Inhibition of Lipopolysaccharide-Induced Expression of Inducible Nitric Oxide and Cyclooxygenase-2 by Chiisanoside via Suppression of Nuclear Factor-.KAPPA.B Activation in RAW 264.7 Macrophage Cells

Abstract

The plants belonging to Acanthopanax species (Araliaceae) are traditionally used in Korea as anti-rheumatoid arthritis, anti-inflammatory and anti-diabetic drugs and are recognized to have ginseng-like activities.1,2) 3,4-Secolupanetype triterpenoid family members, such as chiisanoside, chiisanogenin, 22-hydroxychiisanogenin, 24-hydroxychiisanogenin, etc. have been previously isolated from Acanthopanax species.1,3) Chiisanoside, the main terpenoid component of this plant, has been reported to have anti-hepatotoxic, anti-diabetic and antiviral effects, the latter of which was found to be associated with the inhibition of mitogen-induced lymphocyte proliferation. [4][5][6] We previously described the anti-inflammatory effects of chiisanoside and chiisanogenin in the rats induced by carrageenan-and Freund's complete adjuvant. 7) In addition, we demonstrated that chiisanoside can be converted to its aglycon, chiisanogenin by human intestinal bacteria and that chiisanogenin showed more potent cytotoxicity and anti-rotaviral activities. 1)During the inflammatory processes, large amounts of proinflammatory mediators, nitric oxide (NO) and prostaglandin E 2 (PGE 2 ) are generated by the inducible isoforms of NO synthase (iNOS) and cyclooxygenase-2 (COX-2), respectively. 8) In mammalian cells, NO is synthesized by three different isoforms of nitric oxide synthase (NOS), namely, neuronal NOS (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS). Although nNOS and eNOS are constitutively expressed, iNOS is expressed in response to interferon-g, lipopolysccharide (LPS) and to a variety of proinflammatory cytokines.9,10) Cyclooxygenase (COX) is the enzyme that converts arachidonic acid to PGs. Like NOS, COX existed in two isoforms, i.e., COX-1 and COX-2.11) COX-1 is expressed constitutively in most tissues and appears to be responsible for maintaining normal physiological functions. In contrast, COX-2 is detectable in only certain types of tissues and is induced transiently by growth factors, proinflammatory cytokines, tumor promoters and bacterial toxins.12,13) Moreover, elevated levels of COX have been detected in different tumor types and this may account for the excessive production of inflammatory PGs. 14)Nuclear transcription factor kappa-B (NF-kB) is one of the most ubiquitous transcription factors and regulates gene involved in cellular proliferation, inflammatory responses and cell adhesion. The activation of NF-kB has been reported to induce the transcriptions of many pro-inflammatory mediators, e.g., iNOS, COX-2, TNF-a and interleukin (IL)-1b, -6 and -8. 15,16) Our previous investigations of chiisanoside and chiisanogenin demonstrated their anti-inflammatory syndromes in the rat induced by carrageenan and Freund's complete adjuvant reagents. 7) Thus, as a prelude to reveal the underlying mechanisms for the anti-inflammatory effects of chiisanoside and chiisanogenin, we evaluated and compared the effects of various triterpenoid derivatives (Fig. 1) In the present study, the effects of several triterpenes isolate...

Moxifloxacin enhances antiproliferative and apoptotic effects of etoposide but inhibits its proinflammatory effects in THP-1 and Jurkat cells

“…Nuclear factor-kB is a well-known mediator of inflammatory cytokines (Won et al, 2005), and it was shown to be activated during apoptosis following cell incubation with a variety of agents including VP-16 (Usami et al, 1998). Based on our previous and current observations, it seems plausible that MXF decreases VP-16-induced proinflammatory cytokine secretion in THP-1 cells via inhibition of NF-kB activation.…”

Inhibition of inducible nitric oxide synthase by Acanthopanax senticosus extract in RAW264.7 macrophages

“…albeofructus inhibited the NO production and the iNOS expression through the down-regulation of NF-B binding activity in RAW264.7 macrophage cells. It has also been reported that syringaresinol, an active component of Acanthopanax senticosus, suppressed various inflammatory gene expression through inhibiting NF-B activity in SW982 human synovial sarcoma cell line (Won et al, 2005). Considered together, it seems like that Acanthopanax senticosus has anti-inflammatory activity via inhibition of NF-B activation.…”

Lipopolysaccharide induces calcitonin gene‐related peptide in the RAW264.7 macrophage cell line

“…Lipopolysaccharide has been reported to up‐regulate the expression of inflammatory mediators such as IL‐1β, tumour necrosis factor‐α (TNFα), IL‐6, nerve growth factor (NGF), inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2)/prostaglandin E 2 (PGE 2 ) in RAW264.7 macrophages 11–13 . The nuclear factor‐κB (NF‐κB) signalling pathway is involved in LPS‐induced production of inflammatory mediators in this cell line 12,14 .…”