stilbenes and Erectile-Dysfunction

Functional foods describe the importance of foods in promoting health and preventing diseases aside their primary role of providing the body with the required amount of essential nutrients such as proteins, carbohydrates, vitamins, fats, and oils needed for its healthy survival. This review explains the interaction of functional food bioactive compounds including polyphenols (phenolic acids [hydroxybenzoic acids and hydroxycinnamic acids], flavonoids [flavonols, flavones, flavanols, flavanones, isoflavones, proanthocyanidins], stilbenes, and lignans), terpenoids, carotenoids, alkaloids, omega-3 and polyunsaturated fatty acids, among others with critical enzymes (α- amylase, α- glucosidase, angiotensin-I converting enzyme [ACE], acetylcholinesterase [AChE], and arginase) linked to some degenerative diseases (type-2 diabetes, cardiovascular diseases [hypertension], neurodegenerative diseases [Alzheimer's disease] and erectile dysfunction). Different functional food bioactive compounds may synergistically/additively confer an overwhelming protection against these degenerative diseases by modulating/altering the activities of these critical enzymes of physiological importance.

Topics: Alkaloids; Cardiovascular Diseases; Carotenoids; Chronic Disease; Diabetes Mellitus, Type 2; Dietary Supplements; Erectile Dysfunction; Flavonoids; Functional Food; Health Promotion; Humans; Lignans; Male; Neurodegenerative Diseases; Nutritional Requirements; Phenols; Polyphenols; Stilbenes

The aim of this study was to investigate the effect of resveratrol (RVT) on sildenafil-induced relaxations of isolated corpus cavernosum in non-diabetic and diabetic aged rats.. A total of 13 male aged rats (72-80 weeks old) were randomized into two groups including non-diabetic aged rats and diabetic aged rats. Diabetes was induced in aged rats by streptozotocin (single i.p. dose of 45 mg/kg body weight) administration. At the end of the 12th week, corpus cavernosum strips of rats were suspended in an organ bath system. The corpus cavernosum relaxation was evaluated by sildenafil in the presence or absence of RVT (10. Induction of diabetes resulted in significant inhibition of sildenafil-induced corpus cavernosum relaxation in aged rats. The diminished relaxation in response to sildenafil was significantly improved by acute RVT incubation in both non-diabetic and diabetic aged rats; however, the magnitude of potentiation induced by RVT was more pronounced in diabetic aged rats. The potentiating effect of RVT was significantly inhibited by L-NG-nitroarginine methyl ester (L-NAME, 10. RVT improves sildenafil-induced relaxations of corpus cavernosum in both diabetic and non-diabetic aged rats probably by potentiating the activity of NOS, and this effect seems to be more manifest in diabetic aged group.

Topics: Animals; Diabetes Mellitus, Experimental; Drug Synergism; Erectile Dysfunction; Humans; Male; Nitric Oxide; Penis; Phosphodiesterase 5 Inhibitors; Random Allocation; Rats; Rats, Wistar; Resveratrol; Sildenafil Citrate; Stilbenes

Oxidative stress dependent-decrease in nitric oxide (NO) bioavailability plays an integral role in hypercholesterolemia-induced erectile dysfunction (ED). Resveratrol has been demonstrated to exert beneficial effects against oxidative stress and improve NO bioavailability.. The protective and restorative potentials of resveratrol on endothelium-dependent relaxations were evaluated in hypercholesterolemic rabbit corpus cavernosum (CC).. Hypercholesterolemia was induced by administering 2% cholesterol diet (CD) (w/w) to the rabbits for 6 weeks. Two different protocols were applied to test the effects of resveratrol on hypercholesterolemia-induced ED. In Protocol-1 (P1), resveratrol was administrated to the rabbits simultaneously with CD in order to evaluate the protective effect, and for Protocol-2 (P2), resveratrol was administrated for 6 weeks after termination of CD in order to evaluate the restorative effect.. Endothelium-dependent relaxations of CC were evaluated by using organ bath studies. In order to elucidate the possible molecular mechanisms, we measured endothelial NO synthase (eNOS) and phosphovasodilator-stimulated phosphoprotein (VASP) expressions and activations, NADPH oxidase, superoxide dismutase (SOD), and catalase (CAT) and glutathione peroxidase (GPx) activity in cavernosal tissues obtained at the end of the study.. Resveratrol showed an improvement in the endothelium-dependent relaxation responses in vitro. We demonstrated significantly increased activatory-phosphorylation (p[S1177]-eNOS) and activated phosphovasodilator-stimulated phosphoprotein (phospho-VASP) levels, but reduced phosphorylation (p[T495]-eNOS) of eNOS and NADPH oxidase activity in the resveratrol-administered HC animals compared with hypercholesterolemic control rabbits in the P1. In the P2, resveratrol exhibited an improvement in endothelium-dependent relaxation responses and more pronounced effects on eNOS activation.. Resveratrol administration, either simultaneously with HC diet or after HC, caused an improvement in the endothelium-dependent relaxation responses in the CC, suggesting its potential in both protective and restorative purposes in hypercholesterolemic rabbit CC.

