stilbenes and 3-5-dimethoxy-4--hydroxystilbene

Topics: Animals; Central Nervous System Diseases; Glioma; Humans; NF-kappa B; Signal Transduction; Stilbenes

Pterostilbene (PTS), a compound most abundantly found in blueberries, is a natural analog of resveratrol. Several plant species, such as peanuts and grapes, produce PTS. While resveratrol has been extensively studied for its antioxidant properties, recent evidence also points out the diverse therapeutic potential of PTS. Several studies have identified the robust pharmacodynamic features of PTS, including better intestinal absorption and elevated hepatic stability than resveratrol. Indeed, due to its higher bioavailability paired with reduced toxicity compared to other stilbenes, PTS has become an attractive drug candidate for the treatment of several disease conditions, including diabetes, cancer, cardiovascular disease, neurodegenerative disorders, and aging. This review article provides an extensive summary of the nutraceutical potential of PTS in various disease conditions while discussing the crucial mechanistic pathways implicated. In particular, we share insights from our studies about the Nrf2-mediated effect of PTS in diabetes and associated complications. Moreover, we elucidate the important sources of PTS and discuss in detail its pharmacokinetics and the range of formulations and routes of administration used across experimental studies and human clinical trials. Furthermore, this review also summarizes the strategies successfully used to improve dietary availability and the bio-accessibility of PTS.

Topics: Antioxidants; Health Promotion; Humans; NF-E2-Related Factor 2; Resveratrol; Stilbenes

Contractile dysfunction and fatal arrhythmias are the hallmarks of myocardial ischemia/reperfusion (I/R) injury. Pterostilbene has notable cardioprotective effects, but its main mechanisms are not fully understood. Here, we investigated the effect of PTE on myocardial hemodynamics, arrhythmias, inflammatory/oxidative responses, and the causal role of the JAK2/STAT3 pathway in rats with acute myocardial I/R injury. Sixty male 7-8 months Sprague-Dawley rats (n=10/each group) experienced in vivo model of myocardial I/R injury through 40-min LAD coronary artery occlusion and subsequent 24-h reperfusion. PTE at concentrations of 5 and 25 mg/kg was intraperitoneally administered to rats five min before reperfusion. Cardiac hemodynamics, reperfusion-induced ventricular arrhythmias, infarct size, inflammatory cytokines, oxidative stress markers, the activity of the JAK2/STAT3 pathway were measured as the endpoints. Administration of PTE to I/R-injured rats recovered myocardial contractile function and reduced infarct size and ventricular arrhythmias counts and incidence in a dose-dependent manner. PTE at 25 mg/kg significantly and more potently reduced the levels of inflammatory mediators NF-?B, TNF-?, and IL-1?, suppressed intracellular ROS production, augmented the activity of glutathione, and manganese-superoxide dismutase, and upregulated the JAK2 and STAT3 phosphorylation. Importantly, pretreatment of rats with Ag490 as a JAK2 inhibitor significantly abolished the cardioprotective and signaling effects of PTE in I/R rats. PTE exerts significant protective effects on reducing arrhythmias and myocardial infarction and enhancing cardiac function by stimulating JAK2/STAT3-related suppression of inflammatory and oxidative reactions in the I/R injury setting.

Topics: Animals; Apoptosis; Cytokines; Glutathione; Inflammation Mediators; Interleukin-1; Janus Kinase 2; Male; Manganese; Myocardial Infarction; Myocardial Reperfusion Injury; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Reperfusion Injury; Stilbenes; Superoxide Dismutase

This study investigated the influence of carrier oils on the

Topics: Animals; Biological Availability; Caco-2 Cells; Catechin; Corn Oil; Delayed-Action Preparations; Emulsions; Excipients; Gonads; Humans; Mice; Micelles; Oils; Pectinidae; Proteins; Stilbenes

