Dioscorealide B suppresses LPS‐induced nitric oxide production and inflammatory cytokine expression in RAW 264.7 macrophages: The inhibition of NF‐κB and ERK1/2 activation

Abstract

Dioscorealide B (DB), a naphthofuranoxepin has been purified from an ethanolic extract of the rhizome of Dioscorea membranacea Pierre ex Prain & Burkill which has been used to treat inflammation and cancer in Thai Traditional Medicine. Previously, DB has been reported to have anti-inflammatory activities through reducing nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) production in lipopolysaccharides (LPS)-induced RAW 264.7 macrophage cells. In this study, the mechanisms of DB on LPS-induced NO production and cytokine expression through the activation of nuclear factor-kappaB (NF-kappaB) and ERK1/2 are demonstrated in RAW 264.7 cells. Through measurement with Griess's reagent, DB reduced NO level with an IC(50) value of 2.85 +/- 0.62 microM that was due to the significant suppression of LPS-induced iNOS mRNA expression as well as IL-1beta, IL-6, and IL-10 mRNA at a concentration of 6 microM. At the signal transduction level, DB significantly inhibited NF-kappaB binding activity, as determined using pNFkappaB-Luciferase reporter system, which action resulted from the prevention of IkappaBalpha degradation. In addition, DB in the range of 1.5-6 microM significantly suppressed the activation of the ERK1/2 protein. In conclusion, the molecular mechanisms of DB on the inhibition of NO production and mRNA expression of iNOS, IL-1beta, IL-6, and IL-10 were due to the inhibition of the upstream kinases activation, which further alleviated the NF-kappaB and MAPK/ERK signaling pathway in LPS-induced RAW264.7 macrophage cells.

<i>Anethum graveloens</i> Flower Extracts Inhibited a Lipopolysaccharide-Induced Inflammatory Response by Blocking iNOS Expression and NF-κB Activity in Macrophages

“…When it is bound by lipopolysaccharide-binding protein (LBP), the complex is recognized by the TLR4-CD14 complex. [7][8][9] In accordance with this process, an activated macrophage begins intracellular signal transduction. LPS-mediated signaling in macrophages can be classified into two pathways.…”

Dioscorea Extract (DA-9801) Modulates Markers of Peripheral Neuropathy in Type 2 Diabetic db/db Mice

“…The tuber storage protein of Dioscorea alata, dioscorin (Hsu et al, 2002), and red mold Dioscorea (Wu et al, 2009) exhibit angiotensin-converting enzyme inhibitory activities. Moreover, some Dioscorea species and their constituents are known to have anti-inflammatory properties (Oh and Lim, 2008;Hiransai et al, 2010;Nguelefack et al, 2010;Mbiantcha et al, 2011). Considering the previous references, the inhibitory activities of DA-9801 on diabetic neuropathy may be exerted by multi-targeted pharmacological activities of the Dioscorea species.…”

Housefly Maggots (Musca domestica) Protein-enriched Fraction/ extracts (PE) Inhibit Lipopolysaccharide-induced Atherosclerosis Pro-inflammatory Responses

“…The positive control group was also treated with simvastatin (15 g/mL), and then 200 L culture supernatant was collected and assayed for the presence of cytokines, including TNF , IL-1 and MCP-1 12) .…”