Topics: Animals; Cholesterol, Dietary; Disease Models, Animal; Endothelium; Erectile Dysfunction; Hypercholesterolemia; Male; NADPH Oxidases; Nitric Oxide; Nitric Oxide Synthase Type III; Penis; Rabbits; Resveratrol; Stilbenes

The aim of this study was to determine the effects of resveratrol on the alterations of cavernosal eNOS and LOX-1 mRNA expression in the hypercholesterolemic condition.. Twenty-one New Zealand white male rabbits were separated into three groups. Rabbits were fed with a normal dietary intake for the control group and a 2% cholesterol diet for the hypercholesterolemia and resveratrol groups for 6 weeks. Resveratrol 4 mg/kg daily was administered for the resveratrol group. Cavernosal LOX-1 and eNOS mRNA expressions were determined with real-time RT-PCR in all groups. The statistical analysis was performed with the Kruskal-Wallis and Mann-Whitney U tests.. We found no difference between mean LOX-1 mRNA expression levels in the three groups. Lower mean eNOS mRNA expression level was determined in the hypercholesterolemia group when compared with the control group (P = 0.011). Mean eNOS mRNA expression level in the resveratrol group was similar to that in the control group but significantly higher than that in the hypercholesterolemia group (P < 0.001).. This preliminary study demonstrates the beneficial effects of resveratrol on cavernosal eNOS expression. The presence of cavernosal LOX-1 expression was also shown for the first time. Resveratrol may be an alternative option in hypercholesterolemic erectile dysfunction with further studies supporting its beneficial effects on the corpus cavernosum.

Topics: Animals; Erectile Dysfunction; Hypercholesterolemia; Male; Nitric Oxide Synthase Type III; Penis; Rabbits; Resveratrol; Scavenger Receptors, Class E; Stilbenes

Despite effective control of blood glucose levels in diabetic patients, complaints of diabetes-associated erectile dysfunction (ED) persist. Resveratrol has been indicated to possess anti-diabetic effects and therapeutic potential for ED. This study was conducted to observe the effect of resveratrol alone or in combination with sildenafil on ED in streptozotocin (STZ)-induced diabetic rats.. Among 58 adult male STZ-induced (60 mg/kg) diabetic Sprague-Dawley rats, 48 STZ-induced diabetic rats were randomized equally to four groups: untreated diabetic rats, resveratrol (25mg/kg), sildenafil (5mg/kg) or resveratrol (25mg/kg) plus sildenafil (5mg/kg) through oral gavage for 8 weeks. Additionally, 12 age-matched rats were chosen as controls. Intracavernous pressure (ICP) and mean arterial blood pressure (MAP) were used to measure erectile function. The cavernous level of cyclic guanosine monophosphate (cGMP), protein and mRNA of endothelial NO synthase (eNOS), neuronal NOS (nNOS), and phosphodiesterase-5 (PDE5) was measured.. Treatment with either resveratrol or sildenafil improved ICP/MAP compared to the untreated diabetic rats (P<0.05). Treatment with resveratrol increased nNOS and eNOS expression, inhibited PDE5 expression, and increased the cavernous cGMP level compared to the untreated diabetic rats. Resveratrol significantly decreased superoxide anion and ROS production. Two-way ANOVA indicated that resveratrol in combination with sildenafil therapy had a significant synergistic effect in improving ICP/MAP and cavernous cGMP levels.. Resveratrol improves diabetes-associated ED in rats. Combination therapies with resveratrol and sildenafil have a synergistic effect in improving ED. The mechanisms might be attributed to its anti-oxidative properties and NO-cGMP signaling pathway upregulation.

