title: Rosmarinic acid inhibits lung injury induced by diesel exhaust particles.
abstract: Epidemiological and experimental studies have suggested that diesel exhaust particles (DEP) may be involved in recent increases in lung diseases. DEP has been shown to generate reactive oxygen species. Intratracheal instillation of DEP induces lung inflammation and edema in mice. Rosmarinic acid is a naturally occurring polyphenol with antioxidative and anti-inflammatory activities. We investigated the effects of rosmarinic acid on lung injury induced by intratracheal administration of DEP (500 microg/body) in mice. Oral supplementation with administration of rosmarinic acid (2 mg/body for 3 d) inhibited DEP-induced lung injury, which was characterized by neutrophil sequestration and interstitial edema. DEP enhanced the lung expression of keratinocyte chemoattractant (KC), interleukin-1beta, monocyte chemoattractant protein-1, and macrophage inflammatory protein-1alpha, which was inhibited by treatment with rosmarinic acid. DEP enhanced expression of iNOS mRNA and formation of nitrotyrosine and 8-OHdG in the lung, which was also inhibited by rosmarinic acid. These results suggest that rosmarinic acid inhibits DEP-induced lung injury by the reduction of proinflammatory molecule expression. Antioxidative activities of rosmarinic acid may also contribute to its protective effects.
authors.affiliation: Health and Bioscience Laboratories, Meiji Seika Kaisha, Ltd, Saitama, Japan. chiaki_sambongi@meiji.co.jp
authors.forename: Chiaki
authors.initials: C
authors.lastname: Sanbongi
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Takano
authors.forename: Naomi
authors.initials: N
authors.lastname: Osakabe
authors.forename: Naoko
authors.initials: N
authors.lastname: Sasa
authors.forename: Midori
authors.initials: M
authors.lastname: Natsume
authors.forename: Rie
authors.initials: R
authors.lastname: Yanagisawa
authors.forename: Ken-ichiro
authors.initials: K
authors.lastname: Inoue
authors.forename: Yoji
authors.initials: Y
authors.lastname: Kato
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Osawa
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D018893:Bronchoalveolar Lavage; D018932:Chemokine CCL2 / Q000096:biosynthesis; D054407:Chemokine CCL4; D018925:Chemokines / Q000096:biosynthesis; D002934:Cinnamates / Q000378:metabolism / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D053630:Depsides; D005419:Flavonoids / Q000737:chemistry; D005609:Free Radicals; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D055370:Lung Injury; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008956:Models, Chemical; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D018384:Oxidative Stress; D010636:Phenols / Q000737:chemistry; D059808:Polyphenols; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism; D001335:Vehicle Emissions / Q000009:adverse effects*; D000097123:Rosmarinic Acid
chemical_list: D000975:Antioxidants; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D018925:Chemokines; D002934:Cinnamates; D016207:Cytokines; D053630:Depsides; D005419:Flavonoids; D005609:Free Radicals; D019402:Macrophage Inflammatory Proteins; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D010636:Phenols; D059808:Polyphenols; D012333:RNA, Messenger; D014443:Tyrosine; D001335:Vehicle Emissions; D000097123:Rosmarinic Acid; C002744:3-nitrotyrosine; C496317:Nos2 protein, mouse