title: Anti-inflammatory Effect of Methyl Gallate on Experimental Arthritis: Inhibition of Neutrophil Recruitment, Production of Inflammatory Mediators, and Activation of Macrophages.
abstract: Methyl gallate (MG) is a prevalent phenolic acid in the plant kingdom, and its presence in herbal medicines might be related to its remarkable biological effects, such as its antioxidant, antitumor, and antimicrobial activities. Although some indirect evidence suggests anti-inflammatory activity for MG, there are no studies demonstrating this effect in animal models. Herein, we demonstrated that MG (0.7-70 mg/kg) inhibited zymosan-induced experimental arthritis in a dose-dependent manner. The oral administration of MG (7 mg/kg) attenuates arthritis induced by zymosan, affecting edema formation, leukocyte migration, and the production of inflammatory mediators (IL-1β, IL-6, TNF-α, CXCL-1, LTB4, and PGE2). Pretreatment with MG inhibited in vitro neutrophil chemotaxis elicited by CXCL-1, as well as the adhesion of these cells to TNF-α-primed endothelial cells. MG also impaired zymosan-stimulated macrophages by inhibiting IL-6 and NO production, COX-2 and iNOS expression, and intracellular calcium mobilization. Thus, MG is likely to present an anti-inflammatory effect by targeting multiple cellular events such as the production of various inflammatory mediators, as well as leukocyte activation and migration.
authors.affiliation: Laboratory of Applied Pharmacology, Farmanguinhos, and ‡National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Oswaldo Cruz Foundation (Fiocruz) , Rio de Janeiro, RJ, Brazil.
authors.forename: Luana Barbosa
authors.initials: LB
authors.lastname: Correa
authors.affiliation: Laboratory of Applied Pharmacology, Farmanguinhos, and ‡National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Oswaldo Cruz Foundation (Fiocruz) , Rio de Janeiro, RJ, Brazil.
authors.forename: Tatiana Almeida
authors.initials: TA
authors.lastname: Pádua
authors.affiliation: Laboratory of Applied Pharmacology, Farmanguinhos, and ‡National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Oswaldo Cruz Foundation (Fiocruz) , Rio de Janeiro, RJ, Brazil.
authors.forename: Leonardo Noboru
authors.initials: LN
authors.lastname: Seito
authors.affiliation: Laboratory of Applied Pharmacology, Farmanguinhos, and ‡National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Oswaldo Cruz Foundation (Fiocruz) , Rio de Janeiro, RJ, Brazil.
authors.forename: Thadeu Estevam Moreira Maramaldo
authors.initials: TE
authors.lastname: Costa
authors.affiliation: Laboratory of Applied Pharmacology, Farmanguinhos, and ‡National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Oswaldo Cruz Foundation (Fiocruz) , Rio de Janeiro, RJ, Brazil.
authors.forename: Magaiver Andrade
authors.initials: MA
authors.lastname: Silva
authors.affiliation: Laboratory of Applied Pharmacology, Farmanguinhos, and ‡National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Oswaldo Cruz Foundation (Fiocruz) , Rio de Janeiro, RJ, Brazil.
authors.forename: André Luis Peixoto
authors.initials: AL
authors.lastname: Candéa
authors.affiliation: Laboratory of Applied Pharmacology, Farmanguinhos, and ‡National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Oswaldo Cruz Foundation (Fiocruz) , Rio de Janeiro, RJ, Brazil.
authors.forename: Elaine Cruz
authors.initials: EC
authors.lastname: Rosas
authors.affiliation: Laboratory of Applied Pharmacology, Farmanguinhos, and ‡National Institute for Science and Technology on Innovation on Neglected Diseases (INCT/IDN), Center for Technological Development in Health (CDTS), Oswaldo Cruz Foundation (Fiocruz) , Rio de Janeiro, RJ, Brazil.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Henriques
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001169:Arthritis, Experimental; D001938:Brazil; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced; D018836:Inflammation Mediators / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects*; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D020556:Neutrophil Infiltration / Q000187:drug effects*; D052247:Nitric Oxide Synthase Type II; D010946:Plants, Medicinal / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015054:Zymosan / Q000494:pharmacology
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C052082:methyl gallate; D005707:Gallic Acid; D015054:Zymosan; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2