Effect of resveratrol supplementation on hepatic steatosis and cardiovascular indices in overweight subjects with type 2 diabetes: a double-blind, randomized controlled trial.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are prone to develop non-alcoholic fatty liver disease (NAFLD) and cardiovascular diseases (CVD). We aimed to investigate whether the resveratrol supplementation improves novel hepatic and cardiovascular indices in these patients. METHODS: We conducted a double-blind, randomized controlled trial for 8 weeks. Seventy-six patients with T2DM were randomly assigned to receive 1000 mg/day resveratrol or placebo. Levels of lipid accumulation product (LAP), visceral adiposity index (VAI), Castelli risk index I (CRI-I), CRI-II and atherogenic coefficient (AC) were measured at the beginning and after intervention. RESULTS: A total of 71 participants completed the trial. After adjusting for confounding factors including medications, diabetes duration, energy intake and physical activity, no significant difference was found between the intervention group and the control group in LAP (mean change: - 2.46 ± 23.3 vs. 1.43 ± 14.3; P = 0.43), VAI (mean change: - 0.25 ± 1.1 vs. - 0.02 ± 0.6; P = 0.47), CRI-I (mean change: - 0.25 ± 0.9 vs. - 0.09 ± 0.5; P = 0.79), CRI-II (mean change: - 0.23 ± 0.7 vs. - 0.06 ± 0.6; P = 0.38) and AC (mean change: - 0.25 ± 0.9 vs. - 0.09 ± 0.5; P = 0.79). CONCLUSIONS: Resveratrol supplementation had no effect on hepatic steatosis and cardiovascular indices. Further clinical trials, especially among subjects with dyslipidemia are needed to reach a firm conclusion. In addition, taking all medications should be controlled in future studies. Trial registration The protocol was registered on 29/12/2017 at the Iranian clinical trials website (IRCT20171118037528N1) with URL: https://en.irct.ir/trial/27734 .

Resveratrol Adjunct Therapy for Negative Symptoms in Patients With Stable Schizophrenia: A Double-Blind, Randomized Placebo-Controlled Trial.

BACKGROUND: Patients with schizophrenia can generally manifest a broad variety of primary negative symptoms. The current study aimed to assess the efficacy and tolerability of resveratrol add-on therapy in the treatment of negative symptoms in patients with stable schizophrenia. METHODS: In a randomized, double-blind, and placebo-controlled setting, schizophrenia patients were assigned to receive either 200 mg/d resveratrol or matched placebo in addition to a stable dose of risperidone for 8 weeks. Patients were assessed using the positive and negative syndrome scale, the extrapyramidal symptom rating scale, and Hamilton Depression Rating Scale over the trial period. The primary outcome was considered as the change in positive and negative subscale score from baseline to week 8 between the treatment arms. RESULTS: A total 52 patients completed the trial (26 in each arm). Baseline characteristics of both groups were statistically similar (P > .05). Despite the statistically similar behavior of positive symptoms between the groups across time (Greenhouse-Geisser corrected: F = 1.76, df = 1.88, P = .180), the resveratrol group demonstrated greater improvement in negative, general psychopathology, and total scores (Greenhouse-Geisser corrected: F = 12.25, df = 2.04, P < .001; F = 5.42, df = 1.56, P = .011; F = 7.64, df = 1.48, P = .003). HDRS scores and its changes, ESRS score, and frequency of other complications were not significantly different between resveratrol and placebo groups. CONCLUSION: Adding resveratrol to risperidone can exhibit remarkable efficacy and safety in terms of management of schizophrenia-related negative symptoms.

Potential enhancement of host immunity and anti-tumor efficacy of nanoscale curcumin and resveratrol in colorectal cancers by modulated electro- hyperthermia.

