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Molecular Mechanism Underlying Anti-Inflammatory and Anti-Allergic Activities of Phytochemicals: An Update

Yuva Bellik, Laïd Boukraâ, Hasan Alzahrani and 4 more

Molecules · 2012 · Review · CC BY

doi:10.3390/molecules18010322

Abstract

The resort worldwide to edible medicinal plants for medical care has increased significantly during the last few years. Currently, there is a renewed interest in the search for new phytochemicals that could be developed as useful anti-inflammatory and anti-allergic agents to reduce the risk of many diseases. The activation of nuclear transcription factor-kappa B (NF-κB) has now been linked to a variety of inflammatory diseases, while data from numerous studies underline the importance of phytochemicals in inhibiting the pathway that activates this transcription factor. Moreover, the incidence of type I allergic disorders has been increasing worldwide, particularly, the hypersensitivity to food. Thus, a good number of plant products with anti-inflammatory and anti-allergic activity have been documented, but very few of these compounds have reached clinical use and there is scant scientific evidence that could explain their mode of action. Therefore, this paper intends to review the most salient recent reports on the anti-inflammatory and anti-allergic properties of phytochemicals and the molecular mechanisms underlying these properties.

Full text

From PubMed Central, U.S. National Library of Medicine, as current on Oct 23, 2026. Paragraph numbers are ours, so an answer can point at one.

1. Introduction

Plants have been the basis of many traditional medicine systems throughout the World for thousands of years and still remain as the main new source of structurally important chemical substances that lead to the development of innovative drugs. The use of medicinal plants for the treatment of many diseases is associated with folk medicine from different parts of the World. Nowadays, the search for new anti-inflammatory and anti-allergic agents from the huge array of medicinal plant resources is intensifying. In fact, a variety of bioactive components have been shown to modulate inflammatory responses. The inflammatory response is a critical protective reaction to irritation, injury, or infection, characterised by redness, heat, swelling, loss of function and pain. Redness and heat result from an increase in blood flow, swelling is associated with increased vascular permeability, and pain is the consequence of activation and sensitisation of primary afferent nerve fibres.

The understanding of the cellular and molecular mechanisms involved in the inflammatory process has increased considerably in recent decades and this has permitted the discovery of many promising targets for the development of new drugs to treat chronic inflammatory diseases. A great number of inflammatory mediators including kinins, platelet-activating factor (PAF), prostaglandins, leukotrienes, amines, purines, cytokines, chemokines and adhesion molecules, has been found to act on specific targets, leading to the local release of other mediators from leukocytes and the further attraction of leukocytes, such as neutrophils, to the site of inflammation.

The constant advent of new findings from immunohistochemical, biochemical, molecular and functional animal models, together with clinical trials, has greatly increased the interest in the study of the mechanisms that underlie the inflammatory process. Recently, roles have been identified for several inflammatory cells and for a large number of inflammatory mediators in important pathologies not previously known to be linked to inflammation, such as Alzheimer’s disease and cardiovascular disorders including atherosclerosis, as well as cancer, reviewed in Akiyama et al. and Libby et al..

Natural products have long been, over the years, contributed to the development of modern therapeutic drugs. Evidence exists that drugs derived from natural products can modulate various inflammatory mediators (arachidonic acid metabolites, peptides, cytokines, excitatory amino acids, etc.), the production and/or action of second messengers (cGMP, cAMP, protein kinases, and calcium), the expression of transcription factors such as AP-1, NF-κB, and proto-oncogenes (c-jun, c-fos, and c-myc), and the expression of key pro-inflammatory molecules such as inducible NO synthase (iNOS), cyclooxygenase (COX-2), cytokines (IL-1β, TNF-α), neuropeptides and proteases.

In parallel, the allergic process has an important inflammatory component in which mast cell activation and degranulation are the first phenomena observed. During this process, mast cells release several inflammatory mediators including histamine (5-HT), platelet aggregating factor (PAF), leukotrienes, and a variety of cytokines. Hypersensitivity type I, an allergic reaction, is an IgE mediated immune response, resulting in histamine secretion from mast cells and blood basophils. The early phase reaction of allergy occurs within minutes after allergen exposure, whereas the late phase reaction occurs hours later and involves in cytokines secretion such as TNF-α and IL-4.

The discovery of drugs that can be used for the treatment of inflammatory and allergic diseases is important in human health. Drug discovery from plants involves a multidisciplinary approach combining botanical, ethnobotanical, phytochemical and biological techniques. Several natural product drugs of plant origin are in clinical use and some are undergoing Phase II and Phase III clinical trials. This review highlights the current patents about the potential benefits and effectiveness of phytochemicals that have shown experimental or clinical anti-inflammatory or anti-allergic activities, the possible mechanism of action and their therapeutic value.

2. Major Classes of Phytochemicals

Plants are rich in a wide variety of secondary metabolites, the great majority of which do not appear to participate directly in growth and development. Based on their biosynthetic origins, phytochemicals can be classified as carotenoids, phenolics, alkaloids, nitrogen-containing compounds, and organosulfur compounds. Interestingly, an important classification has been depicted by Liu gathering nearly most of dietary phytochemical classes and the structures of their main chemically relevant components (Figure 1).

Phytochemicals, although noted for the complexity of their chemical structures and biosynthetic pathways, they have been widely perceived as biologically insignificant and have historically received little attention from most plant biologists. Organic chemists, however, have long been interested in these novel phytochemicals and have investigated their chemical properties extensively since the 1850s. At present numerous studies have established that the phytochemical content of plants contributes to their protective effects against acute, chronic, and degenerative diseases.

3.1. Inflammation

Wide ranges of phytoconstituents were responsible for anti-inflammatory activity including phenolics, alkaloids, and terpenoids. However, efforts have focused on a class of compounds to elucidate the mechanisms of action of herbs, characterize and establish their potential utility as therapeutic agents in the treatment of inflammatory diseases.

Several mechanisms of action have been proposed to explain the anti-inflammatory actions of phytoconstituents, it consist broadly in: (1) Antioxidative and radical scavenging activities; (2) Modulation of cellular activities of inflammation-related cells (mast cells, macrophages, lymphocytes, and neutrophils); (3) Modulation of proinflammatory enzyme activities such as phospholipase A2 (PLA2), cyclooxygenase (COX), and lipoxygenase (LOX) and the nitric oxide (NO) producing enzyme, nitric oxide synthase (NOS); (4) Modulation of the production of other proinflammatory molecules; (5) Modulation of proinflammatory gene expression.

The Table 1 and Table 2 summarize the most studied and well-known phytochemicals including polyphenols (Figure 2), alkaloids (Figure 3), and terpenes (Figure 4) compounds with anti-inflammatory activities and their cellular and molecular mechanism. It should be noted that several other reports demonstrating the similar results are not represented here.

The inflammatory process can be initiated by various inflammatory stimuli including viruses, chemicals, and reactive oxygen/nitrogen species, which subsequently increases the synthesis and secretion of proinflammatory cytokines. Moreover, the unchecked activation of NF-κB/AP-1 and the production of TNF-α signaling have provided compelling evidence about the critical role for these factors in coupling inflammation and many chronic diseases. Phytochemicals have been shown to modulate various points in these inflammatory processes. These modulations serve as controlling points where the amplification of the inflammatory processes can be disconnected and thereby reduce subsequent diseases risk.

3.2. Allergy

The allergic process has an important inflammatory component. Hypersensitivity reactions can be divided into four types:

Type I: Called immediate or anaphylactic hypersensitivity mediated by IgE. Mast cells and basophils play a central role in immediate allergic inflammation through releasing chemical mediators such as histamine and cysteinyl leukotrienes, cytokines and chemokines. The reaction may involve skin (eczema), eyes (conjunctivitis), nasopharynx (rhinitis), bronchopulmonary tissues (asthma) and gastrointestinal tract (gastroenteritis).

Type II: Known as antibody-mdiated cytotoxicity mediated by antibodies of the IgM or IgG classes and complement. Antibodies directed against cell surface antigens causes cell damage such as hemolytic disease of the newborn (Rh disease) and myasthenia gravis (MG).

Type III: Known as immune complex hypersensitivity mediated by IgG or IgM classes. The reaction may be general (serum sickness) or may involve individual organs including skin (systemic lupus erythematosus), joints (rheumatoid arthritis) or other organs.

Type IV: Known as cell mediated or delayed type hypersensitivities. These reactions are mediated by CD4+T cells, and involved in the pathogenesis of many autoimmune diseases (multiple sclerosis). Another form of delayed hypersensitivity is contact dermatitis (poison ivy).