Pterostilbene is a trans stilbene compound, which is an effective component of herbaceous plants such as Dalbergia woods and Vaccinium. Although pterostilbene has many uses in anti-inflammatory, anti-oxidant and anti-tumor, its whitening effect is drawing more and more attention, the mechanism of melanogenesis and melanosome transport still needs further study. In this research, we tried to further investigate how melanocyte melanogenesis is affected by pterostilbene and whether pterostilbene play a part in melanin transport. Our results showed that pterostilbene has a potent inhibitory effect on melanogenesis in B16F10 cells (3 μM, p < 0.001), in-vitro human skin (10 μM, p < 0.05) and zebrafish embryos (3 μM, p < 0.01). Besides, pterostilbene not only inhibited melanogenesis, but also inhibited melanocyte dendritic development and melanosome transport. Pterostilbene mainly plays a role by inhibiting cAMP/PKA/CREB signal pathway. After the cAMP/PKA/CREB signaling pathway was inhibited, tyrosinase activity and the expression of MITF, TYR, Rab27A, Rab17 and gp100 were decreased, which in turn suppressed melanogenesis, melanocyte dendritic development and melanosome transport. Our findings showed that pterostilbene can potently inhibit melanogenesis and melanosome transport, suggesting the applicability of pterostilbene in skin lightning. Therefore, a novel pharmacologic way to treat hyperpigmentation has been proposed.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Cell Line, Tumor; Humans; Melanins; Melanocytes; Melanosomes; Microphthalmia-Associated Transcription Factor; Monophenol Monooxygenase; Stilbenes; Zebrafish

A novel pro-phytomicelle formulation with small molecule phytochemicals as nanomaterials was developed for the oral delivery of pterostilbene (PTE) in our previous work. The present report was designed to preclinically evaluate the

Topics: Acetaminophen; Animals; Chemical and Drug Induced Liver Injury, Chronic; Cytokines; HMGB1 Protein; Liver; Mice; Rats; Stilbenes; Treatment Outcome

Pterostilbene is a stilbene flavonoid that occurs naturally in various plants as well as produced by genetic engineering. It exhibits anti-inflammatory, analgesic, anti-oxidant and neuroprotective activities. This research was aimed to determine the potential of pterostilbene against arthritis and peripheral neuropathy in Complete Freund's Adjuvant (CFA) induced arthritis. Rat hind paw was injected with 0.1 ml CFA to induce arthritis. Standard control animals received oral methotrexate (3 mg/kg/week). Pterostilbene at 12.5, 25 and 50 mg/kg was given orally to different groups of arthritic rats from day 7-28 for 21 days. Pterostilbene significantly reduced paw diameter and retarded the decrease in body weight of arthritic rats. It profoundly (p < 0.05-0.0001) reduced lipid peroxidation and nitrites, while increased superoxide dismutase (SOD) in the liver tissue. Pterostilbene treatment significantly (p < 0.0001) reduced TNF-α and IL-6 levels. Pterostilbene markedly improved (p < 0.05-0.001) motor activity and showed analgesic effect in arthritic rats at 25 and 50 mg/kg as compared to disease control rats. Furthermore, it notably (p < 0.05-0.0001) increased SOD activity, nitrites, noradrenaline and serotonin levels in the sciatic nerve of arthritic rats. Treatment with pterostilbene also ameliorated the CFA-induced pannus formation, cartilage damage and synovial hyperplasia in the arthritic rat paws. It is determined from the current study that pterostilbene was effective in reducing CFA-induced arthritis in rats through amelioration of oxidative stress and inflammatory mediators. It was also effective to treat peripheral neuropathy through modulation of oxidative stress and neurotransmitters in sciatic nerves.

