demethoxycurcumin and Inflammation

Pulmonary problems are among the most frequent chronic complications of sulfur mustard (SM) intoxication and are often accompanied by deregulated production of pro-inflammatory cytokines. Curcuminoids, comprising curcumin, demethoxycurcumin and bisdemethoxycurcumin, are phytochemicals with remarkable anti-inflammatory properties that are derived from dried rhizomes of the plant Curcuma longa L. (turmeric). The present pilot study aimed to investigate the clinical effects of supplementation with curcuminoids on markers of pulmonary function and systemic inflammation in SM-intoxicated subjects. In a randomized double-blind placebo-controlled trial, 89 male subjects who were suffering from chronic SM-induced pulmonary complications were recruited and assigned to either curcuminoids (500 mg TID per oral; n=45) or placebo (n=44) for a period of 4 weeks. Efficacy measures were changes in the spirometric parameters (FVC, FEV1, FEV1/FVC) and serum levels of inflammatory mediators including interleukins 6 (IL-6) and 8 (IL-8), tumor necrosis factor-α (TNFα), transforming growth factor-β (TGFβ), high-sensitivity C-reactive protein (hs-CRP), calcitonin gene related peptide (CGRP), substance P and monocyte chemotactic protein-1 (MCP-1). 78 subjects completed the trial. Although FEV1 and FVC remained comparable between the groups, there was a greater effect of curcuminoids vs. placebo in improving FEV1/FVC (p=0.002). Curcuminoids were also significantly more efficacious compared to placebo in modulating all assessed inflammatory mediators: IL-6 (p<0.001), IL-8 (p=0.035), TNFα (p<0.001), TGFβ (p<0.001), substance P (p=0.016), hs-CRP (p<0.001), CGRP (p<0.001) and MCP-1 (p<0.001). Curcuminoids were safe and well-tolerated throughout the trial. Short-term adjunctive therapy with curcuminoids can suppress systemic inflammation in patients suffering from SM-induced chronic pulmonary complications.

Topics: Adult; Anti-Inflammatory Agents; Chemical Warfare Agents; Chronic Disease; Curcumin; Cytokines; Diarylheptanoids; Double-Blind Method; Forced Expiratory Volume; Humans; Inflammation; Inflammation Mediators; Lung Diseases; Male; Middle Aged; Mustard Gas; Pilot Projects; Treatment Outcome; Vital Capacity

The inflammatory radicular pain induced by lumbar disc herniation (LDH) is a serious problem worldwide. Demethoxycurcumin (DMC) is a yellow pigment derived from turmeric. Although it is considered a safe natural compound for managing inflammation-associated diseases, but the molecular mechanisms of LDH remain to be elucidated. In the current study, DMC reduced the production of IL-1β, IL-4, and IL-6 in nucleus pulposus (NP) cells subjected to TNF-α-induced inflammation. Moreover, the inhibitory mechanism was activated upon suppression of activation of MAPKs and NF-κB signalling in NP cells. Further experiments with LDH model rats supported the in vitro results. These studies expand our knowledge of the effect of DMC on LDH; DMC may be a viable alternative to the drugs used to treat LDH.

Topics: Animals; Diarylheptanoids; Inflammation; Intervertebral Disc Degeneration; Intervertebral Disc Displacement; NF-kappa B; Rats

It is known that inducible nitric oxide synthase (iNOS)/nitric oxide (NO) plays an integral role during intestinal inflammation, an important factor for colon cancer development. Natural compounds from Curcuma longa L. (Zingiberaceae) have long been a potential source of bioactive materials with various beneficial biological functions. Among them, a major active curcuminoid, demethoxycurcumin (DMC) has been shown to possess anti-inflammatory properties in lipopolysaccharide (LPS)-activated macrophages or microglia cells. However, the role of DMC on iNOS expression and NO production in an in vitro inflamed human intestinal mucosa model has not yet been elucidated. This study concerned inhibitory effects on iNOS expression and NO production of DMC in inflamed human intestinal Caco-2 cells. An in vitro model was generated and inhibitory effects on NO production of DMC at 65 μM for 24-96 h were assessed by monitoring nitrite levels. Expression of iNOS mRNA and protein was also investigated. DMC significantly decreased NO secretion by 35-41% in our inflamed cell model. Decrease in NO production by DMC was concomitant with down-regulation of iNOS at mRNA and protein levels compared to proinflammatory cytokine cocktail and LPS-treated controls. Mechanism of action of DMC may be partly due to its potent inhibition of the iNOS pathway. Our findings suggest that DMC may have potential as a therapeutic agent against inflammation-related diseases, especially in the gut.

Topics: Anti-Inflammatory Agents; Caco-2 Cells; Cell Line, Tumor; Curcuma; Curcumin; Diarylheptanoids; Humans; Inflammation; Intestinal Mucosa; Lipopolysaccharides; Nitric Oxide; Nitric Oxide Synthase Type II; Plant Preparations; RNA, Messenger

Our previous report has showed that demethoxycurcumin (DMC), a natural derivative of curcumin (Cur), exhibited stronger inhibitory activity on nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) production compared with Cur in lipopolysaccharide (LPS) activated rat primary microglia. In the present study, the effect and possible mechanism of DMC on the production of pro-inflammatory mediators in LPS-activated N9 microglial cells were further investigated. The results showed that DMC significantly suppressed the NO production induced by LPS in N9 microglial cells through inhibiting the protein and mRNA expression of inducible NO synthase (iNOS). DMC also decreased LPS-induced TNF-alpha and IL-1beta expression at both transcriptional and protein level in a concentration-dependent manner. Further studies revealed that DMC blocked IkappaBalpha phosphorylation and degradation, inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs). Moreover, the level of intracellular reactive oxygen species (iROS) was significantly increased by LPS, which is mainly mediated by the up-regulated expression of gp91phox, the catalytic subunit of nicotinamide adenine dinucleotide phosphate reduced (NADPH) oxidase. Both DMC and Cur could markedly decrease iROS production and the expression of NADPH oxidase induced by LPS, with more potent inhibitory activity of DMC. In summary, these data suggest that DMC exerts its in vitro anti-inflammatory effect in LPS-activated N9 microglial cells by blocking nuclear factor-kappaB (NF-kappaB) and MAPKs activation, which may be partly due to its potent down-regulation of the NADPH-derived iROS production.

Topics: Animals; Anti-Inflammatory Agents; Biphenyl Compounds; Blotting, Western; Cell Survival; Curcumin; Diarylheptanoids; Down-Regulation; Inflammation; Interleukin-1beta; Lipopolysaccharides; Macrophage Activation; Mice; Microglia; Mitogen-Activated Protein Kinases; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase Type II; Nitrites; Picrates; Reactive Oxygen Species; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Tumor Necrosis Factor-alpha