Resveratrol reduces acute lung injury in a LPS-induced sepsis mouse model via activation of Sirt1

Abstract

The development of acute lung injury (ALI) during sepsis almost doubles the mortality rate of patients. The efficacy of current treatment strategies is low as treatment is usually initiated following the onset of symptoms. Inflammation is one of the main mechanisms of autoimmune disorders and is a common feature of sepsis. The suppression of inflammation is therefore an important mechanism for the treatment of sepsis. Sirtuin 1 (Sirt1) has been demonstrated to play a role in the regulation of inflammation. Resveratrol, a potent Sirt1 activator, exhibits anti‑inflammatory properties. However, the role of resveratrol for the treatment of ALI during sepsis is not fully understood. In the present study, the anti‑inflammatory role of Sirt1 in the lipopolysaccharide (LPS)‑induced TC‑1 cell line and its therapeutic role in ALI was investigated in a mouse model of sepsis. The upregulation of matrix metalloproteinase-9, interleukin (IL)‑1β, IL‑6 and inducible nitric oxide synthase was induced by LPS in the mouse model of sepsis and the TC‑1 cell line, and resveratrol suppressed the overexpression of these proinflammatory molecules in a dose‑dependent manner. Resveratrol decreased pulmonary edema in the mouse model of sepsis induced by LPS. In addition, resveratrol improved lung function and reduced pathological alterations in the mouse model of sepsis. Knockdown of Sirt1 by RNA interference resulted in an increased susceptibility of TC‑1 cells to LPS stimulation and diminished the anti‑inflammatory effect of resveratrol. These results demonstrated that resveratrol inhibits LPS‑induced ALI and inflammation via Sirt1, and indicated that Sirt1 is an efficient target for the regulation of LPS‑induced ALI and inflammation. The present study provides insights into the treatment of ALI during sepsis.

Resveratrol Rescues Kidney Mitochondrial Function Following Hemorrhagic Shock

“…In septic animals, treatment with resveratrol preserved tissue morphology in the lung and kidney (29), mitigated acute lung injury and prevented myocardial depression (17,30). Resveratrol has also been shown to be beneficial in several trauma-hemorrhage models.…”

Anti-inflammatory effect of resveratrol through the suppression of NF-κB and JAK/STAT signaling pathways

“…It possesses antiinflammatory and anti-oxidant properties [12]. A growing body of in vitro and in vivo evidence suggests that resveratrol acts through multiple pathways, and reduces the inflammatory reaction in diseases such as type 2 diabetes [21], acute lung injury [22], and atherosclerosis [23]. LPS is a major component of the cell wall of Gram-negative bacteria.…”

Resveratrol enhanced FOXO3 phosphorylation via synergetic activation of SIRT1 and PI3K/Akt signaling to improve the effects of exercise in elderly rat hearts

“…Resveratrol is also a SIRT1 activator (Frazzi et al 2013;Lakshminarasimhan et al 2013;Li et al 2013). When SIRT1 is activated, SIRT1 will block FOXO3 accumulation in the nucleus and inhibit cell death.…”

“…SIRT1 is a deacetylase that can remove the acetyl group from FOXO3 and NFκB (Frazzi et al 2013;Lakshminarasimhan et al 2013;Li et al 2013). …”