Therapeutic intervention in allergic disease has thus commonly focused on suppressing IgE production and blocking the action of histamine, thus regulating the expression and/or release of cytokines, chemokines, adhesion molecules, and or/inflammatory mediators. Below (Table 3 and Table 4) are summarized some of the most studied and well-known phytochemicals with anti-allergic effects and their mode of action. Here, too, several other reports demonstrating the similar results are not represented.

Despite the promising use of plant products for medicinal purposes for the evidences discussed above, it is worth noting that many of the dietary phytochemicals or natural products are not without cytotoxic effect and can originate various allergic reactions. The well known allergenic phytoconstituents are sesquiterpene lactones and furanocoumarins. Many of plants containing sesquiterpene lactones cause allergic contact dermatitis and effective treatments are scarce. Other natural products such as flavonoids, alkaloids, and terpenoids can also cause allergic reactions. Phenolics such as: anethol, atranorin, catechols, cinnamon, cinnamic derivatives, benzoic acid, curcumin, eugenol, isoeugenol, litreol, ginkgolic acid, resorcinols, oak moss resin, tertiaery-butylhydroquinone, urushiol, usnic acid. Alkaloids such as: atropine, pilocarpine, quinine, thebaine, codeine, and terpenoids such as: abietic acid, alantolactone, artesunate, asiaticoside, asiatic and madecassic acids, carvone, citral, β-cyclocostunolide, dehydroabietic acid, eucalyptol, farnesol, geraniol, limonene, α-pinene, phellandrene, linalool, menthol, myrrh, parthenolide, polygodial, sesquiterpenes, sesquiterpenes, thymol (reviewed in Rios et al.). While flavonoids are only weakly antigenic and usually do not induce immune reactions after consumption or therapeutic application, antibodies against flavonoids have been found in human blood. Adverse side effects of polyphenol intake on cardiovascular diseases have been also reported. A high consumption of polyphenol (2 g chlorogenic acid per day during 1 week) significantly increased homocysteinemia. The consumption of tea has been associated with a higher bone mineral density. A recent randomized crossover trial revealed that moderate consumption of red wine reduced erythrocyte superoxide dismutase activity. Another randomized double-blind, placebo-controlled trial showed that the combination of vitamin C and grape-seed polyphenols increases blood pressure.

4. Conclusions

Phytochemicals show both anti-inflammatory and anti-allergic activities in vitro and in vivo. Several cellular action mechanisms are proposed to explain their mode of action. Any single mechanism could not explain all of their in vivo activities. They probably have multiple cellular mechanisms acting on multiple sites of cellular machinery. The continual efforts will provide new insight into the anti-inflammatory and anti-allergic activities of phytochemicals, and eventually lead to development of a new class of anti-inflammatory and anti-allergic agents. However, the concern and difficulties related to the investigation of herbal medicines have precluded the financial incentives that could be provided to pharmaceutical industries. As a function of such difficulties, few herbal drugs have been studied adequately and well-controlled double-blind clinical trials to prove their safety and efficacy have been lacking. The trend today, especially in an industrial setting, is to seek bioactive compounds from plants that will serve as lead compounds for synthetic or semisynthetic development, and knowledge of the main pharmacologically active plant compounds is an essential requirement to standardize procedures for obtaining herbal remedies in order to replace crude products with modern pharmacological formulations.

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  61. 61.

    Landorfi R., Mower R.L., Steiner M. Modification of platelet function and arachidonic acid metabolism by biflavonoids. Structure-activity relations. Biochem. Pharmacol. 1984;33:1525-1530.

    Not in our library10.1016/0006-2952(84)90423-4

  62. 62.

    Akhtar N., Haqqi T.M. Epigallocatechin-3-gallate suppresses the global interleukin-1beta-induced inflammatory response in human chondrocytes. Arthritis Res. Ther. 2011;13:R93.

    Not in our library10.1186/ar3368

  63. 63.

    Kimura Y., Okuda H., Nomura T., Fukai T., Arichi S. Effects of phenolic constituents from the mulberry tree on arachidonate metabolism in rat platelets. J. Nat. Prod. 1986;49:639-644.

    Not in our library10.1021/np50046a013

  64. 64.

    Lin C.N., Lu C.M., Lin H.C., Fang S.C., Shieh B.J., Hsu M.F., Wang J.P., Ko F.N., Teng C.M. Novel antiplatelet constituents from Formosan Moraceous plants. J. Nat. Prod. 1996;59:834-838.

    Not in our library10.1021/np960376j

  65. 65.

    Gerhauser C., Klimo K., Heiss E., Neumann I., Gamal-Eldeen A., Knauft J., Liu G.Y., Sitthimonchai S., Frank N. Mechanism-based in vitro screening of potential cancer chemopreventive agents. Mutat. Res. 2003;523-524:163-172.

    Not in our library10.1016/s0027-5107(02)00332-9

  66. 66.

    Csaki C., Keshishzadeh N., Fischer K., Shakibaei M. Regulation of inflammation signaling by resveratrol in human chondrocytes in vitro. Biochem. Pharmacol. 2008;75:677-687.

    Not in our library10.1016/j.bcp.2007.09.014

  67. 67.

    Ferrandiz M.L., Ramachandran Nair A.G., Alcaraz M.J. Inhibition of sheep platelet arachidonatemetabolism by flavonoids from Spanish and Indian medicinal herbs. Pharmazie. 1990;45:206-208.

    Not in our library

  68. 68.

    You K.M., Jong H., Kim H.P. Inhibition of cyclooxygenase/lipoxygenase from human platelets by polyhydroxylated/methoxylated flavonoids isolated from the several medicinal plants. Arch. Pharm. Res. 1999;22:18-24.

    Not in our library10.1007/bf02976430

  69. 69.

    Chi Y.S., Jong H., Son K.H., Chang H.W., Kang S.S., Kim H.P. Effects of naturally occurring prenylated flavonoids on arachidonic acid metabolizing enzymes: Cylooxygenases and lipoxygenases. Biochem. Pharmacol. 2001;62:1185-1191.

    Not in our library10.1016/s0006-2952(01)00773-0

  70. 70.

    Moon T.C., Murakami M., Kudo I., Son K.H., Kim H.P., Kang S.S., Chang H.W. A new class of Cox-2 inhibitor, rutaecarpine from Evoida rutaecarpa. Inflamm. Res. 1999;48:621-625.

    Not in our library10.1007/s000110050512

  71. 71.

    Hou C.-C., Chen Y.-P., Wu J.-H., Huang C.-C., Wang S.-Y., Yang N.-S., Shyur L.-F. A Galactolipid possesses novel cancer chemopreventive effects by suppressing inflammatory mediators and mouse B16 melanoma. Cancer Res. 2007;67:6907-6915.

    Not in our library10.1158/0008-5472.can-07-0158

  72. 72.

    Noreen Y., Serrano G., Perera P., Bohlin L. Flavan-3-ols isolated from some medicinal plants inhibiting COX-1 and COX-2 catalysed prostaglandin biosynthesis. Planta Med. 1998;64:520-524.

    Not in our library10.1055/s-2006-957506

  73. 73.

    Jang D.S., Cuendet M., Hawthorne M.E. Prenylated flavonoids of the leaves of Macaranga conifera with inhibitory activity against cyclooxygenase-2. Phytochemistry. 2002;61:867-872.

    Not in our library10.1016/s0031-9422(02)00378-3

  74. 74.

    Likhiwitayawuid K., Sawasdee K., Kirtikara K. Flavonoids and stilbenoids with COX-1 and COX-2 inhibitory activity from Dracaena loureiri. Planta Med. 2002;68:841-843.

    Not in our library10.1055/s-2002-34403

  75. 75.

    Sailer E.R., Subramanian L.R., Rall B., Hoernlein R.F., Ammon H.P., Safayhi H. Acetyl-11-keto-beta-boswellic acid (AKBA): Structure requirements for binding and 5-lipoxygenase inhibitory activity. Br. J. Pharmcol. 1996;117:615-618.

    Not in our library10.1111/j.1476-5381.1996.tb15235.x

  76. 76.

    Safayhi H., Boden S.E., Schweizer S., Ammon H.P. Concentration-dependent potentiating and inhibitory effects of Boswellia extracts on 5-lipoxygenase product formation in stimulated PMNL. Planta Med. 2000;66:110-113.

    Not in our library10.1055/s-2000-11136

  77. 77.