BACKGROUND: Modulated electro-hyperthermia (mEHT) is a form of hyperthermia used in cancer treatment. mEHT has demonstrated the ability to activate host immunity by inducing the release of heat shock proteins, triggering apoptosis, and destroying the integrity of cell membranes to enhance cellular uptake of chemo-drugs in tumor cells. Both curcumin and resveratrol are phytochemicals that function as effective antioxidants, immune activators, and potential inhibitors of tumor development. However, poor bioavailability is a major obstacle for use in clinical cancer treatment. METHODS: This purpose of this study was to investigate whether mEHT can increase anti-cancer efficacy of nanosized curcumin and resveratrol in in vitro and in vivo models. The in vitro study included cell proliferation assay, cell cycle, and apoptosis analysis. Serum concentration was analyzed for the absorption of curcumin and resveratrol in SD rat model. The in vivo CT26/BALB/c animal tumor model was used for validating the safety, tumor growth curve, and immune cell infiltration within tumor tissues after combined mEHT/curcumin/resveratrol treatment. RESULTS: The results indicate co-treatment of mEHT with nano-curcumin and resveratrol significantly induced cell cycle arrest and apoptosis of CT26 cells. The serum concentrations of curcumin and resveratrol were significantly elevated when mEHT was applied. The combination also inhibited the growth of CT26 colon cancer by inducing apoptosis and HSP70 expression of tumor cells while recruiting CD3+ T-cells and F4/80+ macrophages. CONCLUSIONS: The results of this study have suggested that this natural, non-toxic compound can be an effective anti-tumor strategy for clinical cancer therapy. mEHT can enable cellular uptake of potential anti-tumor materials and create a favorable tumor microenvironment for an immunological chain reaction that improves the success of combined treatments of curcumin and resveratrol.

Resveratrol as adjunctive therapy in treatment of irritability in children with autism: A double-blind and placebo-controlled randomized trial.

WHAT IS KNOWN AND OBJECTIVE: The underlying pathophysiology of autism spectrum disorder (ASD) has been linked to immune dysregulation, oxidative stress and excitation-inhibition imbalance. Among associated symptoms of ASD, management of irritability has gained considerable attention as it complicates adjustment of ASD patients and thus necessitates its pharmacological treatment. Resveratrol is a plant phytoalexin, which has been demonstrated to have neuroprotective effects through its anti-inflammatory and antioxidant properties. This double-blind, placebo-controlled randomized trial was designed to assess the potential therapeutic effects of resveratrol plus risperidone on irritability of ASD patients. METHODS: Sixty-two patients were assigned randomly into two groups of resveratrol and placebo. Both groups were treated with risperidone twice daily starting at a dose of 0.5 mg with a dose increase of 0.5 mg per week (for the first 3 weeks). Resveratrol dosage was 250 mg twice per day from the beginning of the study. Using the Aberrant Behavior Checklist-Community (ABC-C), patients were assessed for ASD-related behavioural symptoms at baseline, week 5 and week 10. The frequency of adverse events was recorded using a checklist containing 25 possible side effects, including general, gastrointestinal, neurological and cardiovascular complications. RESULTS AND DISCUSSION: Improvements in primary outcome measure (irritability) and three secondary outcome measures (lethargy/social withdrawal, stereotypic behaviour and inappropriate speech subscales) in the resveratrol group were statistically similar to those in the placebo group. The repeated measures analysis showed no time × treatment interaction on these subscale scores. In contrast, patients in the resveratrol group showed greater decline in hyperactivity/non-compliance score as a secondary outcome measure (mean difference [CI = 95%] = 4.51 [0.10-8.92], t = 2.04; P = .04), and repeated measures analysis showed significant effect for time × treatment effect on this subscale score (F = 3.81; df = 1.30; P = .043). There was no significant difference in number and severity of adverse events between the two groups. WHAT IS NEW AND CONCLUSION: This clinical trial demonstrated no significant effect for adjunctive treatment with resveratrol on irritability of patients with ASD. However, it provided preliminary evidence indicating that resveratrol could improve hyperactivity/non-compliance of ASD patients.

