Background: 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.

Background Paraquat (PQ) has been reported to have a high mortality rate. The major target organ of PQ poisoning is the lungs. The pathogenesis of PQ-induced lung injury involves oxidative stress and inflammation. Unfortunately, there is still no effective antidote for PQ poisoning. We hypothesized that aqueous Thunbergia laurifolia (TL) leaf extract is a possible antidote for PQ-induced lung injury. Methods The total phenolic content and caffeic acid content of an aqueous extract of TL leaves were analyzed. Male Wistar rats were randomly divided into four groups (n = 4 per group): the control group (administered normal saline), the PQ group (administered 18 mg/kg body weight (BW) PQ dichloride subcutaneously), the PQ + TL-low-dose (LD) group (administered PQ dichloride subcutaneously and 100 mg/kg BW aqueous TL leaf extract by oral gavage) and the PQ + TL-high-dose (HD) group (administered PQ dichloride subcutaneously and 200 mg/kg BW aqueous TL leaf extract by oral gavage). Malondialdehyde (MDA) levels and lung histopathology were analyzed. In addition, the mRNA expression of NADPH oxidase (NOX), interleukin 1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α) was assessed using reverse transcription-polymerase chain reaction (RT-PCR), and the protein expression of IL-1β and TNF-α was analyzed using immunohistochemistry. Results The total phenolic content of the extract was 20.1 ± 0.39 μg gallic acid equivalents (Eq)/mg extract, and the caffeic acid content was 0.31 ± 0.01 μg/mg. The PQ group showed significantly higher MDA levels and NOX, IL-1β and TNF-α mRNA expression than the control group. Significant pathological changes, including alveolar edema, diffuse alveolar collapse, hemorrhage, leukocyte infiltration, alveolar septal thickening and vascular congestion, were observed in the PQ group compared with the control group. However, the aqueous TL leaf extract significantly attenuated the PQ-induced increases in MDA levels and NOX, IL-1β and TNF-α expressions. Moreover, the aqueous TL leaf extract ameliorated PQ-induced lung pathology. Conclusion This study indicates that aqueous TL leaf extract can ameliorate PQ-induced lung pathology by modulating oxidative stress through inhibition of NOX and by regulating inflammation through inhibition of IL-1β and TNF-α expressions. We suggest that aqueous TL leaf extract can be used as an antidote for PQ-induced lung injury.

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