stilbenes and proanthocyanidin

We hypothesized that metabolites of dietary flavonoids attenuate impairments in nitric oxide (NO) bioavailability evoked by glucotoxic conditions mimicking Type 1 or 2 diabetes. To test this, human aortic endothelial cells were treated with either vehicle control, quercetin-3-O-glucoronide, piceatannol or 3-(3-hydroxyphenyl)propionoic acid for 24 h. These are metabolites of quercetin, resveratrol and proanthocyanidin, respectively. Next, cells were exposed to control (5 mM) or high (25 mM) glucose conditions for 48 h, followed by insulin treatment (100 nM, 10 min) to stimulate NO production. In control glucose conditions NO production, phosphorylated to total endothelial nitric oxide synthase (p-eNOS

Topics: Antioxidants; Aorta; Biological Availability; Diabetes Mellitus; Diet; Endothelial Cells; Endothelium, Vascular; Flavonoids; Glucose; Humans; Insulin; Nitric Oxide; Nitric Oxide Synthase Type III; Oxidative Stress; Phosphatidylinositol 3-Kinases; Phosphorylation; Plant Extracts; Proanthocyanidins; Proto-Oncogene Proteins c-akt; Quercetin; Resveratrol; Stilbenes

Angiogenesis plays a central role in wound healing. Among many known growth factors, vascular endothelial growth factor (VEGF) is believed to be the most prevalent, efficacious, and long-term signal that is known to stimulate angiogenesis in wounds. The wound site is rich in oxidants, such as hydrogen peroxide, mostly contributed by neutrophils and macrophages. We proposed that oxidants in the wound microenvironment support the repair process. Proanthocyanidins or condensed tannins are a group of biologically active polyphenolic bioflavonoids that are synthesized by many plants. Previously we have reported that a grape seed proanthycyanidin extract containing 5000 ppm resveratrol (GSPE) potently upregulates oxidant and tumor necrosis factor-alpha inducible VEGF expression in human keratinocytes (Free Radic. Biol. Med. 31:38-42, 2001). Our current objective was to follow up on that finding and test whether GSPE influences dermal wound healing in vivo. First, using a VEGF promoter-driven luciferase reporter construct we observed that the potentiating effect of GSPE on inducible VEGF expression is at the transcriptional level. The reporter assay showed that GSPE alone is able to drive VEGF transcription. Next, two dermal excisional wounds were inflicted on the back of mice and the wounds were left to heal by secondary intention. Topical application of GSPE accelerated wound contraction and closure. GSPE treatment was associated with a more well-defined hyperproliferative epithelial region, higher cell density, enhanced deposition of connective tissue, and improved histological architecture. GSPE treatment also increased VEGF and tenascin expression in the wound edge tissue. Tissue glutathione oxidation and 4-hydroxynonenal immunostaining results supported that GSPE application enhanced the oxidizing environment at the wound site. Oxidants are known to promote both VEGF as well as tenascin expression. In summary, our current study provides firm evidence to support that topical application of GSPE represents a feasible and productive approach to support dermal wound healing.

Topics: Animals; Anthocyanins; Cell Line, Transformed; Drug Evaluation, Preclinical; Endothelial Growth Factors; Epithelial Cells; Feasibility Studies; Gene Expression Regulation; Genes, Reporter; Glutathione; Humans; Intercellular Signaling Peptides and Proteins; Keratinocytes; Luciferases; Lymphokines; Male; Mice; Mice, Inbred BALB C; Neovascularization, Physiologic; Oxidants; Oxidation-Reduction; Phytotherapy; Plant Extracts; Proanthocyanidins; Resveratrol; Seeds; Skin; Stilbenes; Tenascin; Transfection; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors; Vitis; Wound Healing; Wounds, Stab