Potential Adverse Effects of Resveratrol: A Literature Review.

Due to its health benefits, resveratrol (RE) is one of the most researched natural polyphenols. Resveratrol's health benefits were first highlighted in the early 1990s in the French paradox study, which opened extensive research activity into this compound. Ever since, several pharmacological activities including antioxidant, anti-aging, anti-inflammatory, anti-cancerous, anti-diabetic, cardioprotective, and neuroprotective properties, were attributed to RE. However, results from the available human clinical trials were controversial concerning the protective effects of RE against diseases and their sequelae. The reason for these conflicting findings is varied but differences in the characteristics of the enrolled patients, RE doses used, and duration of RE supplementation were proposed, at least in part, as possible causes. In particular, the optimal RE dosage capable of maximizing its health benefits without raising toxicity issues remains an area of extensive research. In this context, while there is a consistent body of literature on the protective effects of RE against diseases, there are relatively few reports investigating its possible toxicity. Indeed, toxicity and adverse effects were reported following consumption of RE; therefore, extensive future studies on the long-term effects, as well as the in vivo adverse effects, of RE supplementation in humans are needed. Furthermore, data on the interactions of RE when combined with other therapies are still lacking, as well as results related to its absorption and bioavailability in the human body. In this review, we collect and summarize the available literature about RE toxicity and side effects. In this process, we analyze in vitro and in vivo studies that have addressed this stilbenoid. These studies suggest that RE still has an unexplored side. Finally, we discuss the new delivery methods that are being employed to overcome the low bioavailability of RE.

Resveratrol prevents Ang II-induced cardiac hypertrophy by inhibition of NF-κB signaling.

BACKGROUND: Pathological cardiac hypertrophy is a hallmark of various cardiovascular diseases (CVD) including chronic heart failure (HF) and an important target for the treatment of these diseases. Aberrant activation of Angiotensin II (Ang II)/AT1R signaling pathway is one of the main triggers of cardiac hypertrophy, which further gives rise to excessive inflammation that is mediated by the key transcription factor NF-κB. Resveratrol (REV) is a natural polyphenol with multiple anti-inflammatory and anti-oxidative effects, however the ability of REV in preventing Ang II-induced cardiac hypertrophy in combination with NF-κB signaling activation remains unclear. METHODS: Murine models of cardiac hypertrophy was conducted via implantation of Ang II osmotic pumps. Primary neonatal rat cardiomyocyte and heart tissues were examined to determine the effect and underlying mechanism of REV in preventing Ang II-induced cardiac hypertrophy. RESULTS: Administrations of REV significantly prevented Ang II-induced cardiac hypertrophy, as well as robustly attenuated Ang II-induced cardiac fibrosis, and cardiac dysfunction. Furthermore, REV not only directly prevented Ang II/AT1R signal transductions, but also prevented Ang II-induced expressions of pro-inflammatory cytokines and activation of NF-κB signaling pathway. CONCLUSIONS: Our study provides important new mechanistic insight into the cardioprotective effects of REV in preventing Ang II-induced cardiac hypertrophy via inhibiting adverse NF-κB signaling activation. Our findings further suggest the therapeutic potential of REV as a promising drug for the treatment of cardiac hypertrophy and heart failure.

Reduction of SIRT1-Mediated Epigenetic Upregulation of Nav1.7 Contributes to Oxaliplatin-Induced Neuropathic Pain.

