Therapeutic Efficacy Of Resveratrol Research Articles

Recent progress in nanotechnology-based drug carriers for resveratrol delivery

Resveratrol is a polyphenol with diverse pharmacological activities, but its clinical efficacy is limited due to low solubility/permeability, light-induced isomerization, auto-oxidation, and rapid metabolism. Nanodelivery systems, such as liposomes, polymeric nanoparticles, lipid nanocarriers, micelles, nanocrystals, inorganic nanoparticles, nanoemulsions, protein-based nanoparticles, exosomes, macrophages, and red blood cells (RBCs) have shown great potential for improving the solubility, biocompatibility, and therapeutic efficacy of resveratrol. This review comprehensively summarizes the recent advances in resveratrol nanoencapsulation and describes potential strategies to improve the pharmacokinetics of existing nanoformulations, enhance targeting, reduce toxicity, and increase drug release and encapsulation efficiency. The article also suggests that in order to avoid potential safety issues, resveratrol nanoformulations must be tested in vivo in a wide range of diseases.

Amelioration of experimental nephrotoxicity due to 5-Flourouracil by Resveratrol in comparison to Vitamin-E

The therapeutic efficacy of Resveratrol (RSV) and Vitamin E were studied against 5-Flourouracil (5-FU) induced nephrotoxicity. 36 male Wistar rats were selected randomly weighing between 150-180 g and are made into 6 groups, each group containing 6 rats. Group 1 was maintained as sham. 5-Flourouracil was administered to groups 2, 5 and 6 intraperitoneally (20 mg/kg body weight) on day 1, 3 and 7. Group 2 was kept as positive control (administered 5-FU intraperitoneally). Groups 3, 5 and 4, 6 were administered vitamin E and resveratrol per orally for 14 days @ 200 mg/kg bwt. At the end of the experiment the blood was withdrawn and serum analyzed for renal biomarkers. For histopathological studies, samples of kidney tissue collected by inducing euthanasia in rats. The sero-biochemical analysis revealed a significant increase in BUN and creatinine values of the rats in group 2. The antioxidant activity was analyzed and the rats in group 2 revealed a significant rise in the values of protein carbonyl, TBARS and significant decrease in GSH. Group 2 also showed an increase in TNF-α and decrease in interleukin-10 concentration. Sections of kidney tissue collected from group 2 showed marked dilation and elongation of tubules, moderate infiltration with inflammatory cells degeneration of bowman’s capsule and tubular congestion. Comparatively, groups undergone treatment showed amelioration in the parameters. Thus, resveratrol and vitamin-E exert protective actions against 5-flourouracil (5-FU) induced nephrotoxicity.

Resveratrol provides benefits in mice with type II diabetes-induced chronic renal failure through AMPK signaling pathway.

Type II diabetes-induced ischemic injuries are known to lead to the rapid degeneration of the kidneys as a result of chronic renal failure. Chronic renal failure is a condition, which typically manifests with symptoms including cardiovascular system and left ventricular hypertrophy, atherosclerosis as well as arterial and aortic stiffness. Resveratrol is a multifunctional compound that has been reported to produce beneficial outcomes for patients with type-II diabetes due to prevention of oxidative stress and apoptosis. However, the beneficial effects of resveratrol in chronic renal failure and the underlying mechanisms have remained to be fully elucidated. The present study investigated the therapeutic effects of resveratrol in mice with chronic renal failure induced by type-II diabetes and assessed the mechanism of action. Oxidative stress, apoptosis and adenosine monophosphate-activated protein kinase (AMPK) in the renal cells of the model mice were assessed. Changes in inflammatory factors renal cells from experimental mice as well as insulin resistance were also analyzed. Morphological changes and immunocytes in renal cells were determined by immunostaining. The results demonstrated that resveratrol treatment decreased the apoptotic rate of renal cells from experimental mice. Oxidative stress also improved in renal cells, as indicated by inhibition of superoxide dismutase and reduced glutathione and 4-hydroxy-2-nonenal levels. In addition, insulin resistance was improved after an 8-week treatment with resveratrol. Inflammatory factors were decreased and factors promoting kidney function were increased after resveratrol treatment. Furthermore, morphological changes were observed to be ameliorated, indicating the therapeutic efficacy of resveratrol. In addition, immunocyte precipitation in renal cells was markedly decreased in resveratrol-treated mice. Importantly, the AMPK signaling pathway was found to be involved in the beneficial effect of resveratrol on the model mice. In conclusion, the present study suggested that resveratrol may be an ideal agent for the treatment of chronic renal failure induced by type-II diabetes through regulation of the AMPK signaling pathway, which should be further investigated in clinical trials.

Evaluation of growth inhibitory response of Resveratrol and Salinomycin combinations against triple negative breast cancer cells.

