The effects of cardamonin on lipopolysaccharide‐induced inflammatory protein production and MAP kinase and NFκB signalling pathways in monocytes/macrophages

Abstract

Background and purpose: In this study we examined the effect of the natural product cardamonin, upon lipopolysaccharide (LPS)-induced inflammatory gene expression in order to attempt to pinpoint the mechanism of action. Experimental approaches: Cardamonin was isolated from the Greek plant A. absinthium L. Its effects were assessed on LPSinduced nitrite release and iNOS and COX-2 protein expression in two macrophage cell lines. Western blotting was used to investigate its effects on phosphorylation of the mitogen activated protein (MAP) kinases, ERK, JNK and p38 MAP kinase, and activation of the NFkB pathway, at the level of IkBa degradation and phosphorylation of NFkB. Also its effects on NFkB and GAS/GAF-DNA binding were assessed by EMSA. Key results: Cardamonin concentration-dependently inhibited both NO release and iNOS expression but had no effect on COX-2 expression. It did not affect phosphorylation of the MAP kinases, degradation of IkBa or phosphorylation of NFkB. However, it inhibited NFkB DNA-binding in both LPS-stimulated cells and nuclear extracts of the cells (in vitro). It also inhibited IFNg-stimulated iNOS induction and GAS/GAF-DNA binding. Conclusions and implications:These results show that the inhibitory effect of cardamonin on LPS-induced iNOS induction is not mediated via effects on the initial activation of the NFkB or MAP kinase pathways but is due to a direct effect on transcription factor binding to DNA. However, although some selectivity in cardamonin's action is implicated by its inability to affect COX-2 expression, its exact mechanism(s) of action has yet to be identified.

The anti-inflammatory effect and potential mechanism of cardamonin in DSS-induced colitis

“…Chalcones are naturally occurring compounds belonging to the flavonoid family and exhibiting a broad spectrum of biological activities, including anti-cancer, anti-inflammatory, anti-oxidative, anti-viral, anti-fungal, and anti-allergic activities (12). Cardamonin (2=,4=-dihydroxy-6=-methoxychalcone) is a chalcone mainly existed in the seeds of Alpinia Katsumadai Hayata, a plant that has been widely used in oriental medicine to treat emesis and gastric disorders (20).…”

Dietary chalcones with chemopreventive and chemotherapeutic potential

“…NF-jB activation and related iNOS production in LPS-stimulated cells were inhibited by a direct effect on the capacity of the transcription factor to bind DNA [50]. Interestingly, Israf et al [60] reported inhibition of COX-2 and iNOS expression by cardamonin (22) via dose-dependent suppression of IjBa phosphorylation and degradation in LPS-induced RAW 264.7 macrophages, clearly describing a cell-type-specific effect of this compound.…”

An Overview on Cardamonin

“…3 Cardamonin's name comes from the fact that it can be found in cardamom spice (Fig. 4), but since the first article where it was described, 22 it has been found in many other (some of them edible) plant species, such as Alpinia blepharocalyx, 23,24 Alpinia gagnepainii, 25 Alpinia conchigera, 26,27 Alpinia hainanensis, [28][29][30][31][32][33][34][35][36][37][38][39][40] Alpinia malaccensis, 41 Alpinia mutica, 42,43 Alpinia pricei, 44 Alpinia rafflesiana, [45][46][47][48] Alpinia speciosa, 22,49,50 Amomum subulatum, 51 Artemisia absinthium, 52 Boesenbergia pandurata, [53][54][55][56][57][58][59][60] Boesenbergia rotunda, 61,62 Carya cathayensis, 63 Cedrelopsis grevei, 64 Combretum apiculatum, 65 Comptonia pere...…”

“…Anti-inflammatory, antineoplastic, and antioxidant activity Several authors 26,36,46,52,81 have aimed to explain the antiinflammatory activity of cardamonin by fully observing its influence over the signaling pathway of the nuclear factorjB (NF-jB)-a protein complex that controls transcription of DNA and plays a crucial role in regulating immune responses to infection 1,82 -and detail the mechanism of action on the lipopolysaccharide (LPS)-induced inflammatory gene expression. A 27% inhibition of LPS-induced NO production with a 1 lM can be found in literature.…”