BACKGROUND: Clinically, neuropathic pain is a severe side effect of oxaliplatin chemotherapy, which usually leads to dose reduction or cessation of treatment. Due to the unawareness of detailed mechanisms of oxaliplatin-induced neuropathic pain, it is difficult to develop an effective therapy and limits its clinical use. OBJECTIVES: The aim of the present study was to identify the role of sirtuin 1 (SIRT1) reduction in epigenetic regulation of the expression of voltage-gated sodium channels 1.7 (Nav1.7) in the dorsal root ganglion (DRG) during oxaliplatin-induced neuropathic pain. STUDY DESIGN: Controlled animal study. SETTING: University laboratory. METHODS: The von Frey test was performed to evaluate pain behavior in rats. Real-time quantitative polymerase chain reaction, western blotting, electrophysiological recording, chromatin immunoprecipitation, and small interfering RNA (siRNA) were used to illustrate the mechanisms. RESULTS: In the present study, we found that both the activity and expression of SIRT1 were significantly decreased in rat DRG following oxaliplatin treatment. The activator of SIRT1, resveratrol, not only increased the activity and expression of SIRT1, but also attenuated the mechanical allodynia following oxaliplatin treatment. In addition, local knockdown of SIRT1 by intrathecal injection of SIRT1 siRNA caused mechanical allodynia in naive rats. Besides, oxaliplatin treatment enhanced the action potential firing frequency of DRG neurons and the expression of Nav1.7 in DRG and activation of SIRT1 by resveratrol reversed this effect. Furthermore, blocking Nav1.7 by ProTx II (a selective Nav1.7 channel blocker) reversed oxaliplatin-induced mechanical allodynia. In addition, histone H3 hyperacetylation at the Nav1.7 promoter in DRG of rats following oxaliplatin treatment was significantly suppressed by activation of SIRT1 with resveratrol. Moreover, both the expression of Nav1.7 and histone H3 acetylation at the Nav1.7 promoter were upregulated in the DRG by local knockdown of SIRT1 with SIRT1 siRNA in naive rats. LIMITATIONS: More underlying mechanism(s) of SIRT1 reduction after oxaliplatin treatment needs to be explored in future research. CONCLUSIONS: These findings suggest that reduction of SIRT1-mediated epigenetic upregulation of Nav1.7 in the DRG contributes to the development of oxaliplatin-induced neuropathic pain in rats. The intrathecal drug delivery treatment of activating SIRT1 might be a novel therapeutic option for oxaliplatin-induced neuropathic pain.

Histopathological, physiological and biochemical assessment of resveratrol nanocapsules efficacy in bleomycin-induced acute and chronic lung injury in rats.

Acute lung injury (ALI) is a life-threatening illness which may progress to chronic pulmonary fibrosis (CPF). Resveratrol (RSV), a natural polyphenol, is known to exert several pharmacological effects on lung injury. However, its physicochemical properties and pharmacokinetic profile limit its clinical applications. In this study, RSV was loaded into lipid nanocapsules (LNCs) aiming to overcome these limitations. RSV-LNCs were prepared by phase inversion method and showed small uniform particle size (∼55 nm, PdI 0.04) with high entrapment efficiency >99%. The efficacy of RSV-LNCs in the prophylaxis against ALI and treatment of CPF was investigated in bleomycin-induced lung injury. For assessment of ALI, rats were administered a single oral dose of RSV (10 mg/kg) either free or as RSV-LNCs 4 h before bleomycin and euthanized 3 days later. For CPF, treatments in the same dose were given daily from days 10-20 after bleomycin and rats were euthanized on day-21. Results showed enhanced beneficial role for RSV-LNCs, compared to RSV, in the prevention of ALI as demonstrated by preservation of pulmonary microscopic and ultrastructural architecture and improvement of pulmonary functions. Analysis of BALF revealed reduction in oxidative stress markers, IL-6 level, leukocytosis and neutrophilia. iNOS and c-caspase 3 immunohistochemical expression and CD68+ cells immunofluorescence were inhibited. However, RSV-LNCs failed to show any improvement in oxidative stress, chronic inflammation, apoptosis and collagen deposition in CPF. In conclusion, RSV-LNCs are promising nanoplatforms for mitigating ALI detrimental effects. Future research investigating higher doses and longer durations of treatment is recommended to evaluate RSV-LNCs anti-fibrotic potential in CPF.