Resveratrol (RSVL) a dietary phytochemical showed to enhance the efficacy of chemotherapeutic drugs. Recently, Salinomycin (SAL) has gained importance as cancer therapeutic value for breast cancer (BC), however, its superfluxious toxicity delimits the utility. Taking the advantage of RSVL, the therapeutic efficacy of RSVL and SAL combination was studied in vitro and in vivo system. Firstly, the synergistic combination dose of RSVL and SAL was calculated and further, the efficacy was examined by wound healing, and Western blots analysis. Further, in vivo study was performed to confirm the effect of colony formation and apoptosis detection by flow cytometry based assays. Further, the molecular mode of action was determined at both transcript and translational level by quantitative Real Time PCR combination in Ehrlich ascitic carcinoma model.The combination of IC20 (R20) of RSVL and IC10 (S10) dose of SAL showed best synergism (CI<1) with ∼5 fold dose advantage of SAL. Gene expression results at mRNA and protein level revealed that the unique combination of RSVL and SAL significantly inhibited epithelial mesenchymal transition (Fibronectin, Vimentin, N-Cadherin, and Slug); chronic inflammation (Cox2, NF-kB, p53), autophagy (Beclin and LC3) and apoptotic (Bax, Bcl-2) markers. Further, i n vivo study showed that low dose of SAL in combination with RSVL increased life span of Ehrlich ascitic mice. Overall, our study revealed that RSVL synergistically potentiated the anticancer potential of SAL against triple negative BC.

Chronic treatment with resveratrol, a natural polyphenol found in grapes, alleviates oxidative stress and apoptotic cell death in ovariectomized female rats subjected to chronic cerebral hypoperfusion

Objectives: Resveratrol appears to have neuroprotective potential in various animal models of brain disorders including cerebral ischemia and neurodegenerative diseases. Chronic cerebral hypoperfusion is a well-known pathological condition contributing to the neurodegenerative diseases such as vascular dementia. Purpose of the present study is to evaluate the possible therapeutic potential of resveratrol in a model of vascular dementia of ovariectomized female rats. Assessment of the potential was based on the determination of brain oxidative status, caspase-3 level, glial fibrillary acidic protein (GFAP), and neuronal damage on hippocampus and cerebral cortex.Methods: For creating the model of chronic cerebral hypoperfusion, ovariectomized female Wistar rats were subjected to the modified two vessel occlusion method, with the right common carotid artery being occluded first and the left one a week later.Results: At the 15th day following the ligation, neuronal damage was accompanied by the increased immunoreactivities of both GFAP and caspase-3, and significant neurodegeneration was evident in the hippocampus and cortex, all of which were significantly alleviated with resveratrol treatment (10 mg/kg). Biochemical analysis revealed that the resveratrol treatment decreased lipid peroxidation and restored reduced glutathione level as well.Discussion: The collected data of the present study suggest that the administration of resveratrol may provide a remarkable therapeutic benefit for vascular dementia, which is most likely related to the prevention of both apoptotic cell death and oxidative stress. We believe that therapeutic efficacy of resveratrol deserves to be tested for potential clinical application in postmenopausal elderly women suffering from vascular dementia.

Resveratrol protects primary cortical neuron cultures from transient oxygen-glucose deprivation by inhibiting MMP-9

It was recently shown that resveratrol exerts neuroprotective effects against cerebral ischemia in mice. The aim of the present study was to further confirm these effects in in vitro primary cortical neuron cultures with transient oxygen-glucose deprivation (OGD), and to investigate whether these effects are due to the inhibition of matrix metalloproteinase-9 (MMP-9) and of cell apoptosis. Neuronal primary cultures of cerebral cortex were prepared from BALB/c mice embryos (13-15 days). Cells from 14- to 16-day cultures were subjected to OGD for 3 h, followed by 21 h of reoxygenation to simulate transient ischemia. Different doses of resveratrol were added into the culture medium during the simulation of transient ischemia. The effect of the extracellular signal-regulated kinase (ERK) inhibitor U0126 was studied by adding U0126 (5 µg/µl, 4 µl) into the culture medium during transient ischemia; as a control, we used treatment of cells with 50 µM of resveratrol. Cell viability was investigated using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) reduction assay. Cell apoptosis was assessed by flow cytometry. The effects of resveratrol on the expression of MMP-9 were analyzed by western blotting and reverse transcription-polymerase chain reaction (RT-PCR), while the levels of ERK, phosphorylated (p)-ERK, cleaved caspase-3, Bax and Bcl-2 were measured by western blotting. The results of the MTT assay showed that cell viability is significantly reduced by transient OGD. OGD induced cell apoptosis, the expression of Bax and the activation of caspase-3 and ERK, inhibited the expression of Bcl-2 and increased the expression of MMP-9, while these effects were reversed by treatment with resveratrol. The therapeutic efficacy of resveratrol was shown to be dose-dependent, with the most suitable dose range determined at 50-100 µM. Treatment with U0126 inhibited MMP-9 and Bax expression and caspase-3 activation, while it further promoted the expression of the anti-apoptotic molecule Bcl-2, suggesting that resveratrol inhibits MMP-9 expression and cell apoptosis by attenuating the activation of ERK1/2. In conclusion, OGD can induce apoptosis through canonical apoptotic signals and by regulating the expression of MMP-9; the anti-apoptotic activity of resveratrol and its inhibitory effect on MMP-9 expression contribute in the reduced activation of ERK.

