Resveratrol attenuates inflammation in the rat heart subjected to ischemia-reperfusion: Role of the TLR4/NF-κB signaling pathway

Abstract

Abstract. It has been previously reported that Toll-like receptor 4 (TLR4)/NF-κB signaling mediates early inflammation during myocardial ischemia and reperfusion. It has additionally been suggested that resveratrol produces cardioprotective and anti-inflammatory effects. The aim of the present study was to investigate whether resveratrol could modulate TLR4/NF-κB signaling, reduce neutrophil accumulation and TNF-α induction in an ischemia/reperfusion injured rat heart model. Rats were randomly exposed to a sham operation, myocardial ischemia and reperfusion (MI/R), MI/R + resveratrol or MI/R + resveratrol + L-NAME. The data showed that following MI/R, the expression of myocardial TLR4 and NF-κB increased significantly in the area of induced ischemia. As compared with MI/R, resveratrol significantly attenuated the expression of TLR4 and NF-κB and reduced the levels of myeloperoxidase, serum and myocardial TNF-α production, myocardial infarct size and myocardial apoptosis induced by MI/R. All the effects of resveratrol were abolished upon application of L-NAME, a nitric oxide (NO) synthase inhibitor. These data provide evidence that resveratrol inhibits TLR4/NF-κB signaling in the rat heart subjected to MI/R, and the anti-inflammatory effect of resveratrol is associated with NO production.

Resveratrol Attenuates Acute Inflammatory Injury in Experimental Subarachnoid Hemorrhage in Rats via Inhibition of TLR4 Pathway

“…Thus far, although previous study reported that RSV could reduce neuroinflammation after SAH [22], the molecular mechanisms underlying RSV-dependent anti-inflammatory effects remain obscure. Accumulating studies indicated that RSV could inhibit the activation of TLR4 and the subsequent downstream signaling pathways in different fields [24,25,26]. Thus, we designed this study to confirm the hypothesis that RSV could attenuate SAH-induced EBI by modulating the TLR4 signaling pathway.…”

“…Most importantly, mountain evidence have demonstrated the critical role of the TLR4 signaling pathways on initiating an inflammatory response after SAH, and that inhibition of the TLR4 signaling pathways could attenuate microglia-induced neuroinflammation [14,15,30]. Regarding the relationship between RSV and TLR4, accumulating studies indicated that RSV could regulate the TLR4 pathway both in vivo and in vitro [24,26,38,39]. For example, Byun et al (2015) reported that RSV could negatively regulate lipopolysaccharides (LPS)-induced NF-κB signaling through TLR4 in macrophages [26].…”

Cardioprotective effect of miRNA-22 on hypoxia/reoxygenation induced cardiomyocyte injury in neonatal rats

“…Numerous studies have demonstrated that MI/R could lead to cardiomyocyte damage by complex pathophysiological mechanisms, including inflammation (Wang et al, 2012), apoptosis (Xu et al, 2011), free radical formation (Li et al, 2015), calcium overload (Carvajal et al, 1999), platelet aggregation and so on. Currently, most therapy research has been aimed at one aspect of these complicated mechanisms.…”

Resveratrol Alleviates Inflammatory Responses and Oxidative Stress in Rat Kidney Ischemia-Reperfusion Injury and H2O2-Induced NRK-52E Cells via the Nrf2/TLR4/NF-κB Pathway

“…RSV has been shown to regulate the expression of TLR4, enhance the expression of Nrf2, and inhibit the activity of caspase-3 in cardiac and hepatic IRI [27-29]. Moreover, the protective effects of RSV have been demonstrated in many kidney diseases such as diabetic nephropathy, aldosterone-induced kidney injury, aging kidney, and even renal IRI [30], but the mechanism underlying its renoprotective effect remains unclear.…”