Neuroprotection by Trans-Resveratrol in Rats With Intracerebral Hemorrhage: Insights into the Role of Adenosine A1 Receptors.

Given the neuroprotective effects of trans-resveratrol (RV), this study aimed to investigate the involvement of the adenosine A1 receptor (A1R) in RV-mediated neuroprotection in a rat intracerebral hemorrhage (ICH) model induced by intrastriatal injection of collagenase. Rats were divided into 5 groups: (1) control, (2) sham-operated, (3) ICH pretreated with vehicle, (4) ICH pretreated with RV, and (5) ICH pretreated with RV and the A1R antagonist DPCPX. At 48 hours after ICH, the rats were subjected to neurological testing. Brain tissues were assessed for neuronal density and morphological features using routine and immunohistochemical staining. Expression of tumor necrosis factor-α (TNF-α), caspase-3, and RIPK3 proteins was examined using ELISA. A1R, MAPK P38, Hsp90, TrkB, and BDNF genes were examined using RT-qPCR. RV protected against neurological deficits and neuronal depletion, restored the expression of TNF-α, CASP3, RIPK3, A1R, and Hsp90, and increased BDNF/TrkB. DPCPX abolished the effects of RV on neurological outcomes, neuronal density, CASP3, RIPK3, A1R, Hsp90, and BDNF. These data indicate that the neuroprotection by RV involves A1R and inhibits CASP3-dependent apoptosis and RIPK3-dependent necroptosis in the perihematoma region; this is likely to be mediated by crosstalk between A1R and the BDNF/TrkB pathway.

Modulation of Memory and Neurochemical Changes by Resveratrol and Environmental Enrichment in Rodent Model of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common cause of dementia that affects one patient every seven seconds, with over 35 million people currently affected worldwide. The aim of the study was to investigate the modulation of memory and neurochemical responses by resveratrol and environmental enrichment (EE) in aluminium chloride (AlCl3) model of Alzheimer's disease in mice. Male mice used for the study were divided into nine groups, of seven animals each. Group I (negative control): 0.2 ml normal saline/kg, Group II: 0.2 ml CMC/kg. Group III: resveratrol (200 mg/kg/), Group IV: CMC and kept in EE, Group V: AlCl3 at dose of 50 mg/kg, Group VI: resveratrol at dose of 200 mg/kg and kept in EE, Group VII: AlCl3 (50 mg/kg) + resveratrol (200 mg/kg), Group VIII: AlCl3 (50 mg/kg) and kept in EE, Group IX: AlCl3 (50 mg/kg) + resveratrol (200 mg/kg) and kept in enriched environment. All treatments were oral and lasted for 8 weeks. Assessments of memory was carried out before treatment, and at weeks 4 and 8, after the first treatment. The mice were sacrificed and hippocampal samples collected for neurochemical analysis. The findings of the study suggest that AlCl3 induced contextual fear memory deficit over time (p < 0.05), which was improved by resveratrol. Both Aß and Nrf2 significantly (p < 0.05) increased in AlCl3 + EE + resveratrol group. In conclusion, Individual treatment with either resveratrol or EE improved memory over the combined treatment in AlCl3 model of AD by decreasing Aß protein concentration.

Resveratrol pre-treatment alleviated caerulein-induced acute pancreatitis in high-fat diet-feeding mice via suppressing the NF-κB proinflammatory signaling and improving the gut microbiota.