    Prieto J.M., Giner R.M., Recio M.M.C., Schinella G., Manez S., Rios J.L. Diphyllin acetylapioside, a 5-lipoxygenase inhibitor from Haplophyllum hispanicum. Planta Med. 2002;68:359-360.

    Not in our library10.1055/s-2002-26747

  78. 78.

    Nakadate T., Yamamoto S., Aizu E., Kato R. Effects of flavonoids and antioxidants on 12-O-tetradecanoylphorbol 13-acetate induced epidermal ornithine decarboxylase induction and tumor promotion in relation to lipoxygenase inhibition by these compounds. Gann. 1984;75:214-222.

    Not in our library

  79. 79.

    Laughton M.J., Evans P.J., Moroney M.A., Hoult J.R.S., Halliwell B. Inhibition of mammalian 5-lipoxygenase and cyclooxygenase by flavonoids and phenolic dietary additives. Biochem. Pharmacol. 1991;42:1673-1681.

    Not in our library10.1016/0006-2952(91)90501-u

  80. 80.

    Kim H.P., Indu M., Iversen L., Ziboh V.A. Effects of naturally occurring flavonoids and biflavonoids on epidermal cyclooxygenase and lipoxygenase from guinea-pigs. Prostaglandins Leukot. Essent. Fatty Acids. 1998;58:17-24.

    Not in our library10.1016/s0952-3278(98)90125-9

  81. 81.

    Yoshimoto T., Furukawa M., Yamamoto S., Horie T., Watanabe-Kohno S. Flavonoids: Potent inhibitors of arachidonate 5-lipoxygenase. Biochem. Biophys. Res. Commun. 1983;116:612-618.

    Not in our library10.1016/0006-291x(83)90568-5

  82. 82.

    Reddy G.R., Ueda N., Hada T., Sackeyfio A.C., Yamamoto S., Hana Y. A prenylatedflavone, artonin E, as arachidonate 5-lipoxygenase inhibitor. Biochem. Pharmacol. 1991;41:115-118.

    Not in our library10.1016/0006-2952(91)90018-z

  83. 83.

    Kinaci M.K., Erkasap N., Kucuk A., Koken T., Tosun M. Effects of quercetin on apoptosis, NF-κB and NOS gene expression in renal ischemia/reperfusion injury. Exp. Ther. Med. 2012;3:249-254.

    Not in our library10.3892/etm.2011.382

  84. 84.

    Wang Y., Zhu Y., Gao L., Yin H., Xie Z., Wang D., Zhu Z., Han X. Formononetin attenuates IL-1β-induced apoptosis and NF-κB activation in INS-1 cells. Molecules. 2012;17:10052-10064.

    Not in our library10.3390/molecules170910052

  85. 85.

    Sadowska-Krowicka H., Mannick E.E., Oliver P.D., Sandoval M., Zhang X.J., Eloby-Childess S., Clark D.A., Miller M.J. Genistein and gut inflammation: Role of nitric oxide. Proc. Soc. Exp. Biol. Med. 1998;217:351-357.

    Not in our library10.3181/00379727-217-44244

  86. 86.

    Soliman K.F.A., Mazzio E.A. In vitro attenuation of nitric oxide production in C6 astrocyte cell culture by various dietary compounds. Proc. Soc. Exp. Biol. Med. 1998;218:390-397.

    Not in our library10.3181/00379727-218-44309

  87. 87.

    Kim H., Kim Y.S., Kim S.Y., Suk K. The plant flavonoid wogonin suppresses death of activated C6 rat glial cells by inhibiting nitric oxide production. Neurosci. Lett. 2001;309:67-71.

    Not in our library10.1016/s0304-3940(01)02028-6

  88. 88.

    Kao T.K., Ou Y.C., Raung S.L., Lai C.Y., Liao S.L., Chen C.J. Inhibition of nitric oxide production by quercetin in endotoxin/cytokine-stimulated microglia. Life Sci. 2010;86:315-321.

    Not in our library10.1016/j.lfs.2009.12.014

  89. 89.

    Fu P.K., Wu C.L., Tsai T.H., Hsieh C.L. Anti-Inflammatory and anticoagulative effects of paeonol on LPS-induced acute lung injury in rats. Evid. Based Complement. Alternat. Med. 2012.

    Not in our library10.1155/2012/837513

  90. 90.

    Geng Y., Zhang B., Lotz M. Protein tyrosine kinase activation is required for lipopolysaccharide induction of cytokines in human blood monocytes. J. Immunol. 1993;151:6692-6700.

    Not in our library

  91. 91.

    Yoon J.S., Chae M.K., Lee S.Y., Lee E.J. Anti-inflammatory effect of quercetin in a whole orbital tissue culture of Graves’ orbitopathy. Br. J. Ophthalmol. 2012;96:1117-1121.

    Not in our library10.1136/bjophthalmol-2012-301537

  92. 92.

    Jang S., Dilger R.N., Johnson R.W. Luteolin inhibits microglia and alters hippocampal-dependent spatial working memory in aged mice. J. Nutr. 2010;140:1892-1898.

    Not in our library10.3945/jn.110.123273

  93. 93.

    Lin N., Sato T., Takayama Y., Mimaki Y., Sashida Y., Yano M., Ito A. Novel anti-inflammatory actions of nobiletin, a citrus polymethoxy flavonoid, on human synovial fibroblasts and mouse macrophages. Biochem. Pharmacol. 2003;65:2065-2071.

    Not in our library10.1016/s0006-2952(03)00203-x

  94. 94.

    Krakauer T. The polyphenol chlorogenic acid inhibits staphylococcal exotoxin-induced inflammatory cytokines and chemokines. Immunopharmacol. Immunotoxicol. 2002;24:113-119.

    Not in our library10.1081/iph-120003407

  95. 95.

    Hong J.J., Jeong T.S., Choi J.H., Park J.H., Lee K.Y., Seo Y.J., Oh S.R., Oh G.T. Hematein inhibits tumor necrotic factor-alpha-induced vascular cell adhesion molecule-1 and NF-kappaB-dependent gene expression in human vascular endothelial cells. Biochem. Biophys. Res. Commun. 2001;281:1127-1133.

    Not in our library10.1006/bbrc.2001.4480

  96. 96.

    Jeong H.J., Koo H.N., Na H.J., Kim M.S., Hong S.H., Eom J.W., Kim K.S., Shin T.Y., Kim H.M. Inhibition of TNF-alpha and IL-6 production by Aucubin through blockade of NF-kappaB activation RBL-2H3 mast cells. Cytokine. 2002;18:252-259.

    Not in our library10.1006/cyto.2002.0894

  97. 97.

    An S.J., Pae H.O., Oh G.S., Choi B.M., Jeong S., Jang S.I., Oh H., Kwon T.O., Song C.E., Chung H.T. Inhibition of TNF-alpha, IL-1beta, and IL-6 productions and NF-kappa B activation in lipopolysaccharide-activated RAW 264.7 macrophages by catalposide, an iridoid glycoside isolated from Catalpa ovata G. Don (Bignoniaceae). Int. Immunopharmacol. 2002;2:1173-1181.

    Not in our library10.1016/s1567-5769(02)00085-1

  98. 98.

    Choi H.S., Kim H.S., Min K.R., Kim Y., Lim H.K., Chang Y.K., Chung M.W. Antiinflammatory effects of fangchinoline and tetrandrine. J. Ethnopharmacol. 2000;69:173-179.

    Not in our library10.1016/s0378-8741(99)00141-5

  99. 99.

    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-1 and tumor necrosis factor-alpha. Planta Med. 1995;61:497-501.

    Not in our library10.1055/s-2006-959356

  100. 100.

    Kiraz S., Ertenli I., Arici M., Calguneri M., Haznedaroglu I., Celik I., Pay S., Kirazli S. Effects of colchicine on inflammatory cytokines and selectins in familial Mediterranean fever. Clin. Exp. Rheumatol. 1998;16:721-724.

    Not in our library

  101. 101.

    Chiou W.F., Peng C.H., Chen C.F., Chou C.J. Anti-inflammatory propertiesof piperlactam S: Modulation of complement 5a-induced chemotaxis and inflammatory cytokines production in macrophages. Planta Med. 2003;69:9-14.

    Not in our library10.1055/s-2003-37041

  102. 102.

    Sun J., Han J., Zhao Y., Zhu Q., Hu J. Curcumin induces apoptosis in tumor necrosis factor-alpha-treated HaCaT cells. Int. Immunopharmacol. 2012;13:170-174.