Electrophysiological protective and therapeutic efficacy of resveratrol against cadmium chloride: An in vitro study

Resveratrol (trans-3,4',5-trihydroxystilbene- RES), is a natural antioxidant found in variousfruits and vegetables and is abundant in grapes. It has beneficial effects against coronary heartdiseases. This study aims to explore the protective and therapeutic effects of resveratrol oncadmium chloride induced toxicity on isolated toad's hearts. Electrocardiogram (ECG) wasrecorded before and after direct perfusion of cadmium chloride (CdCl2) and resveratrol.Application of CdCl2 (2mM/L) into isolated toad's heart significantly decreased the heart rate(HR) accompanied by an elongation in the conduction time (P-R interval), while a nonsignificant decrease of the ventricular contraction (R-wave amplitude) was observed withinminutes (5-30 min) of CdCl2 application into isolated toad's. Pretreatment of isolated toad'shearts with RES (21μM/L) five min before CdCl2 application abolished the severe bradycardiaand negative inotropic effect induced by CdCl2, this was accompanied by improvement ofcardiac disorders induced by this toxic heavy metal. While, post treatment of RES afterappearance of cardiac abnormalities induced by CdCl2 didn’t affect these induced disorders. Inconclusion, the obtained investigation indicates that RES could serve as a protective agentagainst some of acute ( CdCl2) toxicity on isolated toad's heart than more that its therapeuticefficacy. However, low level of resveratrol at was not effective in preventing either neither severbradycardia nor in reducing ventricular dysfunction induced by cadmium.

Neuroprotective mode of action of resveratrol in central nervous system

Resveratrol has gained importance as a naturally available medicine for the prevention of inflammatory and neurodegenerative diseases. In addition to its antioxidant properties, resveratrol also plays a significant role in neuronal differentiation through activation of SIRT1 and SIRT3. However, the receptor-mediated intracellular signal induced by resveratrol is yet to be determined. The mode of action of resveratrol presumably involves transcriptional regulation of the NF-κB family of proteins. It may also interact with the nuclear hormone receptor family, which includes estrogen receptors and vitamin D receptors in the brain. We found that resveratrol-enriched grape extract prevents paraquat-induced damage of hippocampal neurons and has the least effect on hippocampal cell damage. In this review article, we discuss the perspectives on therapeutic efficacy of resveratrol and its mode of action in neuronal cell growth and differentiation following brain inflammation and neurodegeneration.

Expression of integrin in hepatic fibrosis and intervention of resveratrol

The aim of this study was to explore the expression of integrin-β1 in different stages of hepatic fibrosis and intervention of resveratrol as well as the way by which integrin-β1 promoted hepatic fibrosis. Hepatic fibrosis models of male Sprague Dawley (SD) rats were created and intragastric administration of resveratrol was given in low (40 mg/kg), middle (120 mg/kg) and high (200 mg/kg) dose groups. The expression of integrin-β1, transforming growth factor-β (TGF-β) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in different stages of hepatic fibrosis was detected by using RT-PCR. The expression of hexadecenoic acid (HA) and precollagen III (pc III) was assayed by radioimmunoassay. The expression of integrin-β1, TGF-β and TIMP-1 was determined in each group. Liver function and pathological sections of each group in different stages of hepatic fibrosis was tested to judge the therapeutic efficacy of resveratrol at different doses. The expression of integrin-β1 in normal control group was low and steady and was not increased with the development of hepatic fibrosis, but it was increased in other groups. The expression levels of integrin-β1 in the model control group (0.878 ± 0.03, P 0.05). The expression levels of integrin-β1 and TGF-β in middle dose group and high dose group were higher than other groups (P<0.01). The expression levels of integrin-β1 and TGF-β in model control group and low dose group were lower than the normal control group (P<0.01). The expression levels of TIMP-1 in the model control and low dose groups were higher than the other groups (P<0.01). The expression levels of TIMP-1 in the middle dose group and the high dose group were lower than the normal control group (P<0.01). The expression of integrin-β1 existed in all stages of hepatic fibrosis of SD rats, and it was increased with the development of hepatic fibrosis. The expression of TGF-β and TIMP-1 was consistent with that of integrin-β1 in different stages of hepatic fibrosis. Resveratrol could improve the degree of hepatic fibrosis of SD rats and decrease the expression of integrin-β1 markedly at a dose of 120 mg/kg.