BACKGROUND: hyperlipidemia acute pancreatitis (HTG-AP) is a major hidden danger affecting human health, however, whether there is a protective effect of resveratrol on HTG-AP is unclear. Therefore our study was aimed to investigate the preventive effect and the underlying mechanism of resveratrol in the HTG-AP mice model. METHODS: This research was divided into two parts. In the first part, mice were adaptively fed with normal chow or HFD for 6 weeks. From the second week, resveratrol-treated mice were in intragastric administration with resveratrol (45 mg/kg/d) for 4 weeks. In the second part, the procedures were the same as the first part. After the last intragastric administration with resveratrol, all mice were intraperitoneal injections of cerulean. RESULTS: We found resveratrol effectively inhibited pancreatic pathological injury in the HFD, AP, and HTG-AP mice. Resveratrol reduced the LPS, IL-6, TNF-α, and MCP-1 expressions in the HFD mice. Resveratrol also reduced TNF-α, MDA, and MCP-1 expressions and increased SOD and T-AOC expressions in the AP and HTG-AP mice. Furthermore, resveratrol suppressed the NF-κB pro-inflammatory signaling pathway in pancreatic tissues in the AP and HTG-AP mice. Moreover, resveratrol improved the gut microbiota in the HFD mice. CONCLUSION: The resveratrol pre-treatment could attenuate pancreas injury, inflammation, and oxidative stress in the HTG-AP mice, via restraining the NF-κB signaling pathway and regulating gut microbiota. Therefore, Our study proved that the resveratrol pre-treatment had a preventive effect on HTG-AP.

Long-term effects of resveratrol on cognition, cerebrovascular function and cardio-metabolic markers in postmenopausal women: A 24-month randomised, double-blind, placebo-controlled, crossover study.

Ageing and menopause contribute to endothelial dysfunction, causing impaired cerebral perfusion, which is in turn associated with accelerated cognitive decline. In a 14-week pilot study, we showed that supplementation with low-dose resveratrol, a phytoestrogen that can enhance endothelial function, improved cerebrovascular and cognitive functions in postmenopausal women. We sought to confirm these benefits in a larger, longer-term trial. A 24-month randomized, placebo-controlled crossover trial was undertaken in 125 postmenopausal women, aged 45-85 years, who took 75 mg trans-resveratrol or placebo twice-daily for 12 months and then crossover to the alternative treatment for another 12 months. We evaluated within individual differences between each treatment period in measures of cognition (primary outcome), cerebrovascular function in the middle cerebral artery (cerebral blood flow velocity: CBFV, cerebrovascular responsiveness: CVR) and cardio-metabolic markers as secondary outcomes. Subgroup analyses examined effects of resveratrol by life stages. Compared to placebo, resveratrol supplementation resulted a significant 33% improvement in overall cognitive performance (Cohen's d = 0.170, P = 0.005). Women ≥65 years of age showed a relative improvement in verbal memory with resveratrol compared to those younger than 65 years. Furthermore, resveratrol improved secondary outcomes including resting mean CBFV (d = 0.275, P = 0.001), CVR to hypercapnia (d = 0.307, P = 0.027), CVR to cognitive stimuli (d = 0.259, P = 0.032), fasting insulin (d = 0.174, P = 0.025) and insulin resistance index (d = 0.102, P = 0.034). Regular supplementation with low-dose resveratrol can enhance cognition, cerebrovascular function and insulin sensitivity in postmenopausal women. This may translate into a slowing of the accelerated cognitive decline due to ageing and menopause, especially in late-life women. Further studies are warranted to observe whether these cognitive benefits of resveratrol can reduce the risk of dementia.

The effects of resveratrol supplementation in patients with type 2 diabetes, metabolic syndrome, and nonalcoholic fatty liver disease: an umbrella review of meta-analyses of randomized controlled trials.