    Not in our library10.1016/j.intimp.2012.03.025

  103. 103.

    Ding J., Polier G., Köhler R., Giaisi M., Krammer P.H., Li-Weber M. Wogonin and related natural flavones overcome tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) protein resistance of tumors by down-regulation of c-FLIP protein and up-regulation of TRAIL receptor 2 expression. J. Biol. Chem. 2012;2:641-649.

    Not in our library10.1074/jbc.m111.286526

  104. 104.

    Wadsworth T.L., McDonald T.L., Koop D.R. Effects of Ginkgo biloba extract (EGb 761) and quercetin on lipopolysaccharide-induced signaling pathways involved in the release of tumor necrosis factor-α. Biochem.Pharmacol. 2001;62:963-974.

    Not in our library10.1016/s0006-2952(01)00734-1

  105. 105.

    Morikawa K., Nonaka M., Narahara M., Torii I., Kawaguchi K., Yoshikawa T., Kumazawa Y., Morikawa S. Inhibitory effect of quercetin on carrageenan-induced inflammation in rats. Life Sci. 2003;74:709-721.

    Not in our library10.1016/j.lfs.2003.06.036

  106. 106.

    Dien M.V., Takahashi K., Mu M.M., Koide N., Sugiyama T., Mori I., Yoshida T., Yokochi T. Protective effect of wogonin on endotoxin-induced lethalshock in D-galactosamine-sensitized mice. Microbiol. Immunol. 2001;45:751-756.

    Not in our library10.1111/j.1348-0421.2001.tb01311.x

  107. 107.

    Takahashi K., Morikawa A., Kato Y., Sugiyama T., Koide N., Mu M.M., Yoshida T., Yokochi T. Flavonoids protect mice from two types of lethal shock induced by endotoxin. FEMS Immunol. Med. Microbiol. 2001;31:29-33.

    Not in our library10.1111/j.1574-695x.2001.tb01582.x

  108. 108.

    Shin D.K., Kim M.H., Lee S.H., Kim T.H., Kim S.Y. Inhibitory effects of luteolin on titanium particle-induced osteolysis in a mouse model. Acta Biomater. 2012;8:3524-3351.

    Not in our library10.1016/j.actbio.2012.05.002

  109. 109.

    Kim J.E., Son J.E., Jang Y.J., Lee D.E., Kang N.J., Jung S.K., Heo Y.S., Lee K., Lee H.J. Luteolin, a novel natural inhibitor of TPL2 kinase, inhibits tumor necrosis factor-α-induced cyclooxygenase-2 expression in JB6 mouse epidermis cell. J. Pharmacol. Exp. Ther. 2011;338:1013-1022.

    Not in our library10.1124/jpet.111.179200

  110. 110.

    Ueda H., Yamazaki C., Yamazaki M. A hydroxyl group of flavonoids affects oral anti-inflammatoryactivity and inhibition of systemic tumor necrosis factor-α production. Biosci. Biotechnol. Biochem. 2004;68:119-125.

    Not in our library10.1271/bbb.68.119

  111. 111.

    Li Y.C., Yeh C.H., Yang M.L., Kuan Y.H. Luteolin suppresses inflammatory mediator expression by blocking the Akt/NFκB pathway in acute lung injury induced by lipopolysaccharide in mice. Evid. Based Complement. Alternat. Med. 2012.

    Not in our library10.1155/2012/383608

  112. 112.

    Kumazawa Y., Kawaguchi K., Takimoto H. Immunomodulating effects of flavonoids on acute and chronic inflammatory responses caused by tumor necrosis factor α. Curr. Pharm. Des. 2006;12:4271-4279.

    Not in our library10.2174/138161206778743565

  113. 113.

    Okabe S., Suganuma M., Imayoshi Y., Taniguchi S., Yoshida T., Fujiki H. New TNFα releasing inhibitors, geraniin and corilagin, in leaves of Acer nikoense, Megusurino-Ki. Biol. Pharm. Bull. 2001;10:1145-1148.

    Not in our library10.1248/bpb.24.1145

  114. 114.

    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 tumor necrosis factor-alpha production in lipopolysaccharide-stimulated RAW264.7 cells. Arch. Pharmacol. Res. 1998;21:12-16.

    Not in our library10.1007/bf03216746

  115. 115.

    Cho J.Y., Baik K.U., Yoo E.S., Yoshikawa K., Park M.H. In vitro anti-inflammatory effects of neolignan woorenosides from the rhizomes of Coptis japonica. J. Nat. Prod. 2000;63:1205-1209.

    Not in our library10.1021/np9902791

  116. 116.

    Hart P.H., Brand C., Carson C.F., Riley T.V., Prager R.H., Finlay-Jones J.J. Terpinen-4-ol, themain component of the essential oil of Malaleuca alternifolia (tea tree oil), suppresses inflammatory mediator production by activated human monocytes. Inflamm. Res. 2000;49:619-626.

    Not in our library10.1007/s000110050639

  117. 117.

    Soares M.B., Bellintani M.C., Ribeiro I.M., Tomassini T.C., Ribeiro dos Santos R. Inhibition of macrophage activation and lipopolysaccaride-induced death by seco-steroids purified from Physalis angulata L. Eur. J. Pharmacol. 2003;459:107-112.

    Not in our library10.1016/s0014-2999(02)02829-7

  118. 118.

    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;44:193-2200.

    Not in our library10.1002/1529-0131(200109)44:9<2193::aid-art373>3.0.co;2-5

  119. 119.

    Liacini A., Sylvester J., Zafarullah M. Triptolide suppresses proinflammatory cytokine-induced matrix metalloproteinase and aggrecanase-1 gene expression in chondrocytes. Biochem. Biophys. Res. Commun. 2005;327:320-327.

    Not in our library10.1016/j.bbrc.2004.12.020

  120. 120.

    Ha S.K., Moon E., Ju M.S., Kim D.H., Ryu J.H., Oh M.S., Kim S.Y. 6-Shogaol, a ginger product, modulates neuroinflammation: A new approach to neuroprotection. Neuropharmacology. 2012;63:211-223.

    Not in our library10.1016/j.neuropharm.2012.03.016

  121. 121.

    Shany S., Levy Y., Lahav-Cohen M. The effects of 1α, 24(S)-dihydroxyvitamin D2 analog on cancer cell proliferation and cytokine expression. Steroids. 2001;66:319-325.

    Not in our library10.1016/s0039-128x(00)00154-9

  122. 122.

    Ono M., Tanaka N., Moriyasu T. Anti-inflammatory action of cepharanthine ointment ingredient in experimental animals: Studies on chronic inflammation and TNF-alpha production. Ensho. 1994;14:425-429.

    Not in our library10.2492/jsir1981.14.425

  123. 123.

    Parmely M.J., Zhou W.W., Edwards C.K., Borcherding D.R., Silverstein R., Morrison D.C. Adenosine and a related carbocyclic nucleoside analogue selectively inhibit tumor necrosis factor-alpha production and protect mice against endotox challenge. J. Immunol. 1993;151:389-396.

    Not in our library

  124. 124.

    Gerritsen M.E., Carley W.W., Ranges G.E., Shen C.P., Phan S.A., Ligon G.F., Perry C.A. Flavonoids inhibit cytokine-induced endothelial cell adhesion protein gene expression. Am. J. Pathol. 1995;147:278-292.

    Not in our library

  125. 125.

    Nakamura N., Hayasaka S., Zhang X.Y., Nagaki Y., Matsumoto M., Hayasaka Y., Terasawa K. Effects of baicalin, baicalein and wogonin on interleukin-6 and interleukin-8 expression, and nuclear factor-κB binding activities induced by interleukin-1β in human retinal pigmant epithelial cell line. Exp. Eye Res. 2003;77:195-202.

    Not in our library10.1016/s0014-4835(03)00116-7

  126. 126.

    Atluru D., Jackson T.M., Atluru S. Genistein, a selective protein tyrosine kinase inhibitor, inhibits interleukin-2 and leukotriene B4 production from human mononuclear cells. Clin. Immunol. Immunopathol. 1991;59:379-387.

    Not in our library10.1016/0090-1229(91)90033-7

  127. 127.

    Hernandez V., del Carmen Recio M., Manez S., Prieto J.M., Giner R.M., Rios J.L. A mechanistic approach to the in vivo anti-inflammatory activity of sesquiterpenoid compounds isolated from Inula viscosa. Planta Med. 2001;67:726-731.

