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Extensive research within the last decade has revealed that most chronic illnesses such as cancer, cardiovascular and pulmonary diseases, neurological diseases, diabetes, and autoimmune diseases exhibit dysregulation of multiple cell signaling pathways that have been linked to inflammation. Thus mono-targeted therapies developed for the last two de...
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Context 1
... word resveratrol is derived from a Latin word 'Res' means, "which comes from," from the plant 'veratrum' and 'ol' indicating the presence of alcohol moiety in the structure. The precursor of resveratrol is phenylalanine and the enzyme stilbene synthase cata- lyzes the reaction. The presence of resveratrol in more than 70 plant species spanning 32 genera has been reported (see Fig. 1). Resveratrol exists in both cis and trans forms and trans is the more stable form. The compound was first isolated from the roots of white hellebore (Veratrum grandifolorum O.Loes) in 1940 (Takaoka) and from the roots of a traditional Japanese and Chinese plant Polygonum cuspi- datum in 1963 by Nonomura et al. 4 The presence of resveratrol and its natural analogs piceatannol and pterostilbene were reported from peanuts (Arachis spp), different types of berries (Vaccinium sp) etc. Fresh grape skin contains about 50-100 mg of resveratrol per gram wet weight thereby contributing relatively high concentration of resveratrol in red wine and grape juice. A series of epidemiological studies have proven an inverse relationship between consumption of red wine and incidence of cardiovascular diseases and phenomenon is termed the "French Paradox." Several studies have shown that the cardiovascular effect of red wine is mainly due to its resveratrol content. Some of the other major sources are given in Figure 1 and a detailed description of major plant sources of resveratrol are described elsewhere. 5,6 Structure and Chemistry of Resveratrol Resveratrol's stilbene-based structure has two phenolics rings linked by a styrene double bond, which allows cis and trans orienta- tion to generate 3,4',5-trihydroxystilbene. The cis and trans forms can be separated by high performance liquid chromatography (HPLC) based on their absorption maxima. The cis form has a λmax of 288 nm and that of the trans is 308 nm. On exposure to UV, the trans form is changed into the cis form, so the isolation is generally performed in dark conditions. 7 Several studies conducted under various conditions showed that trans-resveratrol remained stable for several months (except in high pH buffers) when completely protected from light. Now there are methods to assay both the isomers. 8 Resveratrol is a white powder with a slight yellow cast. It is highly soluble in ethanol and dimethylsulfoxide (DMSO) and sparingly soluble in water. The photometric and flourimetric analysis of trans-resveratrol was performed by several investigators. The photometric study was carried out in an aqueous medium, and it was observed that there was no spectral changes for the absorption band at 310 nm for pH values less than 6.5; however, a bathochromic shift was observed in basic medium, with a new maximum appearing centered at 343 nm for pH values higher than 10.0. The pK a value of this polyphenol is highly influenced by the alcoholic percentage in the working medium. ...