Resveratrol and trans-resveratrol are powerful phytoestrogens, present in the skins of grapes and other plant foods and wine, which demonstrate a broad spectrum of pharmacological and therapeutic health benefits. Phytoestrogens are naturally occurring plant-derived nonsteroidal compounds that are functionally and structurally similar to steroidal estrogens, such as estradiol, produced by the body. Various studies, reviewed herein, have demonstrated the health benefits of phytoestrogens in addressing climacteric syndrome including vasomotor symptoms and postmenopausal health risks, as well as their anticarcinogenic, neuroprotective and cardioprotective activities and prostate health and bone formation promoting properties. Conventional HRT drugs have been demonstrated to cause serious adverse effects including stroke and gallbladder disease, as well as endometrial, uterine and breast cancers. Recent research demonstrates that trans-resveratrol binds to human estrogen receptors and increases estrogenic activity in the body. We investigated the effects of protykin, a standardized extract of trans-resveratrol from Polygonum cuspidatum, on cardioprotective function, the incidence of reperfusion-induced arrhythmias and free radical production in isolated ischemic/reperfused rat hearts. The rats were orally treated with two different daily doses of protykin for 3 weeks. Coronary effluents were measured for oxygen free radical production by electron spin resonance (ESR) spectroscopy in treated and drug-free control groups. In rats treated with 50 and 100 mg/kg of protykin, the incidence of reperfusion-induced ventricular fibrillation was reduced from its control value of 83% to 75% (p < 0.05) and 33% (p < 0.05), respectively. Protykin was seen to possess cardioprotective effects against reperfusion-induced arrhythmias through its ability to reduce or remove the reactive oxygen species in ischemic/reperfused myocardium. Taken together, these data suggest that trans-resveratrol supplementation may be a potential alternative to conventional HRT for cardioprotection and osteoporosis prevention and may confer other potential health benefits in women.

Topics: Animals; Anthocyanins; Anticarcinogenic Agents; Antioxidants; Dose-Response Relationship, Drug; Estrogens, Non-Steroidal; Female; Free Radicals; Heart Diseases; Humans; Isoflavones; Phytoestrogens; Plant Preparations; Proanthocyanidins; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Resveratrol; Stilbenes; Ventricular Fibrillation

Wine polyphenols were examined for their capacity to protect the lipid and protein moieties of porcine low density lipoproteins (LDL) during oxidation. The efficiency of resveratrol (3, 4', 5, trihydroxystilbene) and defined flavonoids was compared to that of a wine extract (WE) containing 0.5 g/g proanthocyanidols. The efficiency of resveratrol for protecting polyunsaturated fatty acids (PUFA) was higher than that of flavonoids in copper-induced oxidation and lower in AAPH (radical initiator)-induced oxidation. The LDL receptor activity was evaluated by flow cytometry using LDL labeled with fluorescein isothiocyanate (FITC) and Chinese hamster ovary cells (CHO-K1). The incubation of CHO-K1 with FITC-LDL oxidized for 16 h reduced the proportion of fluorescent cells from 97% to 4%. At a concentration of 40 microM, resveratrol and flavonoids completely restored the uptake of copper-oxidized LDL and AAPH-oxidized LDL respectively. Total fluorescence could also be obtained with 20 mg/L of WE with both oxidation systems. These data are consistent with previous findings relative to the formation of degradative products from PUFA. They confirm that resveratrol was more effective than flavonoids as a chelator of copper and less effective as a free-radical scavenger. Moreover, they show that WE, which contained monomeric and oligomeric forms of flavonoids and phenolic acids, protected LDL by both mechanisms.

Topics: Amidines; Animals; Anthocyanins; Antioxidants; Binding, Competitive; Catechin; CHO Cells; Cholesterol Esters; Copper; Cricetinae; Endocytosis; Fatty Acids, Unsaturated; Flavonoids; Lipid Peroxidation; Lipoproteins, LDL; Oxidants; Oxidation-Reduction; Phenols; Phospholipids; Polymers; Proanthocyanidins; Receptors, LDL; Resveratrol; Stilbenes; Swine; Wine