    Not in our library10.1055/s-2001-18342

  128. 128.

    Danz H., Stoyanova S., Thomet O.A., Simon H.U., Dannhardt G., Ulbrich H., Hamburger M. Inhibitory activity of tryptanthrin on prostaglandin and leukotriene synthesis. Planta Med. 2002;68:875-880.

    Not in our library10.1055/s-2002-34922

  129. 129.

    Bermejo B.P., Abad Martinez M.J., Silvan Sen A.M., Sanz Gomez A., Fernandez Matellano L., Sanchez Contreras S., Diaz Lanza A.M. In vivo and in vitro anti-inflammatory activity of saikosaponins. Life Sci. 1998;63:1147-1156.

    Not in our library10.1016/s0024-3205(98)00376-2

  130. 130.

    Bermejo B.P., Diaz Lanza A.M., Silvan Sen A.M., de Santos Galindez J., Fernandez Matellano L., Sanz Gomez A., Abad Martinez M.J. Effects of some iridoids from plant origin on arachidonic acid metabolism in cellular systems. Planta Med. 2000;66:324-328.

    Not in our library10.1055/s-2000-8549

  131. 131.

    Giner-Larza E.M., Manez S., Giner R.M., Recio M.C., Prieto J.M., Cerda-Nicolas M., Rios J.L. Anti-inflammatory triterpenes from Pistacia terebinthus galls. Planta Med. 2002;68:311-315.

    Not in our library10.1055/s-2002-26749

  132. 132.

    Diaz Lanza A.M., Abad Martinez M.J., Fernandez Matellano L., Recuero Carretero C., Villaescusa Castillo L., Silvan Sen A.M., Bermejo Benito P. Lignan and phenylpropanoid glycosides from Phillyrea latifolia and their in vitro anti-inflammatory activity. Planta Med. 2001;67:219-223.

    Not in our library10.1055/s-2001-12004

  133. 133.

    Kim Y.P., Yamada M., Lim S.S., Lee S.H., Ryu N., Shin K.H. Inhibition of tectorigenin and tectoridin of prostaglandin E2 production and cyclooxygenase-2 induction in rat peritoneal macrophages. Biochim. Biophys. Acta. 1999;1438:399-407.

    Not in our library10.1016/s1388-1981(99)00067-0

  134. 134.

    Kim Y.P., Lee E.B., Kim S.Y., Li D., Ban H.S., Lim S.S., Shin K.H., Ohuchi K. Inhibition of prostaglandin E2 production by platycodin D isolated from the root of Platycodon grandiflorum. Planta Med. 2001;67:362-364.

    Not in our library10.1055/s-2001-14317

  135. 135.

    Hong C.H., Noh M.S., Lee W.Y., Lee S.K. Inhibitory effects of natural sesquiterpenoids isolated from the rhizomes of Curcuma zedoaria on prostaglandin E2 and nitric oxide production. Planta Med. 2002;68:545-547.

    Not in our library10.1055/s-2002-32560

  136. 136.

    Woo H.G., Lee C.H., Noh M.S., Lee J.J., Jung Y.S., Baik E.J., Moon C.H., Lee S.H. Rutaecarpine, a quinazolinocarboline alkaloid, inhibits prostaglandin production in RAW26.7 macrophages. Planta Med. 2001;67:505-509.

    Not in our library10.1055/s-2001-16479

  137. 137.

    Nakajima T., Imanishi M., Yamamoto K., Cyong J.C., Hirai K. Inhibitory effect of baicalein, a flavonoid in Scutellaria root, on eotaxin production by human dermal fibroblasts. Planta Med. 2001;67:132-135.

    Not in our library10.1055/s-2001-11532

  138. 138.

    Chi Y.S., Cheon B.S., Kim H.P. Effect of wogonin, a plant flavones from Scutellaria radix, on the suppression of cyclooxygenase and the induction of inducible nitric oxide synthase in lipopolysaccharide-treated RAW 26.7 cells. Biochem. Pharmacol. 2001;61:1195-1203.

    Not in our library10.1016/s0006-2952(01)00597-4

  139. 139.

    Kim H.K., Cheon B.S., Kim Y.H., Kim S.Y., Kim H.P. Effects of naturally occurring flavonoids on nitric oxide production in the macrophage cell line RAW 264.7 and their structural-activity relationships. Biochem. Pharmacol. 1999;58:759-765.

    Not in our library10.1016/s0006-2952(99)00160-4

  140. 140.

    Liang Y.C., Huang Y.T., Tsai S.H., Lin-Shiau S.Y., Chen C.F., Lin J.K. Suppression of inducible cyclooxygenase and inducible nitricoxide synthase by apigenin and related flavonoids in mousemacrophages. Carcinogenesis. 1999;20:1945-1952.

    Not in our library10.1093/carcin/20.10.1945

  141. 141.

    Murakami A., Nakamura Y., Torikai K., Tanaka T., Koshiba T., Koshimizu K., Kuwahara S., Takahashi Y., Ogawa K., Yano M., Tokuda H., et al. Inhibitory effect of citrus nobiletin onphorbol ester-induced skin inflammation, oxidative stress, and tumor promotion in mice. Cancer Res. 2000;60:5059-5066.

    Not in our library

  142. 142.

    Chen Y.C., Yang L.L., Lee T.J.F. Oroxylin A inhibition of lipopolysaccharide-induced iNOS and COX-2 gene expression via suppression of nuclear factor-κB activation. Biochem. Pharmacol. 2000;59:1445-1457.

    Not in our library10.1016/s0006-2952(00)00255-0

  143. 143.

    Raso G.M., Meli R., di Carlo G., Pacillio M., di Carlo R. Inhibiton of inducible nitric oxide synthase and cyclooxygenase-2 expression by flavonoids in macrophage J774A.1. Life Sci. 2001;68:921-931.

    Not in our library10.1016/s0024-3205(00)00999-1

  144. 144.

    Shen S.C., Lee W.R., Lin H.Y., Huang H.C., Ko C.H., Yang L.L., Chen Y.C. In vitro and in vivo inhibitory activities of rutin, wogonin, andquercetin on lipopolysaccharide-induced nitric oxide andprostaglandin E2 production. Eur. J. Pharmacol. 2002;446:187-194.

    Not in our library10.1016/s0014-2999(02)01792-2

  145. 145.

    Singh R., Ahmed S., Islam N., Goldberg V.M., Haqqi T.M. Epigallocatechin-3-gallate inhibits interleukin-1β-induced expression of nitric oxide synthase and production of nitric oxide in human chondrocytes. Suppression of nuclear factor κB by degradation of the inhibitor of nuclear factor κB. J. Rheumatol. 2002;46:2079-2086.

    Not in our library10.1002/art.10443

  146. 146.

    Chan M.M., Fong D., Ho C.T., Huang H.T. Inhibition of induciblenitric oxide synthase gene expression and enzyme activity byepigallocatechin gallate, a natural product from green tea. Biochem. Pharmacol. 1997;54:1281-1286.

    Not in our library10.1016/s0006-2952(97)00504-2

  147. 147.

    Takahashi T., Takasuka N., Ligo M., Baba M., Nishino H., Tsuda H. Isoliquilitigenin, a flavonoid from licorice, reduces prostaglandin E2 and nitric oxide, causes apoptosis, and suppresses aberrant crypt foci development. Cancer Sci. 2004;95:448-453.

    Not in our library10.1111/j.1349-7006.2004.tb03230.x

  148. 148.

    Kang J.S., Jeon Y.J., Kim H.M., Han S.H., Yang K.H. Inhibition of inducible nitric-oxide synthase expression by silymarin in lipopolysaccharide-stimulated macrophages. J. Pharmacol. Exp. Ther. 2002;302:138-144.

    Not in our library10.1124/jpet.302.1.138

  149. 149.

    Chan M.M., Huang H.I., Fenton M.R., Fong D. In vivo inhibition of nitric oxide synthase gene expression by curcumin, a cancer preventive natural product with anti-inflammatory properties. Biochem. Pharmacol. 1998;55:1955-1962.

    Not in our library10.1016/s0006-2952(98)00114-2

  150. 150.
    Anti-Inflammatory Effects of Flavonoids: Genistein, Kaempferol, Quercetin, and Daidzein Inhibit STAT-1 and NF- κ B Activations, Whereas Flavone, Isorhamnetin, Naringenin, and Pelargonidin Inhibit only NF- κ B Activation along with Their Inhibitory Effect on iNOS Expression and NO Production in Activated Macrophages · 2007
    No notice
  151. 151.

