title: Tannic acid modulates NFκB signaling pathway and skin inflammation in NC/Nga mice through PPARγ expression.
abstract: Polyphenolic compound tannic acid, which is mainly found in grapes and green tea, is a potent antioxidant with anticarcinogenic activities. In this present study, we hypothesized that tannic acid could inhibit nuclear factor (NF)κB signaling and inflammation in atopic dermatitis (AD) NC/Nga mice. We have analyzed the effects of tannic acid on dermatitis severity, histopathology and expression of inflammatory signaling proteins in house dust mite extract induced AD mouse skin. In addition, serum levels of T helper (Th) cytokines (interferon (IFN)γ, interleukin (IL)-4) were measured by enzyme-linked immunosorbent assay. Treatment with tannic acid ameliorated the development of AD-like clinical symptoms and effectively inhibited hyperkeratosis, parakeratosis, acanthosis, mast cells and infiltration of inflammatory cells in the AD mouse skin. Serum levels of IFNγ and IL-4 were significantly down-regulated by tannic acid. Furthermore, tannic acid treatment inhibited DfE induced tumor necrosis factor (TNF)α, high mobility group protein (HMG)B1, receptor for advanced glycation end products (RAGE), extracellular signal-regulated kinase (ERK)1/2, NFκB, cyclooxygenase (COX)2, IL-1β and increased the protein expression of peroxisome proliferator-activated receptor (PPAR)γ. Taken together, our results demonstrate that, DfE induced skin inflammation might be mediated through NFκB signaling and tannic acid may be a potential therapeutic agent for AD, which may possibly act via induction of PPARγ protein.
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan.
authors.forename: Vengadeshprabhu
authors.initials: V
authors.lastname: Karuppagounder
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan.
authors.forename: Somasundaram
authors.initials: S
authors.lastname: Arumugam
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan; Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX 77030, USA.
authors.forename: Rajarajan Amirthalingam
authors.initials: RA
authors.lastname: Thandavarayan
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan.
authors.forename: Vigneshwaran
authors.initials: V
authors.lastname: Pitchaimani
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan.
authors.forename: Remya
authors.initials: R
authors.lastname: Sreedhar
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan.
authors.forename: Rejina
authors.initials: R
authors.lastname: Afrin
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan.
authors.forename: Meilei
authors.initials: M
authors.lastname: Harima
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Nomoto
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan.
authors.forename: Shizuka
authors.initials: S
authors.lastname: Miyashita
authors.affiliation: Department of Gastroenterology, Niigata University Graduate School of Medical and Dental Sciences, Niigata City 951-8510, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Department of Cardiology, Yamanashi Prefectural Center Hospital, 1-1-1 Fujimi Kofu, Yamanashi 400-8506, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: Department of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Ueno
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan. Electronic address: watanabe@nupals.ac.jp.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology; D016207:Cytokines / Q000097:blood; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000276:immunology; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D024243:HMGB1 Protein / Q000235:genetics; D007371:Interferon-gamma / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D008407:Mast Cells / Q000187:drug effects; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D012867:Skin / Q000276:immunology / Q000473:pathology; D013634:Tannins / Q000008:administration & dosage / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D039741:Antigens, Dermatophagoides; D016207:Cytokines; D024243:HMGB1 Protein; D016328:NF-kappa B; D047495:PPAR gamma; D013634:Tannins; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D007371:Interferon-gamma; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Cytokine; Nuclear factor kappa B; Peroxisome proliferator-activated receptor; Tannic acid; Tumor necrosis factor