Resveratrol decreases nitric oxide production by hepatocytes during inflammation

Abstract

Introduction The production of excessive amounts of nitric oxide (NO) through inducible nitric oxide synthase (iNOS) contributes to organ injury, inflammation, and mortality after shock. Resveratrol (RSV) is a natural polyphenol that decreases shock-induced hepatic injury and inflammation. We hypothesized that RSV would mediate these effects by reducing hepatocyte iNOS production. Methods Rat hepatocytes were isolated, cultured with varying concentrations of RSV, and then stimulated to induce iNOS with interleukin-1 and interferon. Induction of iNOS protein was measured by western blot, iNOS mRNA by polymerase chain reaction, and NO production was measured by culture supernatant nitrite. Activation of intracellular signaling pathways involving Akt, JNK, and NF-κB were measured by western blot using isoform-specific antibodies. Results RSV significantly reduced the expression of iNOS mRNA, protein, and supernatant nitrite in a dose-dependent manner. Our prior work has demonstrated that Akt and JNK both inhibit hepatic iNOS production, while NF-κB increases iNOS expression. Analysis of signaling pathways in this study demonstrated that RSV increased JNK phosphorylation but decreased Akt phosphorylation and increased NF-κB activation. Conclusion RSV decreases cytokine-induced hepatocyte iNOS expression, possibly through upregulation of the JNK signaling pathway. RSV merits further investigation to determine its mechanism as a compound that can decrease inflammation following shock.

Role of resveratrol in regulation of cellular defense systems against oxidative stress

“…Resveratrol was also found to reduce NO production and iNOS expression through the blockade of IκBα/NF‐κB signaling pathway in lipopolysaccharide‐induced RAW 264.7 cells . Similarly, the induction of NF‐κB‐mediated NO generation as well as iNOS expression in hepatocytes during inflammation was suppressed in the presence of resveratrol (Fig. ).…”

Resveratrol ameliorates renal injury in spontaneously hypertensive rats by inhibiting renal micro-inflammation

“…RSV, a polyphenolic compound found in red wine, has various health beneficial effects through JNK/NF-κB, p38, NO/NOS pathway [ 31 , 32 ]. Li et al [ 33 ] found that RSV can improve renal interstitial fibrosis by specifically inhibiting Smad3 acetylation in unilateral ureteral obstruction mice.…”

Incorporation of lipid nanosystems containing omega-3 fatty acids and resveratrol in textile substrates for wound healing and anti-inflammatory applications

“…Accordingly, the production of excessive amounts of nitric oxide (NO) contributes to inflammation and tissue injury [33]. Regarding this rational, we hypothesized that RSV and omega-3 fatty acids can ameliorate wound healing due to an anti-inflammatory effect by inhibition of NO production, an effect that has been reported in previous studies [34,35]. NLCs presented a NO production inhibition of 64.14 ± 2.08% demonstrating an effect of approximate magnitude of phenylethanoids (NO production inhibition of 6.3-62.3%) that for the extent of NO production inhibition were reported to possess anti-inflammatory properties [36].…”