BACKGROUND: Uncertainty remains about the estimates of the effects for resveratrol supplementation, including the certainty of the evidence for each estimate and the magnitude of the observed impact based on the minimal important difference. OBJECTIVE: We aimed to provide an overview of the effects of resveratrol supplementation, in comparison to control groups, for the management of cardiometabolic risk factors in patients with type 2 diabetes (T2D), metabolic syndrome (MetS), and nonalcoholic fatty liver disease (NAFLD). METHODS: PubMed, Scopus, and ISI Web of Science were searched from inception to May 2021. For each meta-analysis, the mean difference and its 95% CI were recalculated using a random-effects model. The certainty of evidence was rated using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. RESULTS: We identified 11 meta-analyses corresponding to 29 outcomes in 1476 individuals with T2D, 17 meta-analyses reporting 26 outcomes in 727 participants with the MetS, and 10 meta-analyses reporting 24 outcomes in 271 patients with NAFLD. Resveratrol supplementation had beneficial effects on some outcomes such as blood pressure, lipid profile, glycemic control, and insulin resistance in T2D, waist circumference in MetS, and body-weight and inflammation markers in NAFLD; however, for almost all outcomes, the magnitude of the effect was trivial, the certainty of evidence was very low to low, or the number of trials was too few. In the case of glycated hemoglobin (HbA1c), there was evidence that resveratrol can exert favorable and clinically important effects in the short term (<12 wk; mean difference: -1.05%, 95% CI: -2.09%, -0.02%; n = 6; GRADE = moderate). CONCLUSIONS: Current evidence does not support supplementation with resveratrol for the management of cardiometabolic risk factors in patients with T2D, MetS, and NAFLD. In the case of HbA1c, subject to the limitations such as short-term follow-up and small sample size, there was a clinically important effect. The protocol of the present systematic review was registered in Open Science Framework (https://osf.io/ake85; registration doi: 10.17605/OSF.IO/AKE85).

Resveratrol (RV): A pharmacological review and call for further research.

Resveratrol (RV) is a well-known polyphenolic compound in various plants, including grape, peanut, and berry fruits, which is quite famous for its association with several health benefits such as anti-obesity, cardioprotective neuroprotective, antitumor, antidiabetic, antioxidants, anti-age effects, and glucose metabolism. Significantly, promising therapeutic properties have been reported in various cancer, neurodegeneration, and atherosclerosis and are regulated by several synergistic pathways that control oxidative stress, cell death, and inflammation. Similarly, RV possesses a strong anti-adipogenic effect by inhibiting fat accumulation processes and activating oxidative and lipolytic pathways, exhibiting their cardioprotective effects by inhibiting platelet aggregation. The RV also shows significant antibacterial effects against various food-borne pathogens (Listeria, Campylobacter, Staphylococcus aureus, and E. coli) by inhibiting an electron transport chain (ETC) and F0F1-ATPase, which decreases the production of cellular energy that leads to the spread of pathogens. After collecting and analyzing scientific literature, it may be concluded that RV is well tolerated and favorably affects cardiovascular, neurological, and diabetic disorders. As such, it is possible that RV can be considered the best nutritional additive and a complementary drug, especially a therapeutic candidate. Therefore, this review would increase knowledge about the blend of RV as well as inspire researchers around the world to consider RV as a pharmaceutical drug to combat future health crises against various inhumane diseases. In the future, this article will be aware of discoveries about the potential of this promising natural compound as the best nutraceuticals and therapeutic drugs in medicine.

A Randomized Study of Nutritional Supplementation in Patients with Unilateral Wet Age-Related Macular Degeneration.

The purpose of this study is evaluate the efficacy and safety of medicinal products containing the original Age-Related Eye Disease group (AREDS) formulation at doses approved in Europe (EU, control group; n = 59) with a product that adds DHA, lutein, zeaxanthin, resveratrol and hydroxytyrosol to the formula (intervention group; n = 50). This was a multicenter, randomized, observer-blinded trial conducted in patients aged 50 years or older diagnosed with unilateral exudative Age related Macular Degeneration AMD. At month 12, the intervention did not have a significant differential effect on visual acuity compared with the control group, with an estimated treatment difference in Early Treatment Diabetic Retinopathy Study (ETDRS) of -1.63 (95% CI -0.83 to 4.09; p = 0.192). The intervention exhibited a significant and, in most cases, relevant effect in terms of a reduction in some inflammatory cytokines and a greater improvement in the fatty acid profile and serum lutein and zeaxantin concentration. In patients with unilateral wet AMD, the addition of lutein, zeaxanthin, resveratrol, hydroxytyrosol and DHA to the AREDS EU recommended doses in the short-term did not have a differential effect on visual acuity compared to a standard AREDS EU formula but, in addition to improving the fatty acid profile and increasing carotenoid serum levels, may provide a beneficial effect in improving the proinflammatory and proangiogenic profile of patients with AMD.