Context 2
... word resveratrol is derived from a Latin word 'Res' means, "which comes from," from the plant 'veratrum' and 'ol' indicating the presence of alcohol moiety in the structure. The precursor of resveratrol is phenylalanine and the enzyme stilbene synthase cata- lyzes the reaction. The presence of resveratrol in more than 70 plant species spanning 32 genera has been reported (see Fig. 1). Resveratrol exists in both cis and trans forms and trans is the more stable form. The compound was first isolated from the roots of white hellebore (Veratrum grandifolorum O.Loes) in 1940 (Takaoka) and from the roots of a traditional Japanese and Chinese plant Polygonum cuspi- datum in 1963 by Nonomura et al. 4 The presence of resveratrol and its natural analogs piceatannol and pterostilbene were reported from peanuts (Arachis spp), different types of berries (Vaccinium sp) etc. Fresh grape skin contains about 50-100 mg of resveratrol per gram wet weight thereby contributing relatively high concentration of resveratrol in red wine and grape juice. A series of epidemiological studies have proven an inverse relationship between consumption of red wine and incidence of cardiovascular diseases and phenomenon is termed the "French Paradox." Several studies have shown that the cardiovascular effect of red wine is mainly due to its resveratrol content. Some of the other major sources are given in Figure 1 and a detailed description of major plant sources of resveratrol are described elsewhere. 5,6 Structure and Chemistry of Resveratrol Resveratrol's stilbene-based structure has two phenolics rings linked by a styrene double bond, which allows cis and trans orienta- tion to generate 3,4',5-trihydroxystilbene. The cis and trans forms can be separated by high performance liquid chromatography (HPLC) based on their absorption maxima. The cis form has a λmax of 288 nm and that of the trans is 308 nm. On exposure to UV, the trans form is changed into the cis form, so the isolation is generally performed in dark conditions. 7 Several studies conducted under various conditions showed that trans-resveratrol remained stable for several months (except in high pH buffers) when completely protected from light. Now there are methods to assay both the isomers. 8 Resveratrol is a white powder with a slight yellow cast. It is highly soluble in ethanol and dimethylsulfoxide (DMSO) and sparingly soluble in water. The photometric and flourimetric analysis of trans-resveratrol was performed by several investigators. The photometric study was carried out in an aqueous medium, and it was observed that there was no spectral changes for the absorption band at 310 nm for pH values less than 6.5; however, a bathochromic shift was observed in basic medium, with a new maximum appearing centered at 343 nm for pH values higher than 10.0. The pK a value of this polyphenol is highly influenced by the alcoholic percentage in the working medium. ...
Citations
... RSV (3, 5, 4′-trihydroxystilbene) is a phenolic micronutrient agent, which is produced naturally by about 70 various types of plant species (including grapes, berries, chocolate, peanuts, and pines). RSV was initially defined as an antibiotic formed against environmental stresses, such as infection, radiation, and pathogenic conditions (36). Studies conducted in animal models reported that the only side effect of RSV consumption was the onset of diarrhea after receiving 200 mg of RSV daily, which was not associated with clinical complications. ...
Background
Diabetes mellitus (DM) is a category of metabolic conditions affecting about 5% of people worldwide. High mortality associated with DM is mostly due to its severe clinical complications, including diabetic nephropathy, retinopathy, neuropathy, and cardiomyopathy. Resveratrol (RSV) is a natural, biologically active polyphenol known to have various health-promoting effects in animal models and humans.
Objective
In this review, we have reviewed the preventive and therapeutic role of RSV on diabetes complications with emphasis on its molecular mechanisms of action.
Methods
To prepare this review, all the basic and clinical available literatures regarding this topic were gathered through electronic databases, including PubMed, Web of Science, Scopus, and Google Scholar. Therefore, we summarized previous studies that have evaluated the effects of RSV on diabetic complications and their mechanisms. Only English language studies published up to January 2023 were included in this review.
Results
RSV improves glucose homeostasis, decreases insulin resistance, induces autophagy, regulates lipid metabolism, protects pancreatic β-cells, ameliorates metabolic disorders, and increases the GLUT4 expression. These effects induced by RSV are strongly associated with ability of this polyphenol agent to elevation expression/activity of AMP-activated protein kinase and Sirtuin 1 in various organs of diabetic subjects, which leads to prevention and therapy of diabetic complications. In addition, antioxidant and anti-inflammatory properties of RSV were reported to be involved in its action in diabetic complications, such as retinopathy and nephropathy.
Conclusion
RSV is a promising compound for improving diabetic complications. However, the exact antidiabetic mechanisms of RSV need to be further investigated.
... Resveratrol (3,4′,5-trihydroxystilbene), a phytoalexin, occurs naturally in a number of dietary sources, including grapes and their products, such as red wines, and other plants, such as berries, plums, and peanuts [20]. Resveratrol has attracted significant attention in the scientific community due to the pharmacological activities that have been reported. ...