    Lee H., Kim Y.O., Kim H., Kim S.Y., Noh H.S., Kang S.S. Flavonoid wogonin from medicinal herb is neuroprotective by inhibiting inflammatory activation of microglia. FASEB J. 2003;17:1943-1944.

    Not in our library10.1096/fj.03-0057fje

  152. 152.

    Qureshi A.A., Guan X.Q., Reis J.C., Papasian C.J., Jabre S., Morrison D.C., Qureshi N. Inhibition of nitric oxide and inflammatory cytokines in LPS-stimulated murine macrophages by resveratrol, a potent proteasome inhibitor. Lipids Health Dis. 2012;11:76.

    Not in our library10.1186/1476-511x-11-76

  153. 153.

    Wang B., Ma L., Tao X., Lipsky P.E. Triptolide, an active component of the Chinese herbal remedy Tripterygium wilfordii Hook F, inhibits production of nitric oxide by decreasing inducible nitric oxide synthase gene transcription. Arthritis Rheum. 2004;50:2995-3003.

    Not in our library10.1002/art.20459

  154. 154.

    Suh N., Honda T., Finlay H.J., Barchowsky A., Williams C., Benoit N.E., Xie Q.W., Nathan C., Gribble G.W., Sporn M.B. Novel triterpenoids suppress inducible nitric oxide synthase (iNOS) and inducible cyclooxygenase (COX-2) in mouse macrophages. Cancer Res. 1998;58:717-723.

    Not in our library

  155. 155.

    Stempelj M., Kedinger M., Augenlicht L., Klampfer L. Essential role of the JAK/STAT1 signalingpathway in the expression of inducible and its regulation by butyrate. J. Biol. Chem. 2007;282:9797-804.

    Not in our library10.1074/jbc.m609426200

  156. 156.

    Palombo P., Fabrizi G., Ruocco V. Beneficial long-term effects of combined oral/topical antioxidanttreatment with the carotenoids lutein and zeaxanthin on humanskin: A double-blind, placebo-controlled study. Skin Pharmacol. Physiol. 2007;20:199-210.

    Not in our library10.1159/000101807

  157. 157.

    Kang N.J., Shin S.H., Lee H.J., Lee K.W. Polyphenols as small molecular inhibitors of signaling cascades in carcinogenesis. Pharmacol. Ther. 2011;130:310-324.

    Not in our library10.1016/j.pharmthera.2011.02.004

  158. 158.

    Hooshmand S., Soung do Y., Lucas E.A., Madihally S.V., Levenson C.W., Arjmandi B.H. Genistein reduces the production of proinflammatory molecules in human chondrocytes. J. Nutr. Biochem. 2007;18:609-614.

    Not in our library10.1016/j.jnutbio.2006.11.006

  159. 159.

    Kwak W.J., Han C.K., Son K.H., Chang H.W., Kang S.S., Park B.K., Kim H.P. Effects of ginkgetin from Ginkgo biloba leaves on cyclooxygenases and in vivo skin inflammation. Planta Med. 2002;68:316-321.

    Not in our library10.1055/s-2002-26742

  160. 160.

    Mutoh M., Takahashi M., Fukuda K., Komatsu H., Enya T., Matsushima-Hibiya Y., Mutoh H., Sugimura T., Wakabayashi K. Suppression by flavonoids of cyclooxygenase-2 promotor-dependent transcriptional activity incolon cancer cells: Structural-activity relationship. Jpn. J. Cancer Res. 2000;91:686-691.

    Not in our library10.1111/j.1349-7006.2000.tb01000.x

  161. 161.

    Chen C.Y., Peng W.H., Tsai K.D., Hsu S.L. Luteolin suppresses inflammation-associated gene expression by blocking NF-kappaB and AP-1 activation pathway in mouse alveolar macrophages. Life Sci. 2007;81:1602-1614.

    Not in our library10.1016/j.lfs.2007.09.028

  162. 162.

    Wakabayashi I., Yasui K. Wogonin inhibits inducible prostaglandin E2 production in macrophages. Eur. J. Pharmacol. 2000;406:477-481.

    Not in our library10.1016/s0014-2999(00)00695-6

  163. 163.

    Park B.K., Heo M.Y., Park H., Kim H.P. Inhibition of TPA-inducedcyclooxygenase-2 and skin inflammation in mice by wogonin, a plant flavone from Scutellaria radix. Eur. J. Pharmacol. 2001;425:153-157.

    Not in our library10.1016/s0014-2999(01)01187-6

  164. 164.

    Banerjee T., Valacchi G., Ziboh V.A., van der Vliet A. Inhibitionof TNFα-induced cyclooxygenase-2 expression by amentoflavonethrough suppression of NF-κB activation in A549 cells. Mol. Cell. Biochem. 2002;238:105-110.

    Not in our library10.1023/a:1019963222510

  165. 165.

    Tong X., Yin L., Joshi S., Rosenberg D.W., Giardina C. Cyclooxygenase-2 regulation in colon cancer cells: Modulation of RNA polymerase II elongation by histone deacetylase inhibitors. J. Biol. Chem. 2005;280:15503-15509.

    Not in our library10.1074/jbc.m411978200

  166. 166.

    Subbaramaiah K., Michaluart P., Sporn M.B., Dannenberg A.J. Ursolic acid inhibits cyclooxygenase-2 transcription in human mammary epithelial cells. Cancer Res. 2000;60:2399-2404.

    Not in our library

  167. 167.

    Suksamrarn A., Kumpun S., Kirtikara K., Yingyongnarongkul B., Suksamrarn S. Iridoids with anti-inflammatory activity from Vitex peduncularis. Planta Med. 2002;68:72-73.

    Not in our library10.1055/s-2002-20048

  168. 168.

    Hirata A., Murakami Y., Atsumi T., Shoji M., Ogiwara T., Shibuya K., Ito S., Yokoe I., Fujisawa S. Ferulic acid dimer inhibits lipopolysaccharide-stimulated cyclooxygenase-2 expression in macrophages. In Vivo. 2005;19:849-853.

    Not in our library

  169. 169.

    Kim S.O., Kundu J.K., Shin Y.K., Park J.H., Cho M.H., Kim T.Y., Surh Y.J. [6]-Gingerol inhibits COX-2 expression by blocking the activation of p38 MAP kinase and NF-κB in phorbol ester stimulated mouse skin. Oncogene. 2005;24:2558-2567.

    Not in our library10.1038/sj.onc.1208446

  170. 170.

    Kim J.K., Kim Y., Na K.M., Surh Y.J., Kim T.Y. [6]-Gingerol prevents UVB-induced ROS production and COX-2 expression in vitro and in vivo. Free Radic. Res. 2007;41:603-614.

    Not in our library10.1080/10715760701209896

  171. 171.

    Kundu J.K., Shin Y.K., Kim S.H., Surh Y.J. Resveratrol inhibits phorbol ester-induced expression of COX-2 and activation of NF-κB in mouse skin by blocking IκB kinase activity. Carcinogenesis. 2006;27:1465-1474.

    Not in our library10.1093/carcin/bgi349

  172. 172.

    Peng G., Dixon D.A., Muga S.J., Smith T.J., Wargovich M.J. Green tea polyphenol (−)-epigallocatechin-3-gallate inhibits cyclooxygenase-2 expression in colon carcinogenesis. Mol. Carcinog. 2006;45:309-319.

    Not in our library10.1002/mc.20166

  173. 173.

    Donnelly L.E., Newton R., Kennedy G.E., Fenwick P.S., Leung R.H.F., Ito K., Russell R.E.K., Barnes P.J. Anti-inflammatory effects of resveratrol in lung epithelial cells: Molecular mechanisms. Am. J. Physiol. Lung Cell. Mol. Physiol. 2004;287:L774-L783.

    Not in our library10.1152/ajplung.00110.2004

  174. 174.

    Haridas V., Arntzen C.J., Gutterman J.U. Avicins, a family of triterpenoid saponins from Acacia victoriae (Bentham), inhibit activation of nuclear factor-kappaB by inhibiting both its nuclear localization and ability to bind DNA. Proc. Natl. Acad. Sci.USA. 2001;98:11557-11562.

    Not in our library10.1073/pnas.191363498

  175. 175.

    Sheehan M., Wong H.R., Hake P.W., Malhotra V., O’Connor M., Zingarelli B. Parthenolide, an inhibitor of the nuclear factor-kappaB pathway, ameliorates cardiovascular derangement and outcome in endotoxicshock in rodents. Mol. Pharmacol. 2002;61:953-963.

