Inhibitory effect of Sanguisorba officinalis ethanol extract on NO and PGE₂ production is mediated by suppression of NF-κB and AP-1 activation signaling cascade.
OBJECTIVE
Sanguisorba officinalis, a well known valuable medicinal plant in Korea, China and Japan used traditionally for the treatment of inflammatory and metabolic diseases such as diarrhea, chronic intestinal infections, duodenal ulcers, and bleeding. Recent studies have revealed that its aqueous or ethanolic extracts exhibit a variety of pharmacological activities such as anti-oxidative, anti-cancer, anti-lipid peroxidation, anti-atherogenic, and vasorelaxant effects. Systematic studies on the anti-inflammatory effect of this plant and its molecular mechanisms have not yet been fully investigated. Ethanol extract of Sanguisorba officinalis (So-EE) the lipopolysaccharide (LPS)-stimulated macrophages and production of inflammatory mediators were employed to assess these properties.


RESULTS
So-EE significantly suppressed the production of nitric oxide (NO) and prostaglandin (PG) E(2) from LPS-activated RAW264.7 cells and peritoneal macrophages in a dose-dependent manner. This extract effectively diminished the mRNA levels of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2, implying that the blockade is generated at the transcriptional level. So-EE strongly blocked the activation and translocation of NF-κB and AP-1 by suppressing the upstream kinases including inhibitor of κBα (IκBα), IκBα kinase (IKK), Akt (protein kinase B), phosphoinositide-dependent kinase 1 (PDK1), p85/phosphoinositide-3-kinase (PI3K), and mitogen activated protein kinase (MAPK) such as extracellular signal-regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK). Moreover, So-EE suppressed the phosphorylation of Src, its kinase activity, and complex formation between Src and p85.


CONCLUSIONS
This study suggests that So-EE has a potent anti-inflammatory activity mediated by NF-κB, and AP-1 inhibitory properties linked to the suppression of Src and MAPK activation.
Yu
Tao
T
College of Biomedical Science, Institute of Bioscience and Biotechnology, Kangwon National University, Chuncheon 200-701, Republic of Korea.
Lee
Yong Jin
YJ
Yang
Hyun Mo
HM
Han
Soryu
S
Kim
Jae Hun
JH
Lee
Yoonsuk
Y
Kim
Changhyuk
C
Han
Moon Hi
MH
Kim
Mi-Yeon
MY
Lee
Jaehwi
J
Cho
Jae Youl
JY
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D015232:Dinoprostone / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D017930:Genes, Reporter; D047468:Immunoprecipitation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D031993:Sanguisorba / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects*; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D016328:NF-kappa B; D010936:Plant Extracts; D018808:Transcription Factor AP-1; D009569:Nitric Oxide; D015232:Dinoprostone