Rosmarinic acid, a major polyphenolic component of Perilla frutescens, reduces lipopolysaccharide (LPS)-induced liver injury in D-galactosamine (D-GalN)-sensitized mice

Naomi Osakabe, Akiko Yasuda, Midori Natsume, Chiaki Sanbongi, Yoji Kato, Toshihiko Osawa, Toshikazu Yoshikawa

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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-α 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-α (TNF-α) mRNA expression in liver and in plasma TNF-α 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 Nε-(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-α production.

Original languageEnglish
Pages (from-to)798-806
Number of pages9
JournalFree Radical Biology and Medicine
Issue number6
Publication statusPublished - 2002 Sep 15



  • Free radicals
  • Liver injury
  • N-(hexanonyl)lysine
  • Nitrotyrosine
  • Perilla
  • Rosmarinic acid

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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