    Not in our library10.1124/mol.61.5.953

  176. 176.

    Feng R., Lu Y., Bowman L.L., Qian Y., Castranova V., Ding M. Inhibition of AP-1, NF-kB and MAPKs and induction of phase 2 detoxifying enzyme activity by chlorogenic acid. J. Biol. Chem. 2005;280:2888-2895.

    Not in our library10.1074/jbc.m503347200

  177. 177.

    Qiu D., Zhao G., Aoki Y., Shi L., Uyei A., Nazarian S., Ng J.C.-H., Kao P.N. Immunosuppressant PG490(triptolide) inhibits T-cell interleukin-2 expression at the levelof purine-box/nuclear factor of activated T-cells and NFkappaB transcriptional activation. J. Biol. Chem. 1999;274:13443-13450.

    Not in our library10.1074/jbc.274.19.13443

  178. 178.

    Han S.S., Keum Y.S., Chun K.S., Surh Y.J. Suppression of phorbol ester-induced NF-jB activation by capsaicin in cultured human promyelocytic leukemia cells. Arch. Pharm. Res. 2002;25:475-479.

    Not in our library10.1007/bf02976605

  179. 179.

    Lührs H., Gerke T., Müller J.G., Melcher R., Schauber J., Boxberge F., Scheppach W., Menzel T. Butyrate inhibitsNF-κB activation in lamina propria macrophagesof patients with ulcerative colitis. Scand. J. Gastroenterol. 2002;37:458-466.

    Not in our library10.1080/003655202317316105

  180. 180.

    Kim J.S., Jobin C. The flavonoid luteolin prevents lipopolysaccharide-induced NK-kappaB signaling and gene expressionby blocking I-kappaB kinase activity in intestinal epithelial cellsand bone-marrow derived dendritic cells. Immunology. 2005;115:373-387.

    Not in our library10.1111/j.1365-2567.2005.02156.x

  181. 181.

    Jobin C., Bradham C.A., Russo M.P., Juma B., Narula A.S., Brenner D.A., Sartor R.B. Curcumin blocks cytokine-mediated NF-κB activation and pro-inflammatory gene expression by inhibiting inhibitory factor I-κB kinase activity. J. Immunol. 1999;163:3474-3483.

    Not in our library

  182. 182.

    Hunter M.S., Corley D.G., Carron C.P., Rowold E., Kilpatrick B.F., Durley R.C. Four new clerodane diterpenes from the leaves of Casearia guianensis which inhibit the interaction of leukocyte function antigen 1 with intercellular adhesion molecule 1. J. Nat. Prod. 1997;60:894-899.

    Not in our library10.1021/np970141n

  183. 183.

    Asahina A., Tada Y., Nakamura K., Tamaki K. Colchicine and griseofulvin inhibit VCAM-1 expression on human vascular endothelial cells-evidence for the association of VCAM-1 expression with microtubules. J. Dermatol. Sci. 2001;25:1-9.

    Not in our library10.1016/s0923-1811(00)00097-9

  184. 184.

    Goel A., Kunnumakkara A.B., Aggarwal B.B. Curcumin as “Curecumin”: From kitchen to clinic. Biochem. Pharmacol. 2008;75:787-809.

    Not in our library10.1016/j.bcp.2007.08.016

  185. 185.

    Kwak W.J., Cho Y.B., Han C.K., Shin H.J., Ryu K.H., Yoo H., Rhee H.I. Extraction and purification method of active constituents from stem of Lonicera japonica thunb, its usage for anti-inflammatory and analgesic drug. 2008.

    Not in our library

  186. 186.

    Kealey K.S., Snyder R.M., Romanczyk L.J., Geyet H.M., Myers M.E., Whitacre E.J., Schmitz H.H. Treatment of inflammation. 2008.

    Not in our library

  187. 187.

    Olalde Rangel J.A. Arthritis phyto-nutraceutical synergistic composition. 2008.

    Not in our library

  188. 188.

    Gokaraju G.R., Gokaraju R.R., Gottumukkala V.S., Golakoti T. Dietary supplement formulation for controlling inflammation and cancer. 2008.

    Not in our library

  189. 189.

    Gokaraju G.R., Gokaraju R.R., Gottumukkala V.S., Somepalli V. Pharmaceutically Active Extracts of Vitex Leucoxylon, a Process of Extracting the Same and a Method of Treating Diabetes and Inflammatory Diseases Therewith. 2008.

    Not in our library

  190. 190.

    Lockwood S.F., Mason P.R. Use of carotenoids and/or carotenoid derivatives/analogs for reduction/inhibition of certain negative effects of COX inhibitors. 2008.

    Not in our library

  191. 191.

    Li Y. Herbal compositions for prevention and treatment of rheumatic and inflammatory diseases and method of preparing the same. 2009.

    Not in our library

  192. 192.

    Buchholz H., Wirth C., Carola C., Alves Fontes R. Flavonoid derivates. 2009.

    Not in our library

  193. 193.

    Miyake Y., Yoko I. Anti-inflammatory agent. 2010.

    Not in our library

  194. 194.

    Gokaraju G.R., Gokaraju R.R., Golakoti T., Chirravuri V.R., Alluri V.K.R., Bhupathiraju K. Use of Aphanamixis polystacha extracts or fractions against 5-lipoxygenase mediated diseases. 2010.

    Not in our library

  195. 195.

    Hillwig M.L. Anti-inflammatory and anti-HIV compositions and methods of use. 2010.

    Not in our library

  196. 196.

    Theoharides T.C. Anti-inflammatory compositions for treating multiple sclerosis. 2011.

    Not in our library

  197. 197.

    Mumper R.J., Dai J., Gallicchio V.S. Berry preparations and extracts. 2011.

    Not in our library

  198. 198.

    Jia Q., Nichols T.C., Rhoden E.E., Walte S. Identification of Free-B-Ring flavonoids as potent COX-2 inhibitors. 2011.

    Not in our library

  199. 199.

    Kimata M., Shichijo M., Miura T., Serizawa I., Inagaki N., Nagai H. Effects of luteolin, quercetin and baicalein on immunoglobulin E-mediated mediator release from human cultured mast cells. Clin. Exp. Allergy. 2000;30:501-508.

    Not in our library10.1046/j.1365-2222.2000.00768.x

  200. 200.

    Yano S., Tachibana H., Yamada K. Flavones suppress the expression of the high-affinity IgE receptor Fc epsilon RI in human basophilic KU812 cells. J. Agric. Food Chem. 2005;53:1812-1817.

    Not in our library10.1021/jf047929d

  201. 201.

    Wu S.J., Ng L.T. Tetrandrine inhibits proinflammatory cytokines, iNOS and COX-2 expression in human monocytic cells. Biol. Pharm. Bull. 2007;30:59-62.

    Not in our library10.1248/bpb.30.59

  202. 202.

    Otsuka H., Hirai Y., Nagao T., Yamasaki K. Antiinflammatory activity of benzoxazinoids from roots of Coix lachryma-jobi var. ma-yuen. J. Nat. Prod. 1988;51:74-79.

    Not in our library10.1021/np50055a009

  203. 203.

    Wang M., Huang Y.J., Zhang T.H., Tong Z.Q. Anti-allergic, anti-histamine and anti-inflammatory effects ofcompound pseudoephedrine. J. Shenyang Pharm. Univ. 1996;132:129-133.

    Not in our library

  204. 204.

    Daikonya A., Katsuki S., Wu J.-B., Kitanaka S. Anti-allergic agents from natural sources (41)): Anti-allergic activity of new phloroglucinol derivatives from Mallotus philippensis (Euphorbiaceae). Chem. Pharm. Bull. 2002;50:1566-1659.

    Not in our library10.1248/cpb.50.1566

  205. 205.

    Cheong H., Ryu S.Y., Oak M.H., Cheon S.H., Yoo G.S., Kim K.M. Studies of structure activity relationship of flavonoids for the anti-allergic actions. Arch. Pharm. Res. 1998;21:478-480.

    Not in our library10.1007/bf02974647

  206. 206.

    Fewtrell C.M., Gomperts B.D. Effect of flavone inhibitors on transport ATPases on histamine secretion from rat mast cells. Nature. 1977;265:635-636.

    Not in our library10.1038/265635a0

  207. 207.

    Middleton E.J., Drzewiecki G., Krishnarao D. Quercetin: An inhibitor of antigen-induced human basophil histamine release. J. Immunol. 1981;127:546-550.