Topics: Animals; Antioxidants; Blood Pressure; Cyclic GMP; Cyclic Nucleotide Phosphodiesterases, Type 5; Diabetes Complications; Diabetes Mellitus, Experimental; Erectile Dysfunction; Male; Nitric Oxide Synthase Type I; Nitric Oxide Synthase Type III; Phosphodiesterase 5 Inhibitors; Piperazines; Purines; Rats; Resveratrol; Second Messenger Systems; Sildenafil Citrate; Stilbenes; Sulfonamides

The high incidence of erectile dysfunction (ED) in diabetes highlights a need for effective treatment strategies. Resveratrol, an activator of silent information regulator 2-related enzymes 1 (sirtuin1, SIRT1), has received attention for its valuable effects in cancer, neurodegenerative diseases, longevity and cardiovascular disease. To explore the effects of resveratrol in diabetes-induced ED, resveratrol was administered to rats with streptozocin (65 mg kg(-1))-induced diabetes. Erectile function, cavernous structure, tissue protein expression of silent information regulator 2-related enzymes 1 (sirtuin1, SIRT1), p53 and forkhead transcription factor O 3a (FOXO3a), superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels in the corpora cavernosa were studied. We found that SIRT1 was expressed in cavernosal tissue, and it was downregulated in the corpora of diabetic rats. The administration of resveratrol upregulated the expression of SIRT1 and restored erectile function. In contrast, resveratrol downregulated the expression of p53 and FOXO3a, which regulate apoptosis and oxidative stress. Furthermore, the resveratrol-treated group showed an improvement in smooth muscle content, SOD activity and MDA levels when compared with the diabetic group. Therefore, the ability of resveratrol to improve diabetes-induced ED is likely related to its activation of SIRT1 expression, thus causing the suppression of apoptosis and resistance towards oxidative stress.

Topics: Animals; Diabetes Mellitus, Experimental; Down-Regulation; Erectile Dysfunction; Forkhead Box Protein O3; Forkhead Transcription Factors; Male; Penile Erection; Penis; Rats; Resveratrol; Sirtuin 1; Stilbenes; Streptozocin; Tumor Suppressor Protein p53

Phosphodiesterase type 5 (PDE5) inhibitors are very effective agents for erectile dysfunction; however, specific patient populations are hard to treat. The efficacy of PDE5 inhibitors is limited because a minimum amount of nitric oxide (NO) is necessary. Resveratrol, a plant polyphenol, is reported to activate endothelial NO synthase (eNOS) through activation of sirtuin 1. We previously reported that human corpus cavernosal smooth muscle cells (CCSMCs) express eNOS and synthesize cyclic guanosine monophosphate (cGMP) via the NO/cGMP pathway.. To investigate the ability of resveratrol and/or vardenafil to increase cGMP in an in vitro model using CCSMCs and to improve erectile function in an in vivo rat model of streptozotocin (STZ)-induced diabetes.. CCSMCs were treated with resveratrol and/or vardenafil. Twenty male Sprague-Dawley rats were randomly divided into five groups (N = 4 in each group): age-matched controls, diabetic controls, and diabetic rats treated with resveratrol, vardenafil, or both in combination for the last 4 weeks of an 8-week period of diabetes induction.. Intracellular cGMP measurement, intracovernous pressure (ICP)/mean arterial pressure (MAP) ratio, and smooth muscle/collagen ratio.. Intracellular cGMP level was elevated by resveratrol treatment in CCSMCs. The combination treatment of resveratrol and vardenafil had a synergistic effect. Diabetic rats showed impairment of erectile function. Treatment with either resveratrol or vardenafil improved ICP/MAP ratio, and combination therapy with resveratrol and vardenafil had a synergistic effect in improvement of ICP/MAP.. Treatment with either resveratrol or vardenafil elevated cGMP level in CCSMCs and improved erectile function in STZ-induced diabetic rats. Furthermore, a synergistic effect was observed in vitro and in vivo. Resveratrol or combination therapy of resveratrol and vardenafil can improve erectile function in which NO release is impaired, although further study is needed to confirm the results.

