Rosmarinic acid, a major polyphenolic component of Perilla frutescens, reduces lipopolysaccharide (LPS)-induced liver injury in D-galactosamine (D-GalN)-sensitized mice.
The protective activity of rosmarinic acid from Perilla frutescens on liver injury induced by LPS in D-GalN-sensitized mice was examined. We also investigated the effects of antitumor necrosis factor-alpha antibody (anti-TNF), superoxide dismutase (SOD), and aminoguanidine (AG) on this model in order to elucidate the mechanism of rosmarinic acid protection. Perilla extract (PE) and rosmarinic acid (RA) treatments significantly reduced the elevation of plasma asparatate aminotransferase levels, as well as anti-TNF and SOD treatment, compared with controls, but this reduction was not seen in the AG group. These results were confirmed by histological examination using hematoxylin-eosin and in situ terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining. Increases in tumor necrosis factor-alpha (TNF-alpha) mRNA expression in liver and in plasma TNF-alpha levels, which were observed in control mice, were not significantly reduced by PE or RA. PE and RA treatments also did not significantly diminish iNOS mRNA expression or plasma nitrate/nitrite levels. Nitrotyrosine and N(epsilon)-(hexanonyl)lysine (HEL) production, the residue of oxidative stress, was observed in livers from controls, but not in those mice pretreated with PE or RA. These results suggest that the liver protection of RA is due to the scavenging or reducing activities-superoxide or peroxynitirite rather than to inhibition of TNF-alpha production.
Functional Foods Research and Development Laboratory, Meiji Seika Kaisha Ltd., Chiyoda Sakado, Japan. naomi_osakabe@meiji.co.jp
Naomi
N
Osakabe
Akiko
A
Yasuda
Midori
M
Natsume
Chiaki
C
Sanbongi
Yoji
Y
Kato
Toshihiko
T
Osawa
Toshikazu
T
Yoshikawa
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D002934:Cinnamates / Q000494:pharmacology*; D053630:Depsides; D005688:Galactosamine / Q000494:pharmacology*; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000293:injuries / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008956:Models, Chemical; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D018384:Oxidative Stress; D031344:Perilla frutescens / Q000378:metabolism*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000097123:Rosmarinic Acid
D000410:Alanine Transaminase; D002934:Cinnamates; D053630:Depsides; D005688:Galactosamine; D008070:Lipopolysaccharides; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D010975:Platelet Aggregation Inhibitors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000097123:Rosmarinic Acid; C496317:Nos2 protein, mouse