuda  H,, Ninomiya  K,, Morikawa  T,, Yoshikawa  M.. Inhibitory effect and action mechanism of sesquiterpenes from Zedoariae rhizoma on D-galactosamine/lipopolysaccharide-induced liver injury.  Bioorg. Med. Chem. Lett.. 1998;;  8 339-44
• 84 Hase  K,, Li  J X,, Basnet  P,, Xiong  Q B,, Takamura  S,, Namba  T, et al.. Hepatoprotective principles of Swertia japonica on D-galactosamine/lipopolysaccharide-induced liver injury in mice.  Chem. Pharm. Bull.. 1997;;  45 1823-7
• 85 Leist  M,, Ganter  F,, Jilg  S,, Wendel  A.. Activation of the 55-kda receptor is necessary and sufficient for TNF-induced liver-failure, hepatocyte apoptosis, and nitrate release.  J. Immunol.. 1995;;  154 1307-16
• 86 Schleimer  R P,, Rutledge  B K.. Cultured human vascular endothelial cells acquire adhesiveness for neutrophils after stimulation with interleukin-1, endotoxin and tumour promoting phorbol diesters.  J. Immunol.. 1986;;  136 649-54
• 87 Murase  T,, Kume  N,, Hase  T,, Shibuya  Y,, Tokimitsu  I,, Kita  T.. Gallates inhibit cytokine-induced nuclear translocation of NF-κB and expression of leukocyte adhesion molecules in vascular endothelial cells.  Atherosclerosis Thrombosis Vascular Biol.. 1999;;  19 1412-20
• 88 Kumar  A,, Dhawan  S,, Agganwal  B B.. Emodin (3-methyl-1,6,8-trihydroxyanthraquinone) inhibits TNF-induced NF-κB activation, IκB degradation, and expression of cell surface adhesion proteins in human vascular endothelial cells.  Oncogene. 1988;;  17 913-8
• 89 Weber  C,, Erl  W,, Pietsch  A,, Weber  P C.. Aspirin inhibits NF-κB mobilisation and monocyte adhesion in stimulated human endothelial cells.  Circulation. 1995;;  91 1914-7
• 90 Kimura  Y,, Matsushita  N,, Okuda  H.. Effects of baicalein isolated from Scutellaria baicalensis on interleukin-1β and TNF-induced adhesion molecule expression in cultured human umbilical vein endothelial cells.  J. Ethnopharmacol.. 1997;;  57 63-7
• 91 Burke-Gaffney  A,, Hellwell  P G.. TNF-induced ICAM-1 expression in human vascular endothelial and lung epithelial cells: Modulation by tyrosine kinase inhibitors.  Br. J. Pharmacol.. 1996;;  119 1149-58
• 92 Chen  C C,, Rosenbloom  C L,, Anderson  D C,, Manning  A M.. Selective inhibition of E-selectin, VCAM-1, and ICAM-1 expression by inhibition of IκBα phosphorylation.  J. Immunol.. 1995;;  155 3538-45
• 93 Pierce  J W,, Road  M A,, Ding  H,, Luscinskas  F W,, Collins  T.. Salicylates inhibit IκBβ phosphorylation, ELAM expression, and neutrophil transmigration.  J. Immunol.. 1996;;  156 3961-9
• 94 Kumar  A,, Dhawan  S,, Hardegen  N J,, Aggarwal  B B.. Curcumin (diferuloylmethane) inhibition of TNF-mediated adhesion of monocytes to endothelial cells by suppression of cell surface expression of adhesion molecules and of nuclear factor-κB activation.  Biochem. Pharmacol.. 1998;;  55 775-83
• 95 Gerritsen  M E,, Carley  W W,, Ranges  G E,, Shen  C P,, Phan  S A,, Ligon  G F, et al.. Flavonoids inhibit cytokine-induced endothelial-cell adhesion protein gene-expression.  Am. J. Pathol.. 1995;;  147 278-92
• 96 Xu  Y X,, Pindolia  K R,, Janakiraman  N,, Noth  C J,, Chapman  R A,, Gautam  S C, et al.. Curcumin, a compound with anti-inflammatory and anti-oxidant properties, down-regulates chemokine expression in bone marrow stromal cells.  Exp. Heamatol.. 1997;;  25 413-22
• 97 Bork  P M,, Bacher  S,, Schmitz  M L,, Kaspers  U,, Heinrich  M.. Hypericin as a non-antioxidant inhibitor of NF-κB.  Planta Med.. 1999;;  65 297-300
• 98 Breton  J J,, Chabot-Fletcher  M C.. The natural product hymenialdisine inhibits interleukin-8 production in U937 cells by inhibition of NF-κB.  J. Pharmacol. Exp. Ther.. 1997;;  282 459-66
