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Cervical cancer affects many women worldwide, with more than 500,000 cases diagnosed and approximately 300,000 deaths each year. Resveratrol is a natural substance of the class of phytoalexins with a basic structure of stilbenes and has recently drawn scientific attention due to its anticancer properties. The purpose of this review is to examine the effectiveness of resveratrol against cervical cancer. All available in vitro and in vivo studies on cervical cancer were critically reviewed. Many studies utilizing cervical cancer cells in culture reported a reduction in proliferation, cell cycle arrest, and induction of apoptosis. Apart from apoptosis, induction of autophagy was seen in some studies. Importantly, many studies have shown a reduction in the HPV oncoproteins E6 and E7 and increased levels of the tumor suppressor p53 with resveratrol treatment. A few studies examined the effects of resveratrol administration in mice ectopic-xenografted with cervical cancer cells showing reduced tumor volume and weight. Overall, the scientific data show that resveratrol has the ability to target/inhibit certain signaling molecules (EGFR, VEGFR, PKC, JNK, ERK, NF-kB, and STAT3) involved in cervical cancer cell proliferation and survival. Further in vivo experiments and clinical studies are required to better understand the potential of resveratrol against cervical cancer.

Insulin resistance, a main characteristic of type 2 diabetes mellitus (T2DM), is linked to obesity and excessive levels of plasma free fatty acids (FFA). Studies indicated that significantly elevated levels of FFAs lead to skeletal muscle insulin resistance, by dysregulating the steps in the insulin signaling cascade. The polyphenol resveratrol (RSV) was shown to have antidiabetic properties but the exact mechanism(s) involved are not clearly understood. In the present study, we examined the effect of RSV on FFA-induced insulin resistance in skeletal muscle cells in vitro and investigated the mechanisms involved. Parental and GLUT4myc-overexpressing L6 rat skeletal myotubes were used. [ 3 H]2-deoxyglucose (2DG) uptake was measured, and total and phosphorylated levels of specific proteins were examined by immunoblotting. Exposure of L6 cells to FFA palmitate decreased the insulin-stimulated glucose uptake, indicating insulin resistance. Palmitate increased ser 307 (131% ± 1.84% of control, p < 0.001) and ser 636/639 (148% ± 10.1% of control, p < 0.01) phosphorylation of IRS-1, and increased the phosphorylation levels of mTOR (174% ± 15.4% of control, p < 0.01) and p70 S6K (162% ± 20.2% of control, p < 0.05). Treatment with RSV completely abolished these palmitate-induced responses. In addition, RSV increased the activation of AMPK and restored the insulin-mediated increase in (a) plasma membrane GLUT4 glucose transporter levels and (b) glucose uptake. These data suggest that RSV has the potential to counteract the FFA-induced muscle insulin resistance.

Insulin resistance, the hallmark of type 2 diabetes mellitus (T2DM), is linked to hyperinsulinemia, which develops to counterbalance initial peripheral hormone resistance. Studies indicate that chronically elevated levels of insulin lead to skeletal muscle insulin resistance by deregulating steps within the insulin signaling cascade. The polyphenol resveratrol (RSV) has been shown to have antidiabetic properties in vitro and in vivo. In the present study, we examined the effect of RSV on high insulin (HI)-induced insulin resistance in skeletal muscle cells in vitro and investigated the mechanisms involved. Parental and GLUT4myc-overexpressing L6 rat skeletal muscle cells were used. [ 3 H]2-deoxyglucose (2DG) uptake was measured, and total and phosphorylated levels of specific proteins were examined by immunoblotting. Exposure of L6 cells to HI levels (100 nM) for 24 h decreased the acute-insulin-stimulated 2DG uptake, indicating insulin resistance. HI increased ser 307 and ser 636/639 phosphorylation of IRS-1 (to 184% ± 12% and 225% ± 28.9% of control, with p < 0.001 and p < 0.01, respectively) and increased the phosphorylation levels of mTOR (174% ± 6.7% of control, p < 0.01) and p70 S6K (228% ± 33.5% of control, p < 0.01). Treatment with RSV abolished these HI-induced responses. Furthermore, RSV increased the activation of AMPK and restored the insulin-mediated increase in plasma membrane GLUT4 glucose transporter levels. These data suggest that RSV has a potential to counteract the HI-induced muscle insulin resistance.

