Cardamonin, inhibits pro-inflammatory mediators in activated RAW 264.7 cells and whole blood

Abstract

Some chalcones, such as hydroxychalcones have been reported previously to inhibit major pro-inflammatory mediators such as nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α) and reactive oxygen species production by suppressing inducible enzyme expression via inhibition of the mitogen-activated protein kinase (MAPK) pathway and nuclear translocation of critical transcription factors. In this report, the effects of cardamonin (2′,4′-dihydroxy-6′-methoxychalcone), a chalcone that we have previously isolated from Alpinia rafflesiana, was evaluated upon two cellular systems that are repeatedly used in the analysis of anti-inflammatory bioactive compounds namely RAW 264.7 cells and whole blood. Cardamonin inhibited NO and PGE2 production from lipopolysaccharide-and interferon-γ-induced RAW cells and whole blood with IC50 values of 11.4 μM and 26.8 μM, respectively. Analysis of thromboxane B2 (TxB2) secretion from whole blood either stimulated via the COX-1 or COX-2 pathway revealed that cardamonin inhibits the generation of TxB2 via both pathways with IC50 values of 2.9 and 1.1 μM, respectively. Analysis of IC50 ratios determined that cardamonin was more COX-2 selective in its inhibition of TxB2 with a ratio of 0.39. Cardamonin also inhibited the generation of intracellular reactive oxygen species and secretion of TNF-α from RAW 264.7 cells in a dose responsive manner with IC50 values of 12.8 μM and 4.6 μM, respectively. However, cardamonin was a moderate inhibitor of lipoxygenase activity when tested in an enzymatic assay system, in which not a single concentration tested was able to cause an inhibition of more than 50%. Our results suggest that cardamonin acts upon major pro-inflammatory mediators in a similar fashion as described by previous work on other closely related synthetic hydroxychalcones and strengthens the conclusion of the importance of the methoxyl moiety substitution on the 4′ or 6′ locations of the A benzene ring.

Asperlin From the Marine-Derived Fungus Aspergillus sp. SF-5044 Exerts Anti-inflammatory Effects Through Heme Oxygenase-1 Expression in Murine Macrophages

“…3: A and C). L-NAME, a standard NOS inhibitor (28,29), caused a significant inhibition of iNOS expression ( Figs. 2A and 3A) and NO production (Figs.…”

“…Enzyme-linked immunosorbent assay (ELISA) kits for PGE 2 , TNF-α, and IL1-β were purchased from R&D Systems (Minneapolis, MN, USA). All other chemicals including the HO-1 inducer cobalt protoporphyrin (CoPP) (24,27) and L-NAME (L-N G -nitro arginine methyl ester), a standard NOS inhibitor (28,29), were obtained from Sigma Chemical Co. (St. Louis, MO, USA), unless indicated otherwise. All of the asperlin used in this paper was the same preparation and isolated from Aspergillus sp.…”

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...…”

“…47 It also appears to end up inhibiting prostaglandin E2, tumor necrosis factor a (TNF-a) release, thromboxane B2 production, and intracellular reactive oxygen species generation, all in a dose-dependent manner. 48,54 In most of these studies, RAW264.7 cells were used and analyzed by enzyme-linked immunosorbent assays, western blotting, and interestingly, luciferase gene reporter assays. 84 Wei et al 37 studied the protective effect of cardamonin from acute lung injury in sepsis.…”

4'-Acetamidochalcone Derivatives as Potential Antinociceptive Agents

“…A number of chalcones and their derivatives have also been found to inhibit the synthesis of nitric oxide (NO) and prostaglandins (PG), which are products of the nitric oxide synthase (NOS) and cyclooxygenase (COX) pathways, respectively [2,3]. Recently, Nowakovska published a review of the anti-infective and antiinflammatory activity of chalcones, which constitute a unique template that is associated with diverse biological activities [4].…”