• 99 Qiu  D M,, Zhao  G H,, Aoki  Y,, Shi  L F,, Uyei  A,, Nazarian  S.. Immunosuppressant PG490 (triptolide) inhibits T-cell interleukin-2 expression at the level of purine-box/nuclear factor of activated T-cells and NF-κB transcriptional activation.  J. Biol. Chem.. 1999;;  274 13443-50
• 100 Sato  M,, Miyazaki  T,, Kambe  F,, Maeda  K,, Seo  H.. Quercetin, a bioflavonoid, inhibits the induction of interleukin-8 and monocyte chemoattractant protein-1 expression by TNF in cultured human synovial cells.  J. Rheumatol.. 1997;;  24 1680-4
• 101 Bierhaus  A,, Zhang  Y M,, Quehenberger  P,, Luther  T,, Haase  M,, Muller  M,, Mackman  N,, Ziegler  R,, Narworth  P P.. The dietary pigment curcumin reduces endothelial tissue factor gene expression by inhibiting binding of AP-1 to the DNA and activation of NF-κB.  Thromb. Haemostasis. 1997;;  77 772-82
• 102 Khalfoun  B,, Thibault  G,, Lebranchu  Y.. Docosahexaenoic acid and eicosahexaenoic acids inhibit in vitro human lymphocyte-endothelial cell adhesion.  Transplantation. 1996;;  62 1649-57
• 103 Carluccio  M A,, Massaro  M,, Bonfrate  C,, Siculella  L,, Maffia  M,, Nicolardi  G.. Oleic acid inhibits endothelial activation - A direct vascular antiatherogenic mechanism of a nutritional component in the mediterranean diet.  Arteriosclerosis thrombosis vascular biol.. 1999;;  19 220-8
• 104 Decateriona  R,, Cybulsky  M I,, Clinton  S K,, Gimbrone  M A,, Libby  P.. The ω-3 fatty acid docosahexaenoate reduces cytokine-induced expression of proatherogenic and proinflammatory proteins in human endothelial cells.  Arteriosclerosis Thrombosis. 1994;;  14 1829-36
• 105 Chaturvedi  M M,, Kumar  A,, Darney  B G,, Chainy  G BN,, Agarwal  S,, Aggarwal  B B.. Sanguinarine (pseudochelerythrine) is a potent inhibitor of NF-κB activation, iκBα phosphorylation, and degradation.  J. Biol. Chem.. 1997;;  272 30129-34
• 106 Lyss  G,, Knorre  A,, Schmidt  T J,, Pahl  H L,, Merfort  I.. The anti-inflammatory sesquiterpene lactone helenalin inhibits the transcription factor NF-κB by directly targeting p65.  J. Biol. Chem.. 1998;;  273 33508-16
• 107 May  M J,, Wheeler-Jones  P CD,, Pearson  J D.. Effects of protein tyrosine kinase inhibitors on cytokine-induced adhesion molecule expression by human umbilical vein endothelial cells.  Br. J. Pharmacol.. 1996;;  118 1761-71
• 108 Weber  C,, Negrescu  E,, Pietsch  A,, Frankenberger  M,, Zieglerheitbrock  H WL,, Sies  W, et al.. Inhibitors of protein-tyrosine kinase suppress TNF-stimulated induction of endotrhelial cell adhesion molecules.  J. Immunol.. 1995;;  155 445-51
• 109 Vanhinsbergh  V WM,, Vermeer  M,, Koolwijk  P,, Grimbergen  J,, Kooistra  T.. Genistein reduces TNF induced plasminogen activator inhibitor-1 transcription but not urokinase expression in human endothelial cells.  Blood. 1994;;  84 2984-91
• 110 Ferrero  M E,, Bertelli  A AE,, Fulgenzi  A,, Pellegatta  F,, Corsi  M,, Bonfrate  M, et al.. Activity in vitro of resveratrol on granulocyte and monocyte adhesion to endotheliam.  Am. J. Clin. Nutr.. 1998;;  68 1208-14
• 111 Oliver  V,, Parry  G CN,, Cobb  R R,, DeProst  D,, Mackman  N.. Elevated cAMP inhibits NF κB-mediated transcription in human monocyte cells and endothelial cells.  J. Biol. Chem.. 1996;;  271 20828-35
• 112 Panettieri  R A,, Lazaar  A L,, Albelda  S M.. Activation of cAMP-dependent pathways in human airway smooth-muscle cells inhibits the TNF-induced ICAM-1 and VCAM-1 expression and lymphocyte adhesion.  J. Immunol.. 1995;;  154 2358-65
• 113 Kitahara  M,, Mori  T.. Prostacyclin and prostaglandin E2 inhibit proinflammatory cytokine-induced MCSF production in cultured human glomerular mesangial cells.  Nephrology. 1997;;  3 541-7
