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.

AIM OF THE STUDY: 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. CONCLUSION: 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.

Mitogen activated protein kinases are prime signalling enzymes in nitric oxide production induced by soluble ß-glucan from Sparassis crispa.

Sparassis crispa (SC) is an edible mushroom that harbours ß-glucans reported to possess immunostimulatory and anticancer properties. The role of SC in regulating the functional activation of macrophages is yet to be fully elucidated. The objective of this study was to investigate the molecular mechanism underlying the immune-stimulatory function of Sparassis crispa soluble ß-glucan (Sc-SG) on macrophages. According to this study, Sc-SG was able to stimulate nitric oxide (NO) production as well as enhance the expression of inducible NO synthase (iNOS) from macrophage-like RAW264.7 cells. NO production was strongly suppressed by mitogen-activated protein kinase (MAPK) inhibitors such as U0126, extracellular signal-regulated kinase, SB203580, a p38 inhibitor, and SP600125, a c-Jun N-terminal kinase inhibitor. Thus, indicating that Sc-SG-induced NO release is possibly mediated by MAPK. Sc-SG induced phosphorylation of extracellular signal-regulated kinase, p38, and JNK in a time-dependent manner. Moreover, Sc-SG triggered the phosphorylation and translocation of c-Jun and c-Fos, components of the transcription factor AP-1, activated by MAPK. The results of this study suggest that MAPK may be a major signaling enzyme that regulates the Sc-SG-mediated NO production in macrophages.