    Not in our library

  208. 208.

    Fernandez J., Reyes R., Ponce H., Oropeza M., Vancalsteren M.R., Jankowski C., Campos M.G. Isoquercitrin from Argemone platyceras inhibits carbachol and leukotriene D4-induced contraction in guinea-pig airways. Eur.J. Pharmacol. 2005;522:108-115.

    Not in our library10.1016/j.ejphar.2005.08.046

  209. 209.

    Kawai M., Hirano T., Higa S., Arimitsu J., Maruta M., Kuwahara Y., Ohkawara T., Hagihara K., Yamadori T., Shima Y., et al. Flavonoids and related compounds as anti-allergic substances. Allergol. Int. 2007;56:113-123.

    Not in our library10.2332/allergolint.r-06-135

  210. 210.

    Hirano T., Arimitsu J., Higa S., Naka T., Ogata A., Shima Y., Fujimoto M., Yamadori T, Ohkawara T., Kuwabara Y., et al. Luteolin, a flavonoid, inhibits CD40 ligand expression by activated human basophils. Int. Arch. Allergy Immunol. 2006;140:150-156.

    Not in our library10.1159/000092554

  211. 211.

    Wu Y.Q., Zhou C.H., Tao J., Li S.N. Antagonistic effects of nobiletin, a polymethoxyflavonoid, on eosinophilic airway inflammation of asthmatic rats and relevant mechanisms. Life Sci. 2006;78:2689-2696.

    Not in our library10.1016/j.lfs.2005.10.029

  212. 212.

    Magrone T., Jirillo E. Influence of polyphenols on allergic immune reactions: Mechanisms of action. Proc. Nutr. Soc. 2012;71:316-321.

    Not in our library10.1017/s0029665112000109

  213. 213.

    Joskova M., Franova S., Sadloňova V. Acute bronchodilator effect of quercetin in experimental allergic asthma. Bratisl. Lek. Listy. 2011;112:9-12.

    Not in our library

  214. 214.

    Fraňova S., Strapkova A., Mokry J., Šutovska M., Joškova M., Sadloňova V., Antošova M., Pavelčikova D., Fleškova D., Nosaľova G. Pharmacologic modulation of experimentally induced allergic asthma. Interdiscp. Toxicol. 2011;4:27-32.

    Not in our library10.2478/v10102-011-0006-x

  215. 215.

    Joskova M., Sadlonova V., Nosalova G., Novakova E., Franova S. Polyphenols and their components in experimental allergic asthma. Adv. Exp. Med. Biol. 2013;756:91-98.

    Not in our library10.1007/978-94-007-4549-0_12

  216. 216.

    Ikarashi N., Sato W., Toda T., Ishii M., Ochiai W., Sugiyama K. Inhibitory effect of polyphenol-rich fraction from the bark of Acacia mearnsii on itching associated with allergic dermatitis. Evid. Based Complement. Alternat. Med. 2012.

    Not in our library10.1155/2012/120389

  217. 217.

    Kim M.J., Choung S.Y. Mixture of polyphenols and anthocyanins from Vaccinium uliginosum L. alleviates DNCB-induced atopic dermatitis in NC/Nga Mice. Evid. Based Complement Alternat. Med. 2012.

    Not in our library10.1155/2012/461989

  218. 218.

    Riccio P., Rossano R., Liuzzi G.M. May diet and dietary supplements improve the wellness of multiple sclerosis patients? A molecular approach. Autoimmune Dis. 2010;2010:249842.

    Not in our library10.4061/2010/249842

  219. 219.

    Riccio P. The molecular basis of nutritional intervention inmultiplesclerosis: A narrative review. Complement.Ther. Med. 2011;19:228-237.

    Not in our library10.1016/j.ctim.2011.06.006

  220. 220.

    Xie L., Li X.K., Takahara S. Curcumin has bright prospects for the treatment of multiplesclerosis. Int. Immunopharmacol. 2011;11:323-330.

    Not in our library10.1016/j.intimp.2010.08.013

  221. 221.

    Yoshida S. Preventive or therapeutic agent for pollen allergy, allergic rhinitis, atopic dermatitis, asthma or urticaria, or health food for prevention or improvement or reduction of symptoms thereof. 2004.

    Not in our library

  222. 222.

    Palpu P., Rao C.V., Rawat A.K.S., Ojha S.K., Reddy G.D. Anti-allergic herbal formulation. 2008.

    Not in our library

  223. 223.

    Menon G.R., Fast D.J., Krempin D.W., Goolsby J.N. Anti-Allergy composition and related method. 2008.

    Not in our library

  224. 224.

    Frimman Berg K. Method of treating symptoms of common cold, allergic rhinitis and infections relating to the respiratory tract. 2011.

    Not in our library

  225. 225.

    Olszanecki R., Gebska A., Kozlovski V.I., Gryglewski R.J. Flavonoids and nitric oxide synthase. J. Physiol. Pharmacol. 2002;53:571-584.

    Not in our library

  226. 226.

    Matsuda H., Tokuoka K., Wu J., Shiomoto H., Kubo M. Inhibitory effects of dehydrocorydaline isolated from Corydalis Tuber against type I-IV allergic models. Biol. Pharm. Bull. 1997;20:431-434.

    Not in our library10.1248/bpb.20.431

  227. 227.

    Havsteen B.H. The biochemistry and medical significance of the flavonoids. Pharmacol. Ther. 2002;96:67-202.

    Not in our library10.1016/s0163-7258(02)00298-x

  228. 228.

    Carboni G.P., Contri P., Davalli R. Allergic contact dermatitis from apomorphine. Contact Derm. 1997;36:177-178.

    Not in our library10.1111/j.1600-0536.1997.tb00417.x

  229. 229.

    Waclawski E.R., Aldridge R. Occupational dermatitis from thebaine and codeine. Contact Derm. 1995;33:51.

    Not in our library10.1111/j.1600-0536.1995.tb00449.x

  230. 230.

    Tanaka S., Otsuki T., Matsumoto Y., Hayakawa R., Sugiura M. Allergic contact dermatitis from enoxolone. Contact Derm. 2001;44:192.

    Not in our library10.1034/j.1600-0536.2001.440308-13.x

  231. 231.

    Basketter D.A., Wright Z.M., Colson N.R., Patlewicz G.Y., Pease C.K. Investigation of the skin sensitizing activity of linalool. Contact Derm. 2002;47:161-164.

    Not in our library10.1034/j.1600-0536.2002.470307.x

  232. 232.

    Ríos J.L., Bas E., Recio M.C. Effects of natural products on contact dermatitis. Curr. Med. Chem. Anti Inflamm. Anti Allergy Agents. 2005;4:65-80.

    Not in our library10.2174/1568014053005273

  233. 233.

    Olthof M.R., Hollman P.C., Zock P.L., Katan M.B. Consumption of high doses of chlorogenic acid, present in coffee, or of black tea increases plasma total homocysteine concentrations in humans. Am. J. Clin. Nutr. 2001;73:532-538.

    Not in our library10.1093/ajcn/73.3.532

  234. 234.

    Muller T., Woitalla D., Hauptmann B., Fowler B., Kuhn W. Decrease of methionine and S-adenosylmethionine and increase of homocysteine in treated patients with Parkinson’s disease. Neurosci. Lett. 2001;308:54-56.

    Not in our library10.1016/s0304-3940(01)01972-3

  235. 235.

    Hegarty V.M., May H.M., Khaw K.T. Tea drinking and bone mineral density in older women. Am. J. Clin. Nutr. 2000;71:1003-1425.

    Not in our library10.1093/ajcn/71.4.1003

  236. 236.

    Estruch R., Sacanella E., Mota F., Chiva-Blanch G., Antúnez E., Casals E., Deulofeu R., Rotilio D., Andres-Lacueva C., Lamuela-Raventos R.M., et al. Moderate consumption of red wine, but not gin, decreases erythrocyte superoxide dismutase activity: A randomised crossover trial. Nutr. Metab. Cardiovasc. Dis. 2011;21:46-53.

    Not in our library10.1016/j.numecd.2009.07.006

  237. 237.

    Ward N.C., Hodgson J.M., Croft K.D., Burke V., Beilin L.J., Puddey I.B. The combination of vitamin C and grape-seed polyphenols increases blood pressure: A randomized, double-blind, placebo-controlled trial. J. Hypertens. 2005;23:427-434.

    Not in our library10.1097/00004872-200502000-00026

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