Resveratrol supplementation and acute pancreatitis: A comprehensive review.

Resveratrol, a natural polyphenolic ingredient extracted from herbs, suppresses oxidative stress and inflammation. We performed a comprehensive review to find any evidence about the effects of Resveratrol on acute pancreatitis (AP). Resveratrol has been found to directly impact cytokine generation. As these factors play a crucial role in the pathophysiology of AP, resveratrol might attenuate AP and its complications. Mechanistically, resveratrol exerts its pharmacological effects through anti-inflammatory and antioxidant mechanisms via interaction with different signaling molecules and transcription factors. Indeed, resveratrol might prove to be an effective therapeutic component for AP treatment in the future. In this review, we shed light on potential most recent pathways through which resveratrol might impact the management and control of AP.

Resveratrol loaded glycyrrhizic acid-conjugated human serum albumin nanoparticles for tail vein injection II: pharmacokinetics, tissue distribution and bioavailability.

There are many kinds of biological activities of resveratrol itself, but its clinical application is limited by its poor solubility in water and low bioavailability. Therefore, we have prepared glycyrrhizic acid-conjugated human serum albumin nanoparticles wrapping resveratrol nanoparticles (GL-HSA-RESNPs). The purpose of this study was to investigate the bioavailability, pharmacokinetics and tissue distribution of resveratrol in rats after single-dose tail vein injection administration of GL-HSA-RESNPs. A sensitive and reliable high performance liquid chromatography (HPLC) method was established to verify the content of resveratrol in rat plasma and organs. The Cmax value after GL-HSA-RESNPs administration was significantly higher than that of resveratrol suspension (933 ± 76.64 ng/mL vs. 618 ± 42.54 ng/mL, p < .01). The Tmax value obtained after GL-HSA-RESNPs administration was significantly shorter than that after resveratrol suspension administration (0.17 ± 0.01 h vs. 0.25 ± 0.01 h, p < .001). The bioavailability of GL-HSA-RESNPs was 4.25 times higher than that of the pure resveratrol. The concentration of resveratrol in the main organs of rats treated with the GL-HSA-RESNPs was higher than that in rats treated with the pure resveratrol. Rats treated with GL-HSA-RESNPs had the highest concentration of resveratrol in their liver. It is indicated that GL-HSA-RESNPs is a promising liver-targeted delivery system that improves the in vivo bioavailability of resveratrol.

Transformation of resveratrol under disinfection conditions.

Trans-resveratrol becomes more and more popular all over the world as a powerful antioxidant. Since its positive properties, including antioxidant, anti-inflammatory, anti-tumor are indisputable, nowadays trans-resveratrol is used as a component of various products from nutriceutics to body care formulations, where it is supposed to behave as natural antioxidant and anti-aging compound. It is also added to food packaging materials to increase their stability or/and prevent oxidation. Nevertheless, being released to the environment resveratrol easily forms various transformation products with potentially negative environmental and health effects. The present paper deals with transformation of pure resveratrol and its formulation used as UV-protectors in conditions of aquatic chlorination. Over 80 transformation products were tentatively identified using gas chromatography-high resolution mass spectrometry (GC-HRMS) and ultra pressure liquid chromatography-high resolution mass spectrometry (UPLC-HRMS). Chlorinated phenols and biphenyls are the most relevant among them. Estimation of toxicity of resveratrol products was carried out using luminescent bacteria V. fischeri tests.