Oxygen therapy provides an important treatment for preterm and low-birth-weight neonates, however, it has been shown that prolonged exposure to high levels of oxygen (hyperoxia) is one of the factors contributing to the development of bronchopulmonary dysplasia (BPD) by inducing lung injury and airway hyperreactivity. There is no effective therapy against the adverse effects of hyperoxia. Therefore, this study was undertaken to test the hypothesis that natural phytoalexin resveratrol will overcome hyperoxia-induced airway hyperreactivity, oxidative stress, and lung inflammation. Newborn rats were exposed to hyperoxia (fraction of inspired oxygen - FiO2>95 % O2) or ambient air (AA) for seven days. Resveratrol was supplemented either in vivo (30 mg·kg-1·day-1) by intraperitoneal administration or in vitro to the tracheal preparations in an organ bath (100 μM). Contractile and relaxant responses were studied in tracheal smooth muscle (TSM) using the in vitro organ bath system. To explain the involvement of nitric oxide in the mechanisms of the protective effect of resveratrol against hyperoxia, a nitric oxide synthase inhibitor – Nω-nitro-L-arginine methyl ester (L-NAME), was administered in some sets of experiments. The superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities and the tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) levels in the lungs were determined. Resveratrol significantly reduced contraction and restored the impaired relaxation of hyperoxia-exposed TSM (p<0.001). L-NAME reduced the inhibitory effect of resveratrol on TSM contractility, as well as its promotion relaxant effect (p<0.01). Resveratrol preserved the SOD and GPx activities and decreased the expression of TNF-α and IL-1β in hyperoxic animals. The findings of this study demonstrate the protective effect of resveratrol against hyperoxia-induced airway hyperreactivity and lung damage and suggest that resveratrol might serve as a therapy to prevent the adverse effects of neonatal hyperoxia. Keywords: Bronchopulmonary dysplasia • Hyperoxia • Airway hyperreactivity • Resveratrol • Pro-inflammatory cytokines
... Furthermore, the study has shown that curcumin promotes the regeneration effect in LDH mice [22]. Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a compound which is found in different herbal materials, especially grape skin [26,62]. It has represented pharmacological properties, including antioxidant, anti-tumorigenic, immunomodulatory, anti-inflammatory, and cardiovascular protective effects [26,[62][63][64][65]. ...
... Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is a compound which is found in different herbal materials, especially grape skin [26,62]. It has represented pharmacological properties, including antioxidant, anti-tumorigenic, immunomodulatory, anti-inflammatory, and cardiovascular protective effects [26,[62][63][64][65]. The anti-inflammatory and analgesic effects of resveratrol were shown by inhibiting the expression of TNF-α, IL-1, and mechanical hypersensitivity in rats with radiculopathy caused by NP. ...
Sciatica commonly refers to radicular leg pain which is mainly caused by lumbar disc herniation (LDH) and affects the daily functional ability of many patients in the world. However, according to the side effects and short-term benefits of its treatments, new therapeutic agents such as natural products are needed. The aim of this study was to comprehensively review the effectiveness of plant-derived products for the treatment of sciatica. Electronic databases, including Medline (via PubMed), Scopus, and Web of Science, were searched from inception to 17 August 2023 for this comprehensive review. English language papers reporting preclinical and clinical evaluations of the effectiveness of herbal products, including medicinal plants, multi-component herbal preparations, and phytochemicals on sciatica, radicular pain, or LDH, were included. Studies on neuropathic pain due to reasons other than sciatica, radicular pain, or LDH were excluded. From a total of 5666 papers identified in the primary search, 16 (including 4 clinical and 12 preclinical studies) were finally included. Most of the plant-derived treatments mentioned in this review belonged to the polyphenol family or contained high concentrations of various polyphenols. From the results obtained, polyphenols relieved sciatica by reducing inflammation and oxidative stress, mainly through the inhibition of mitogen-activated protein kinases pathways. In conclusion, plant-derived medicines have the potential to improve the quality of life and functional ability of sciatica patients by relieving symptoms. However, further preclinical and clinical studies are suggested to prove the safety and efficacy of such herbal medicines for sciatica.
... Resveratrol (3,5,4'-trihydroxystilbene) is a polyphenol with an antioxidant function found in numerous plant species and red wine (Harikumar and Aggarwal, 2008). Resveratrol has been applied in several studies in mammalian reproduction (Pasquariello et al., 2020). ...