Topics: Animals; Antioxidants; Cyclic GMP; Diabetes Mellitus, Experimental; Erectile Dysfunction; Imidazoles; Male; Muscle, Smooth; Nitric Oxide; Nitric Oxide Synthase Type III; Penis; Phosphodiesterase 5 Inhibitors; Piperazines; Rats; Rats, Sprague-Dawley; Resveratrol; Stilbenes; Sulfones; Triazines; Vardenafil Dihydrochloride

This is the second of two reports of a National Institute for Occupational Safety and Health (NIOSH) Health Hazard Evaluation conducted in response to complaints of sexual dysfunction among men who manufacture the stilbene derivative 4,4'-diaminostilbene-2,2'-disulfonic acid (DAS; CAS 81-11-8), an intermediate in the manufacture of fluorescent whitening agents. The first report [Grajewski et al. (1995): Am J Ind Med 29:53-61] describes results of the analysis of reproductive hormone levels. This second report provides results from the analysis of perceived libido and potency. In a cross-sectional design, self-reported sexual function of 30 male workers who manufacture DAS and 20 former DAS workers was compared to that of 35 workers who manufactured plastics additives in a different manufacturing area. Questionnaire items were examined by factor analysis, reducing the data to these components of sexual function: sexual activity/performance (two factors), interest, satisfaction, and physiologic competence. Adjusting for age, currently exposed workers were more likely than unexposed workers to have a value in the lowest quartile for interest (adjusted odds ratio [OR] = 1.9, 95% confidence interval [CI] 0.5-7.2), physiologic competence (adjusted OR = 1.9, 95% CI 0.6-6.4), and activity/performance factor II (adjusted OR = 5.8, 95% CI 1.3-27.3). Former DAS workers reported problems associated with activity/performance factors I and II compared to unexposed workers (adjusted OR = 2.2, 95% CI 0.5-10.1 and adjusted OR = 6.7, 95% CI 1.2-35.9, respectively). Although the small study size limits the precision of the effect estimates, the pattern of results suggests a possible effect on sexual function of working in the DAS manufacturing area.

Topics: Cross-Sectional Studies; Erectile Dysfunction; Humans; Libido; Male; Middle Aged; Occupational Exposure; Stilbenes; Surveys and Questionnaires; Testosterone; Time Factors

A Health Hazard Evaluation was conducted by the National Institute for Occupational Safety and Health in an area of a large chemical plant that manufactured the stilbene derivative 4,4'-diaminostilbene-2,2'-disulfonic acid, an intermediate used for the production of optical brightening agents. Men employed in the area reported problems with impotence. The study population consisted of 44 men aged 20-57 years (mean age 37) employed in the area at the time of the evaluation. An industrial hygiene investigation, health and work history questionnaire survey, physical examinations, and blood chemistry and serum hormone evaluation were conducted. Fourteen percent of the men reported symptoms of impotence over the preceding 6 or more months, 7% had potency problems of shorter duration, and 7% were not currently impotent but had experienced impotence for 6 or more months in the past; 36% experienced decreased libido, all since beginning work in the production area. Low levels of serum testosterone (less than 350 ng/dl) were observed in 37% of the men. The low serum testosterone concentrations were not accounted for fully by diurnal variation or an effect of rotating shift work. It is suggested that exposures to chemicals possessing estrogenic activity may be related to the observed health effects in these workers.

Topics: Adult; Chemical Industry; Environmental Exposure; Erectile Dysfunction; Female; Humans; Male; Middle Aged; Occupational Diseases; Stilbenes; Surveys and Questionnaires; Testosterone

Application of the techniques of epidemiology and clinical toxicology has accelerated study of the reproductive effects of toxic chemical and physical exposures in the workplace. Three examples of work in progress are included in the present communication. The first concerns 1,2-dibromo-3-chloropropane, a known cause of male sterility, which continues to be used as a nematocide in Hawaii. Occupational exposures of Hawaiian agricultural workers to airborne 1,2-dibromo-3-chloropropane are mainly in the range of parts per billion. A prospective study of pineapple field workers has been undertaken to evaluate sperm counts and morphology before, during, and after 1,2-dibromo-3-chloropropane application. To date, no sperm count depression is evident at this level of exposure. The second example involves a cluster of seven spontaneous abortions in female office workers exposed to video display terminals. The cluster has been analyzed with the use of fetal life tables. Excess incidence was confirmed (p = 0.0045), but no etiology was determined. The findings may have been due to chance. The third example pertains to male chemical workers manufacturing diaminostilbene, an optical brightener, and the workers' reported sexual impotence. Impotence was confirmed in 7 of 29 workers by questionnaire and suggested for another 7. Serum testosterone analyses found depressed values (less than 300 mg/ml) in 8 of 28 exposed workers. The luteinizing hormone and follicular stimulating hormone levels were generally normal.

Topics: Abortion, Spontaneous; Data Display; Environmental Health; Erectile Dysfunction; Female; Humans; Infertility, Male; Male; National Institute for Occupational Safety and Health, U.S.; Pregnancy; Propane; Reproduction; Stilbenes; United States