We have shown that both insulin and resveratrol (RSV) decrease neointimal hyperplasia in chow-fed rodents via mechanisms that are in part overlapping and involve the activation of endothelial nitric oxide synthase (eNOS). However, this vasculoprotective effect of insulin is abolished in high-fat-fed insulin-resistant rats. Since RSV, in addition to increasing insulin sensitivity, can activate eNOS via pathways that are independent of insulin signaling, such as the activation of sirtuin 1 (SIRT1) and AMP-activated kinase (AMPK), we speculated that unlike insulin, the vasculoprotective effect of RSV would be retained in high-fat-fed rats. We found that high-fat feeding decreased insulin sensitivity and increased neointimal area and that RSV improved insulin sensitivity (p < 0.05) and decreased neointimal area in high-fat-fed rats (p < 0.05). We investigated the role of SIRT1 in the effect of RSV using two genetic mouse models. We found that RSV decreased neointimal area in high-fat-fed wild-type mice (p < 0.05), an effect that was retained in mice with catalytically inactive SIRT1 (p < 0.05) and in heterozygous SIRT1-null mice. In contrast, the effect of RSV was abolished in AMKPα2-null mice. Thus, RSV decreased neointimal hyperplasia after arterial injury in both high-fat-fed rats and mice, an effect likely not mediated by SIRT1 but by AMPKα2., (© 2020 The Author(s) Published by S. Karger AG, Basel.)

Different diseases and disorders that affect the kidneys include, but are not limited to, glomerulonephritis, diabetic nephropathy, polycystic kidney disease, kidney stones, renal fibrosis, sepsis, and renal cell carcinoma. Kidney disease tends to develop over many years, making it difficult to identify until much later when kidney function is severely impaired and undergoing kidney failure. Although conservative care, symptom management, medication, dialysis, transplantation, and aggressive renal cancer therapy are some of the current strategies/approaches to kidney disease treatment, new preventative targeted therapies are needed. Epidemiological studies have suggested that a diet rich in fruits and vegetables is associated with health benefits including protection against kidney disease and renal cancer. Resveratrol, a polyphenol found in grapes and berries, has been reported to have antioxidant, anti-inflammatory, antidiabetic, hepatoprotective, neuroprotective, and anti-cancer properties. The current review summarizes the existing in vitro and in vivo animal and human studies examining the nephroprotective effects of resveratrol.

Background: There is evidence that sirtuin 1 (SIRT1), a key regulator of nutrient metabolism, increases β-cell secretory function. Excess circulating fat, as seen in obesity, has been shown to decrease β-cell function, an effect that may involve decreased SIRT1 activity. Consequently, SIRT1 activation may increase β-cell function in conditions of elevated plasma-free fatty acid levels. Here we attempted to attenuate the lipid-induced decrease in β-cell function in vivo using pharmacological and genetic models of SIRT1 activation., Methods: Our pharmacologic model involved 48 h intravenous infusion of Wistar rats with either saline or oleate with or without the SIRT1 activator resveratrol. Additionally, we used β-cell-specific SIRT1 overexpressing (BESTO) mice and wild-type littermates infused for 48 h intravenously with either saline or oleate. In both models, the infusion period was followed by assessment of β-cell function using the hyperglycemic clamp method., Results: Lipid infusion resulted in a significant decrease in β-cell function as expected in both rats (p < 0.05) and mice (p < 0.001). Both models of SIRT1 activation, which did not alter β-cell function in the absence of fat, resulted in partial protection from the fat-induced decrease in β-cell function (NS vs. control)., Conclusion: These results suggest that SIRT1 is a therapeutic target in decreased β-cell function specifically induced by fat.