Cryoprotectants are required to reduce damage caused to the cells due to low temperatures during the cryopreservation. Antifreeze proteins (AFP) have a well-known role in cell membrane protection, while resveratrol is a potent antioxidant. This study assessed the effect of the association of resveratrol concentrations and AFP I in a ram semen extender. Pooled semen of four rams was allocated into six treatments in a factorial arrangement: (CONT, only the semen extender); only AFP I (ANT: 0.1 µg/mL of AFP I), only resveratrol, one treatment with two levels (10 µM/mL or 50 µM/mL of resveratrol); and two treatments with the interactions, with one AFP I and one of the two levels of resveratrol (0.1 µg/mL of AFP I with 10 µM/mL resveratrol; 0.1 µg/mL of AFP I with 50 µM/mL resveratrol). No interaction between factors was observed on sperm kinetics, plasma membrane integrity, hypo-osmotic test, and mitochondrial activity parameters. There was a high probability (P = 0.06) of reducing sperm cells with functional membrane percentage in the hypo-osmotic test and increasing the percentage of sperm with high mitochondrial activity (P = 0.07) was observed in AFP presence. An interaction of AFP and resveratrol was observed in non-capacitated sperm (P = 0.009), acrosomal reaction (P = 0.034), and sperm binding (P = 0.04). In conclusion, the association of resveratrol and AFP did not improve the quality of frozen-thawed semen and even promoted deleterious effects compared to their single addition in the semen extender. The supplementation of 50 µM/mL of resveratrol improved the outcomes of frozen-thawed ram sperm, being a potential cryoprotectant.
... Its active trans form (trans-3,5,4'-trihydroxystilbene) has multiple health benefits shown in years of preclinical research. It is a powerful antioxidant that also exhibits anti-inflammatory, anti-aging and anti-neurodegenerative properties [1][2][3][4], among others. Animal studies showed that transresveratrol is able to cross the blood-brain barrier [5]. ...
Resveratrol is a natural phenolic compound with known benefits against neurodegeneration. We analyzed in vitro the protective mechanisms of resveratrol against the proinflammatory monomeric C-reactive protein (mCRP). mCRP increases the risk of AD after stroke and we previously demonstrated that intracerebral mCRP induces AD-like dementia in mice. Here, we used BV2 microglia treated with mCRP for 24 h in the presence or absence of resveratrol. Cells and conditioned media were collected for analysis. Lipopolysaccharide (LPS) has also been implicated in AD progression and so LPS was used as a resveratrol-sensitive reference agent. mCRP at the concentration of 50 µg/mL activated the nitric oxide pathway and the NLRP3 inflammasome pathway. Furthermore, mCRP induced cyclooxygenase-2 and the release of proinflammatory cytokines. Resveratrol effectively inhibited these changes and increased the expression of the antioxidant enzyme genes Cat and Sod2. As central mechanisms of defense, resveratrol activated the hub genes Sirt1 and Nfe2l2 and inhibited the nuclear translocation of the signal transducer NF-ĸB. Proinflammatory changes induced by mCRP in primary mixed glial cultures were also protected by resveratrol. This work provides a mechanistic insight into the protective benefits of resveratrol in preventing the risk of AD induced by proinflammatory agents.
... Resveratrol is a non-flavonoid polyphenol compound found in fruits such as blueberries and many red grape varieties (22,23). Resveratrol plays an important role in various biological functions, exerting anti-inflammatory, antioxidant, anticancer, and antineurodegenerative effects (24)(25)(26). A previous study found that resveratrol mainly had anti-inflammatory effects on macrophages (27). ...
Introduction
Resveratrol is an immune modulator that can reduce M1 macrophage polarization in vitro . Reducing macrophage recruitment and M1 polarization can prevent corneal allograft rejection (CGR). In this study, rat corneal allograft rejection models were established to explore the effects of resveratrol on CGR and macrophages and the underlying mechanisms after corneal transplantation.
