Rosmarinic acid protects against experimental sepsis by inhibiting proinflammatory factor release and ameliorating hemodynamics.
The present study was to investigate the effects of rosmarinic acid (RA) in cultured RAW264.7 cells and experimental model of sepsis induced by cecal ligation and puncture in rats and the potential mechanism. Results showed that RA concentration dependently down-regulated the levels of TNF-alpha, IL-6, and high-mobility group box 1 protein in LPS-induced RAW264.7 cells, inhibited the IkappaB kinase pathway, and modulated nuclear factor-kappaB. Intravenous injection of RA alone or in combination with imipenem reduced cecal ligation and puncture-induced lethality in rats. In addition, serum levels of TNF-alpha, IL-6, high-mobility group box 1 protein, triggering receptor expressed on myeloid cells, and endotoxin were down-regulated; in contrast, serum level of IL-10 was up-regulated. Amelioration of hemodynamics and decrease in serum enzyme activities and myeloperoxidase in lung, liver, and small intestine were also observed after RA injection. These data indicate that the antisepsis effect of RA was mediated by decreasing local and systemic levels of a wide spectrum of inflammatory mediators. This article provides the first evidence that RA has the capacity to inactivate inflammatory response in sepsis. The anti-inflammatory mechanism of RA may inhibit activation of the nuclear factor- kappaB pathway by inhibiting IkappaB kinase activity.
Jiang
Wang-Lin
WL
College of Marine Life Science, Ocean University of China, Qingdao, People's Republic of China.
Chen
Xi-Guang
XG
Qu
Gui-Wu
GW
Yue
Xi-Dian
XD
Zhu
Hai-Bo
HB
Tian
Jing-Wei
JW
Fu
Feng-Hua
FH
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002934:Cinnamates / Q000494:pharmacology*; D053630:Depsides / Q000494:pharmacology*; D004195:Disease Models, Animal; D004731:Endotoxins / Q000378:metabolism; D005786:Gene Expression Regulation; D006439:Hemodynamics; D006801:Humans; D015378:Imipenem / Q000494:pharmacology; D007249:Inflammation / Q000473:pathology*; D008297:Male; D051379:Mice; D022423:Myeloid Cells / Q000166:cytology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000188:drug therapy* / Q000517:prevention & control; D014212:Tretinoin; D000097123:Rosmarinic Acid
D000900:Anti-Bacterial Agents; D002934:Cinnamates; D053630:Depsides; D004731:Endotoxins; D015378:Imipenem; D014212:Tretinoin; D000097123:Rosmarinic Acid