Resveratrol and Piceatannol Inhibit iNOS Expression and NF-κ B Activation in Dextran Sulfate Sodium-Induced Mouse Colitis

Abstract

Inflammatory tissue injury has been implicated in tumor promotion and progression. 3,5,4'-trihydroxy-trans-stilbene (resveratrol) and 3,4,3', 5'-tetrahydroxy-trans-stilbene (piceatannol), 2 structurally related plant polyphenols, have been reported to possess antioxidant, anti-inflammatory, and chemopreventive properties. This study was aimed at investigating the possible protective effects of resveratrol and piceatannol against dextran sulfate sodium (DSS)-induced inflammation in mouse colonic mucosa. Administration of DSS (2.5%) in drinking water for 7 days to male ICR mice resulted in colitis and elevated expression of inducible nitric oxide synthase (iNOS) and activation of nuclear factor-kappa B (NF-kappaB), a major transcription factor known to upregulate proinflammatory gene expression. Phosphorylation of extracellular signal-regulated kinase (ERK) and signal transducer and activator of transcription-3 (STAT3) was also enhanced after DSS treatment. Oral administration of resveratrol or piceatannol (10 mg/kg body weight each) for 7 constitutive days attenuated the DSS-induced inflammatory injury, upregulation of iNOS expression, and activation of NF-kappaB, STAT3, and ERK.

Vidofludimus Inhibits Colonic Interleukin-17 and Improves Hapten-Induced Colitis in Rats by a Unique Dual Mode of Action

“…Indeed, activation of these pathways has been described in conjunction with dextran sulfate sodium-induced colitis in mice and TNBS-induced colitis in rodents (Bai et al, 2007;Kretzmann et al, 2008;Youn et al, 2009;Fitzpatrick et al, 2011b). Moreover, we have reported that Vido inhibits activation of these intracellular signaling pathways in the mouse colon and murine splenocytes (Fitzpatrick et al, 2011b).…”

Effects of Resveratrol on Inflammatory Bowel Disease: A Review

“…In a majority of studies, weight loss was less in animals given Resveratrol [13,15,16,20,21,23,24,28,33,39]. While few studies showed no difference between groups [37,38].…”

“…Inducible nitric oxide synthase (iNOS), which initiates NO production, is up regulated in a state of chronic intestinal inflammation [27]. Resveratrol generally diminishes iNOS protein expression [13,16,28] and NO production [29,30]. One study dissimilarly found resveratrol to raise NO levels above baseline values [21].…”

“…With resveratrol supplementation, NF-κB p65 subunit activity is inhibited through attenuating attenuate nuclear factor of kappa B inhibitor, alpha (IκBα) phosphorylation, IκB kinase beta (IKKβ) activation, extracellular signal-regulated kinases (ERK) phosphorylation, signal transducer and activator of transcription 3 (STAT3) activation and NF-κB DNA binding in animal models [16][17][18]. Resveratrol also amplifies silent mating type information regulation 1 (SIRT1) gene expression, [18,19] which indirectly inhibitsNF-κB.…”

“…Reactive oxygen species (ROS), bacteria, and inflammatory cytokines activate NF-κB, [14] the pathway specifically linkedto the pathogenesis of UC [12,15,16]. With resveratrol supplementation, NF-κB p65 subunit activity is inhibited through attenuating attenuate nuclear factor of kappa B inhibitor, alpha (IκBα) phosphorylation, IκB kinase beta (IKKβ) activation, extracellular signal-regulated kinases (ERK) phosphorylation, signal transducer and activator of transcription 3 (STAT3) activation and NF-κB DNA binding in animal models [16][17][18].…”