Methods
Corneal allograft models were established, and 100 mg/kg resveratrol was injected intraperitoneally. The corneal allografts were assessed clinically using the Holland rejection scoring system, anterior segment photography, and anterior segment optical coherence tomography. Corneal macrophages, pro-inflammatory cytokines, and corneal lymphatic vessels were detected using hematoxylin and eosin staining, immunofluorescence staining, and real-time quantitative polymerase chain reaction (qRT-PCR). Dendritic cells (DCs) in cervical lymph nodes were explored using flow cytometry. RNA sequencing experiments were conducted to identify the mechanisms through which resveratrol affected CGR. The results were verified using Simple Western analysis. Pro-inflammatory cytokines by macrophages in vitro were measured using qRT-PCR and enzyme-linked immunosorbent assays.
Results
Resveratrol significantly prolonged the survival of corneal grafts and reduced graft edema and central corneal thickness. Corneal macrophage recruitment and M1 macrophage polarization decreased significantly after corneal transplantation in the resveratrol group. Resveratrol also reduced pro-inflammatory cytokines in corneal grafts and suppressed the early generation of cornea lymphatic vessels and the recruitment of cornea inflammatory cells 14 days after surgery. Resveratrol decreased the proportion of DCs in ipsilateral cervical lymph nodes. The effect of resveratrol on CGR was related to the phosphatidylinositol 3-kinase/protein kinase-B (PI3K/Akt) pathway. Resveratrol reduced the secretion of pro-inflammatory cytokines by M1 macrophages in vitro .
Conclusion
Our findings suggest that resveratrol can reduce corneal macrophage recruitment and M1 macrophage polarization after corneal transplantation in rats and prevent CGR. The PI3K/Akt pathway may be an important mechanism that warrants further research.
... Antioxidant, anticancer, anti-inflammatory, immunomodulatory, hypotensive, and hypolipidemic qualities are only some of the many biological effects demonstrated by resveratrol. Obesity, cardiovascular disease, cancer, and neurological diseases are just some of the conditions it has been proven to help with (Harikumar andAggarwal, 2008, Meng et al., 2020). As a result of its ability to reduce oxidative stress, reduce inflammation, boost mitochondrial function, and control apoptosis, it has been the subject of numerous studies demonstrating its value in treating ageing (Wang et al., 2019, Ginés et al., 2017. ...
Abstract
Because aging leads to multiple health problems associated with changes in the structure and functions of a different organ
system, this study aimed to assess the effect of aging on the histology of renal tissue in rats of various ages and the possible
protective role of resveratrol. In the present study, twenty-four male Wistar albino rats were separated into three groups of eight
animals each, including rats adult aged (6 months), and old-aged (24 months old). The elderly resveratrol-treated group was
administered 25 mg/kg/day of resveratrol diluted in distilled water orally via gastric tube. The treatment lasted three months. At
the end of the experiment, blood was drawn for serum creatinine analysis, the animals were sacrificed, and the kidneys were
removed and processed for histological investigation. The findings revealed variable changes in kidney tissue, including glomer-
ulosclerosis, compensatory glomerular hypertrophy, tubulointerstitial fibrosis, thickened glomerular basement membrane, arteri-
al sclerosis, tubular dilatation with cast formation, atrophy of the tubules, infiltration of inflammatory cells, a rise in the rate of
apoptotic cells, and a decrease in the glomerular number. These histological changes were associated with increased serum
creatinine levels and kidney malondialdehyde (MDA), a marker of lipid peroxidation. The use of RES (Resveratrol) improved the
creatinine level with a decrease in the MDA and improved the histological changes of aged kidney. As a result, the progression
of aging was accompanied by different histological variations that interfered with the physiological functioning of the kidney,
predisposing older persons to renal illnesses. Utilizing RES as a prophylactic and/or therapeutic medicine for aging-related re
... However, further evidence is needed to confirm its effectiveness [30][31][32][33][34][35]. At the molecular level, RSV displays antioxidant and anti-inflammatory action in numerous organs and tissues, including the cardiovascular system [28,[36][37][38]. Furthermore, this polyphenol inhibits PKCα and stimulates the production of nitric oxide through the activation of eNOS, which enhances the integrity of the endothelium [39,40]. ...