Uncontrolled cell growth and resistance to apoptosis characterize cancer cells. These two main features are initiated in cancer cells through mutations in key signaling molecules, which regulate pathways that are directly involved in controlling cell proliferation and apoptosis. Resveratrol (RSV), a naturally occurring plant polyphenol, has been shown to have biological effects counteracting different diseases. It has been found to provide cardio-protective, neuro-protective, immuno-modulatory, and anti-cancer health benefits. RSV has been found to inhibit cancer cell proliferation, induce cell cycle arrest and apoptosis, and these anticancer effects may be due to its ability to modulate signaling molecules involved in these processes. The present review summarizes the existing in vitro and in vivo studies on resveratrol and its anti-lung cancer properties. [ABSTRACT FROM AUTHOR]

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Atherosclerotic cardiovascular disease is a leading cause of morbidity and mortality worldwide and revascularization procedures used for treatment often result in restenosis. Resveratrol (RSV), a red wine polyphenol, inhibits low-density lipoprotein-oxidation, suppresses smooth muscle cell (SMC) proliferation, and in more recent studies, enhances the expression of endothelial nitric oxide synthase (eNOS), which can decrease SMC migration, however the majority of these studies were performed in vitro. We hypothesized that RSV may decrease SMC migration and proliferation in vivo, resulting in reduced neointimal growth after carotid artery balloon injury, an established model of restenosis. RSV treatment was given to male Sprague-Dawley rats at a subcutaneous (s.c.) dose of 4mgkg-[sup -1]day[sup -1] for 3 days before arterial injury and was continued after injury. A control group was also studied. Carotid arteries were collected at 4, 14, and 28 days after balloon injury. RSV significantly reduced intimal area by 50% at 28 days (n=8, P<0.01) and decreased intimal SMC proliferation by 45% (BrdU-labeling) at 14 days (n=7, P<0.05) after vessel injury compared to control. Interestingly, RSV also strongly inhibited SMC migration by 77% at 4 days after balloon injury (n=4, P<0.05). This effect was not blocked by co-treatment with the NOS inhibitor N-Nitro-L-arginine methyl ester (L-NAME) (2mgkg[sup -1]day[sup -1]; s.c.) (n=4), indicating an NO-independent effect of RSV. This is the first demonstration of RSV decreasing SMC proliferation and migration in vivo, resulting in an inhibition of neointimal growth. These results support an anti-atherogenic role for RSV and raise the possibility that RSV may have clinical potential in the prevention and treatment of restenosis after angioplasty. [ABSTRACT FROM AUTHOR]

Abstract: Revascularization procedures used for treatment of atherosclerosis often result in restenosis. Resveratrol (RSV), an antioxidant with cardiovascular benefits, decreases neointimal formation after arterial injury by a mechanism that is still not fully clarified. Our main objective was to address the role of nitric oxide synthases (NOSes) and more specifically the endothelial-NOS (eNOS) isoform as a mediator of this effect. RSV (4mg/kg/day, s.c.) alone or in combination with the NOS inhibitor N-nitro-l-arginine methyl ester (l-NAME) (2mg/kg/day, s.c.) was given to Sprague-Dawley rats beginning at 3 days before arterial (carotid or aortic) injury. RSV reduced neointimal formation by 50% (P <0.01), decreased intimal cell proliferation by 37% (P <0.01) and reduced inflammatory markers such as PECAM and MMP-9 mRNA. These effects of RSV were all abolished by coadministration of l-NAME. Oral RSV (beginning at 5 days before arterial injury) reduced neointimal thickness after femoral wire injury in mice, however this effect was not observed in eNOS knockout mice. This is the first report of RSV decreasing neointimal cell proliferation and neointimal growth through an eNOS-dependent mechanism. [Copyright &y& Elsevier]

Abstract: Although recent studies in vitro and in vivo indicate that the polyphenol resveratrol (RSV) has anti-diabetic properties, the exact mechanisms involved are not known. In the present study, we examined the effects of RSV and the mechanism of regulation of glucose uptake in skeletal muscle cells. In L6 myotubes RSV (100μM) induced maximum stimulation of glucose (2DG) uptake (201±8.90% of control, p <0.001), an effect that was similar to insulin action. RSV-stimulated glucose uptake was abolished by AMPK inhibition. In the presence of the sirtuin inhibitor nicotinamide, RSV-stimulated 2DG uptake and AMPK phosphorylation were abolished. RSV did not stimulate significant translocation of GLUT4 or GLUT1 transporters. However, treatment with indinavir, a GLUT4 specific inhibitor, blocked RSV-stimulated glucose uptake. We propose that RSV elevates glucose uptake in muscle cells through a mechanism that involves sirtuins and AMPK and possibly stimulation of GLUT4 transporter intrinsic activity. [Copyright &y& Elsevier]