• 114 Habtemariam  S.. Andrographolide inhibits the TNFI-induced upregulation of ICAM-1 expression and endothelial-monocyte adhesion.  Phytotherapy Res.. 1998;;  12 37-40
• 115 Kimura  Y,, Okuda  H,, Hayashi  K Y,, Matsushita  N.. Effects of baicalein isolated from roots of Scutellaria baicalensis Georgi on interleukin-1β and TNF-induced tissue-type plasminogen activator and plasminogen activator inhibitor-1 production in cultured human umbilical vein endothelial cells.  Phytotherapy Res.. 1997;;  11 363-7
• 116 Bereta  J,, Bereta  M,, Allison  A C,, Kruger  P B,, Koj  A.. Inhibitory effect of dicatechol rooperol on VCAM-1 and iNOS expression in cytokine-stimulated endothelium.  Life Sciences. 1996;;  60 325-34
• 117 Gille  J,, Paxton  L LL,, Lawley  T J,, Caughman  S W,, Swerlick  R A.. Retinoic acid inhibits the regulated expression of VCAM-1 by cultured dermal microvascular endothelial cell.  J. Clin. Invest.. 1997;;  99 492-500
• 118 Hisa  T,, Kimura  Y,, Takada  K,, Suzuki  F,, Takigawa  M.. Shikonin, an ingredient of Lithospermum erythrorhizon, inhibits angiogenesis in vivo and in vitro.  Anticancer Res.. 1998;;  18 783-90
• 119 Pendurthi  U R,, Williams  J T,, Rao  L VM.. Resveratrol, a polyphenolic compound found in wine, inhibits tissue factor expression in vascular cells - A possible mechanism for the cardiovascular benefits associated with moderate consumption of wine.  Arteriosclerosis, Thrombosis Vascular Biol.. 1999;;  19 419-26
• 120 Khalfoun  B,, Thibault  F,, Watier  H,, Bardos  P,, Lebrachu  Y.. Docosahexaenoic and eicosapentaenoic acids inhibit in vitro human endothelial cell production of interleukin-6.  Adv. Exp. Med. Biol.. 1997;;  400 589-97
• 121 Sato  M,, Miyazaki  T,, Kambe  F,, Maeda  K,, Seo  H.. Quercetin, a bioflavonoid, inhibits the induction of interleukin-8 and monocyte chemoattractant protein-1 expression by TNF in cultured human synovial cells.  J. Rheumatol.. 1997;;  24 1680-4
• 122 Katsuyama  K,, Shichiri  M,, Kato  H,, Imai  T,, Marumo  F,, Hirata  Y.. Differential inhibitory actions by glucocorticoid and aspirin on cytokine-induced nitric oxide production in vascular smooth muscle cells.  Endocrinology. 1999;;  140 2183-90
• 123 Chan  M MY,, Huang  H I,, Fenton  M R,, Fong  D.. In vitro inhibition of nitric oxide synthase gene expression by curcumin, a cancer preventive natural product with anti-inflammatory properties.  Biochem. Pharmacol.. 1998;;  55 1955-62
• 124 Jeyarajah  D R,, Kielar  M,, Penfield  J,, Lu  C Y.. Docosahexaenoic acid, a component of fish oil, inhibits nitric oxide production in vitro. .  J. Surg. Res.. 1999;;  83 147-50
• 125 Bereta  M,, Bereta  J,, Georgoff  I,, Coffman  F D,, Cohen  S,, Cohen  M C.. Methylxanthins and calcium-mobilizing agents inhibit the expression of cytokine-inducible nitric oxide synthase and vascular cell adhesion molecule-1 in murine microvascular endothelial cells.  Exp. Cell Res.. 1994;;  212 230-42
• 126 Fast  D J,, Lynch  R C,, Leu  R W.. Cyclosporin A inhibits nitric oxide production by L929 cells in response to TNF and interferon-γ.  J. Interferon Res.. 1993;;  13 235-40
• 127 Jeyarajah  D R,, Kielar  M,, Penfield  J,, Lu  C Y.. Docosahexaenoic acid, a compound of fish oil, inhibits nitric oxide production in vitro. .  J. Sug. Res.. 1999;;  83 147-50
• 128 Lu  C Y,, Penfield  J G,, KhairiDin  T A,, Sicher  S C,, Kielar  M L,, Vazquez  M A,, Che  L.. Docosahexaenoic acid, a constituent of fetal and neonatal serum, inhibits nitric oxide production by murine macrophages stimulated by IFN-γ plus LPS, or by IFN-γ plus Listeria monocytogenes. .  J. Reprod. Immunol.. 1998;;  38 31-53