PREP1 is a homeodomain transcription factor that impairs metabolism and is involved in age-related aortic thickening. In this study, we evaluated the role of PREP1 on endothelial function. Mouse Aortic Endothelial Cells (MAECs) transiently transfected with a Prep1 cDNA showed a 1.5- and 1.6-fold increase in eNOSThr495 and PKCα phosphorylation, respectively. Proinflammatory cytokines Tnf-α and Il-6 increased by 3.5 and 2.3-fold, respectively, in the presence of Prep1, while the antioxidant genes Sod2 and Atf4 were significantly reduced. Bisindolylmaleimide reverted the effects induced by PREP1, suggesting PKCα to be a mediator of PREP1 action. Interestingly, resveratrol, a phenolic micronutrient compound, reduced the PREP1 levels, eNOSThr495, PKCα phosphorylation, and proinflammatory cytokines and increased Sod2 and Atf4 mRNA levels. The experiments performed on the aorta of 18-month-old Prep1 hypomorphic heterozygous mice (Prep1i/+) expressing low levels of this protein showed a 54 and 60% decrease in PKCα and eNOSThr495 phosphorylation and a 45% reduction in Tnf-α levels, with no change in Il-6, compared to same-age WT mice. However, a significant decrease in Sod2 and Atf4 was observed in Prep1i/+ old mice, indicating the lack of age-induced antioxidant response. These results suggest that Prep1 deficiency partially improved the endothelial function in aged mice and suggested PREP1 as a novel target of resveratrol.
... Polyphenols diminish RPE death, opacification of the lens, and BRB breakdown [231]. Resveratrol, an antioxidant and polyphenol phytoalexin rich in many plant products and fruits [232], prevents excessive VEGF production and secretion in ARPE-19 cells subjected to oxidative stress [233] and in human retinal pigment epithelial cultures [234], and it protects against blue-light-induced ARPE-19 cell death [235] and laser-induced CNV [236,237]. In a mouse model of CNV, a strong correlation of omega-3 long-chain-polyunsaturated fatty acid in decreasing CNV lesions has been found [238], in part acting through adiponectin [227] and cytochrome P450 enzyme metabolites [239,240]. ...
Oxidative stress plays a crucial role in aging-related eye diseases, including age-related macular degeneration (AMD), cataracts, and glaucoma. With age, antioxidant reparative capacity decreases, and excess levels of reactive oxygen species produce oxidative damage in many ocular cell types underling age-related pathologies. In AMD, loss of central vision in the elderly is caused primarily by retinal pigment epithelium (RPE) dysfunction and degeneration and/or choroidal neovascularization that trigger malfunction and loss of photo-sensing photoreceptor cells. Along with various genetic and environmental factors that contribute to AMD, aging and age-related oxidative damage have critical involvement in AMD pathogenesis. To this end, dietary intake of antioxidants is a proven way to scavenge free radicals and to prevent or slow AMD progression. This review focuses on AMD and highlights the pathogenic role of oxidative stress in AMD from both clinical and experimental studies. The beneficial roles of antioxidants and dietary micronutrients in AMD are also summarized.
... Res is a naturally occurring phytoalexin inherent to over 70 plant species, including grapes, legumes, and berries. Res has been shown to suppress or decelerate the development of several chronic disorders, such as cancer and agerelated diseases, including diabetes and cardiovascular diseases [20][21][22]. Its efficacy is mediated by regulating the cell cycle and several pathways associated with cell proliferation, cell death, senescence, and inflammation [22][23][24]. ...
Resveratrol (Res), a polyphenol found in red wine, has been shown to decelerate aging, the progressive loss of physiological integrity and cellular senescence, characterized by the inability to progress through the cell cycle. No successful clinical trials have yet to be completed in humans on dose limitations. Yet, the potent anti-aging and anti-senescence efficacy of Res has been documented in several in vivo animal models. In this review, we highlight the molecular mechanisms of Res efficacy in anti-aging disorders, such as diabetes, neurodegenerative disorders, eye diseases, and cardiovascular diseases.
