Phenolic substances from Phagnalon rupestre protect against 2,4,6-trinitrochlorobenzene-induced contact hypersensitivity.

2-isoprenylhydroquinone-1-glucoside (1), 3,5-dicaffeoylquinic acid (2), and 3,5-dicaffeoylquinic acid methyl ester (3), isolated from Phagnalon rupestre, improved the contact hypersensitivity response to 2,4,6-trinitrochlorobenzene in mice. These phenolics reduced ear swelling and IL-1β content by 50% 24 h after challenge; in addition, 2 inhibited tumor necrosis factor-α by 53%. All three compounds also reduced interleukin-2 content by 50% 72 h after challenge. Both 2 and 3 inhibited metalloproteinase-9 levels in the skin lesions by 66% and 41%, respectively, and lowered cyclooxygenase-2 expression by 44% and 49%, respectively, at 24 h. Moreover, 2 was effective against atopic dermatitis induced by repeated application of 2,4,6-trinitrochlorobenzene; it attenuated edema by over 40% from day 7 and inhibited inflammatory cell infiltration by 44% at day 22. In addition, 1-3 reduced metalloproteinase-9 expression in a dose-dependent manner in macrophages RAW 264.7 stimulated with lipopolysaccharide. Thus, compounds 2 and 3 were found to exhibit a greater activity against contact hypersensitivity than 1.

[1]  M. Recio,et al.  Interaction of dicaffeoylquinic derivatives with peroxynitrite and other reactive nitrogen species. , 2008, Archives of biochemistry and biophysics.

[2]  C. Takada,et al.  Analyses of a mouse model of the dermatitis caused by 2,4,6-trinitro-1-chlorobenzene (TNCB)-repeated application. , 2005, Journal of dermatological science.

[3]  Sukta Das,et al.  Inhibition of growth, induction of apoptosis and alteration of gene expression by tea polyphenols in the highly metastatic human lung cancer cell line NCI-H460. , 2005, Asian Pacific journal of cancer prevention : APJCP.

[4]  M. Recio,et al.  Effects of plant alkylphenols on cytokine production, tyrosine nitration and inflammatory damage in the efferent phase of contact hypersensitivity , 2007, British journal of pharmacology.

[5]  M. Recio,et al.  Inhibition of xanthine oxidase by phenolic conjugates of methylated quinic acid. , 2003, Planta medica.

[6]  T. Shiohara,et al.  Animal models for atopic dermatitis: are they relevant to human disease? , 2004, Journal of dermatological science.

[7]  F. Staedtler,et al.  Gene expression profiling of skin and draining lymph nodes of rats affected with cutaneous contact hypersensitivity , 2006, Inflammation Research.

[8]  Chi-Tang Ho,et al.  Differential effects of theaflavin monogallates on cell growth, apoptosis, and Cox-2 gene expression in cancerous versus normal cells. , 2000, Cancer research.

[9]  D. Harada,et al.  Effect of orally administered rolipram, a phosphodiesterase 4 inhibitor, on a mouse model of the dermatitis caused by 2,4,6-trinitro-1-chlorobenzene (TNCB)-repeated application. , 2006, European journal of pharmacology.

[10]  M. Recio,et al.  Phagnalon rupestre as a Source of Compounds Active on Contact Hypersensitivity , 2002, Planta medica.

[11]  M. Recio,et al.  Isoprenylhydroquinone glucoside: a new non-antioxidant inhibitor of peroxynitrite-mediated tyrosine nitration. , 2005, Nitric oxide : biology and chemistry.

[12]  M. Recio,et al.  Protein Tyrosine Nitration Induced by Heme/Hydrogen Peroxide: Inhibitory Effect of Hydroxycinnamoyl Conjugates , 2006, Planta medica.

[13]  C. Griffiths,et al.  Cytokines and Langerhans cell mobilisation in mouse and man. , 2005, Cytokine.

[14]  Jae-Hong Kim,et al.  Lipopolysaccharide Induces Matrix Metalloproteinase-9 Expression via a Mitochondrial Reactive Oxygen Species-p38 Kinase-Activator Protein-1 Pathway in Raw 264.7 Cells1 , 2004, The Journal of Immunology.

[15]  S. Teuber,et al.  Ellagic acid and polyphenolics present in walnut kernels inhibit in vitro human peripheral blood mononuclear cell proliferation and alter cytokine production , 2010, Annals of the New York Academy of Sciences.

[16]  M. Recio,et al.  Modulation of protein tyrosine nitration and inflammatory mediators by isoprenylhydroquinone glucoside. , 2007, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[17]  G. Tucker,et al.  Effects of dietary polyphenols on gene expression in human vascular endothelial cells , 2008, Proceedings of the Nutrition Society.

[18]  J. Young,et al.  Edema and cell infiltration in the phorbol ester-treated mouse ear are temporally separate and can be differentially modulated by pharmacologic agents , 1989, Agents and Actions.

[19]  C. Rice-Evans,et al.  Flavonoids: antioxidants or signalling molecules? , 2004, Free radical biology & medicine.

[20]  M. Recio,et al.  Effects of caffeoyl conjugates of isoprenyl-hydroquinone glucoside and quinic acid on leukocyte function. , 2002, Life sciences.

[21]  H. Weiner,et al.  Gelatinases (MMP-2 and MMP-9) are preferentially expressed by Th1 vs. Th2 cells , 2005, Journal of Neuroimmunology.