Topics: Analgesics; Animals; Arthritis, Experimental; Cytokines; Freund's Adjuvant; Neurotransmitter Agents; Nitrites; Oxidative Stress; Peripheral Nervous System Diseases; Rats; Rats, Wistar; Stilbenes; Superoxide Dismutase

Diabetes incidence is rising globally at an accelerating rate causing issues at both the individual and societal levels. However, partly inspired by Ayurvedic medicine, a naturally occurring compound called pterostilbene has been demonstrated to protect against diabetes symptoms, though mainly in rats. The purpose of this study was to investigate the putative protective effect of pterostilbene on the two main aspects of diabetes, namely insulin resistance and decreased insulin secretion, in mice. To accomplish this, we employed diet-induced obese as well as streptozotocin-induced diabetic C57BL/6NTac mice for fasting glucose homeostasis assessment, tolerance tests and pancreas perfusions. In addition, we used the polygenic model of diabetes TALLYHO/JngJ to assess for prevention of β-cell burnout. We found that the diet-induced obese C57BL/6NTac mice were insulin resistant, but that pterostilbene had no impact on this or on overall glucose regulation. We further found that the reported protective effect of pterostilbene against streptozotocin-induced diabetes was absent in C57BL/6NTac mice, despite a promising pilot experiment. Lastly, we observed that pterostilbene does not prevent or delay onset of β-cell burnout in TALLYHO/JngJ mice. In conjunction with the literature, our findings suggest variations in the response to pterostilbene between species or between strains of species.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Experimental; Disease Models, Animal; Glucose; Insulin; Insulin Secretion; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Rats; Stilbenes; Streptozocin

This study was focused to determine an individual and combined effect of mycotoxin citrinin (CIT) and two compounds of the stilbene family- resveratrol (RES) and his dimethyl ether analogue pterostilbene (PTE) which have many health benefits. As a model the human adenocarcinoma cell line HT-29 was used which may exhibits the properties of small intestine cells. Viability, plasma membrane integrity, lysosomal functionality, intracellular production of superoxide anions and superoxide dismutase activity were examined. The results indicate that concentrations of 50 and 100 μg/mL of the tested compounds were cytotoxic in mostly monitored parameters and probably caused apoptosis. HT-29 cells were more sensitive to PTE than to RES with a higher antioxidant effect of PTE than RES, which may be caused by its chemical structure. Both stilbenes at medium doses act as effective superoxide anions scavengers leading to reduction of oxidative stress and consequent cell damage. The nontoxic concentration of RES (25 µg/mL) protects the HT-29 cell line faced to the toxicity of CIT at 25 µg/mL by increasing viability of cells and by reducing the superoxide production induced by CIT concentrations of 12.5 µg/mL and 25 µg/mL.

Topics: Antioxidants; Apoptosis; Cell Membrane; Cell Survival; Citrinin; Dose-Response Relationship, Drug; Drug Interactions; HT29 Cells; Humans; Oxidative Stress; Resveratrol; Stilbenes

Resveratrol, a natural compound found in many dietary plants and in red wine, plays an important role in the prevention of many human pathological processes, including inflammation, atherosclerosis and carcinogenesis. We have shown that the antiproliferative activity of resveratrol correlated with its ability to inhibit the replicative pols (DNA polymerases) alpha and delta in vitro [Stivala, Savio, Carafoli, Perucca, Bianchi, Maga, Forti, Pagnoni, Albini, Prosperi and Vannini (2001) J. Biol. Chem. 276, 22586-22594]. In this paper, we present the first detailed biochemical investigation on the mechanism of action of resveratrol towards mammalian pols. Our results suggest that specific structural determinants of the resveratrol molecule are responsible for selective inhibition of different mammalian pols, such as the family B pol alpha and the family X pol lambda. Moreover, the resveratrol derivative trans-3,5-dimethoxy-4-hydroxystilbene, which is endowed with a strong antiproliferative activity (Stivala et al., 2001), can inhibit pols alpha and lambda and also suppress the in vitro SV40 DNA replication. The potency of inhibition is similar to that of aphidicolin, an inhibitor of the three replicative pols alpha, delta and epsilon. Our findings establish the necessary background for the synthesis of resveratrol derivatives having more selective and potent antiproliferative activity.

Topics: Amino Acid Sequence; Animals; Binding Sites; DNA Nucleotidyltransferases; DNA Replication; DNA-Directed DNA Polymerase; Humans; Kinetics; Mammals; Molecular Structure; Nucleic Acid Synthesis Inhibitors; Protein Binding; Resveratrol; Stilbenes; Structure-Activity Relationship; Substrate Specificity