Saturday, 2 November 2013

4 Foods 4 Longevity and Diseases Free (2) - Grape Seeds and Skins

Over the years of research, 4 foods appeared mostly in medical studies in preventing and treating diseases, are Green Tea, Grape seed and skin, Turmeric and Soy. All Right Reserved.

Grape is a woody vines of the genus Vitis, belong to the family Vitaceae, native to southern Turkey.
A. Quoted From The World Most Popular Herbs
Grape Seed Extract is the commercial extracts from whole grape seeds that contains many concentrations, including vitamin E, flavonoids, linoleic acid, oligomeric proanthocyanidins(OPCs), etc..The herb has been used in traditional medicine as antioxidant, anti-inflammatory agents and to treat skin wounds with less scarring, allergies, macular degeneration, arthritis, enhance circulation of blood vessels, lower cholesterol, etc.

1. Ulcer
in the comparison of effects of Grape Seed Extract (GSE) and vitamins C and E on aspirin- and ethanol-induced gastric ulcer and associated increases of lipid peroxidation in rats, found that GSE protected against ethanol-induced gastric ulcers more effectively than VC or VE, while its protection against aspirin ulcers was comparable for all treatments. GSE produced the greatest reductions of gastric MDA in both models, according to" Effects of grape seed extract, vitamin C, and vitamin e on ethanol- and aspirin-induced ulcers" by Cuevas VM, Calzado YR, Guerra YP, Yera AO, Despaigne SJ, Ferreiro RM, Quintana DC.(1)

2. Pulmonary fibrosis
in assessment of grape seed extract (GSE) or vitamin E (Vit E) as antioxidants in effecting oxidative stress implication in the pathogenesis of silica-induced lung fibrosis indicated that according to the results of this study GSE could reduce the fibrogenic effect of silica. However; no synergistic effect was observed after co-administration of GSE and Vit E, according to "A comparative study of grape seed extract and vitamin E effects on silica-induced pulmonary fibrosis in rats" by Hemmati AA, Nazari Z, Samei M.(2)

3. Liver protective effect
In the observation of the efficacy of methotrexate (MTX), a widely used cytotoxic chemotherapeutic agent, and its liver protective effect found that GSE was supplemented, no significant changes in blood count parameters were noted. It appears that GSE protects the rat liver and inhibits methotrexate-induced oxidative stress. These data indicate that GSE may be of therapeutic benefit when used with MTX, according to "Role of grape seed extract on methotrexate induced oxidative stress in rat liver" by Cetin A, Kaynar L, Kocyigit I, Hacioglu SK, Saraymen R, Ozturk A, Sari I, Sagdic O.(3)

4. Antioxidant Activity
in the assessment of phenolic content, antioxidant activity of White and red wines spiked with green tea extract and grape seed extract found that the green tea extract and grape seed extract increased antioxidant activity dose-dependently and the CRTs varied considerably between the Korean and Australian groups, with Koreans preferring wines spiked with green tea extract and Australians showing a preference for wines spiked with grape seed extract, according to "Total Phenolic Content, Antioxidant Activity and Cross-Cultural Consumer Rejection Threshold in White and Red Wines Functionally Enhanced with Catechin-Rich" by Yoo YJ, Saliba A, Prenzler PD, Ryan DM.(4)

5. Skin Photoprotection
In the study of polyphenols distributed in plant foods, such as, fruits, vegetables, nuts, flowers, bark and seeds, etc., found that the selected polyphenols include: green tea polyphenols, pomegranate fruit extract, grape seed proanthocyanidins, resveratrol, silymarin, genistein and delphinidin. The new information on the mechanisms of action of these polyphenols supports their potential use in skin photoprotection and prevention of photocarcinogenesis in humans, according to "Polyphenols: Skin Photoprotection and Inhibition of Photocarcinogenesis" by Afaq F, Katiyar SK.(5)

6. Renal Ischemia/Reperfusion Injuries
In the evaluation of grape seed proanthocyanidin extract (GSPE) protects against renal I/R injury found that GSPE significantly reduced increases in urea, creatinine and cystatin C; increased kidney superoxide dismutase activity and glutathione peroxidase levels and reduced malondialdehyde levels. GSPE reduced histological renal damage and nuclear factor-κB activity. These results suggest that GSPE reduces renal dysfunction and injury caused by renal I/R, according to "Grape Seed Proanthocyanidin Extract Reduces Renal Ischemia/Reperfusion Injuries in Rats" by Wei R, Ding R, Wang Y, Tang L.(6)

7. Anticancers
a. In the reviews of Grapes and grape-based products as one such class of dietary products and its cancer chemopreventive potential, indicated that Overall, completed studies from various scientific groups conclude that both grapes and grape-based products are excellent sources of various anticancer agents and their regular consumption should thus be beneficial to the general population, according to "Anticancer and cancer chemopreventive potential of grape seed extract and other grape-based products" by Kaur M, Agarwal C, Agarwal R.(7a)

b. In the study of the biological and chemopreventive activities of grape seed polyphenols and its inhibition of either initiation or promotion/progression stages of carcinogenesis found that suggest that the chemopreventive activity of polyphenols extracted from seedless grape cultivars was as effective as that of the seeded variety and these may have beneficial effects in disease states, especially cancer, according to "Antitumor-promoting effects of polyphenolic extracts from seedless and seeded Indian grapes" by Ramchandani AG, Karibasappa GS, Pakhale SS.(7b)

8. Colon Cancer
In the investigation of polyphenols of grape waste and its protection against human diseases related to oxidative stress, such as colorectal cancer, found that the grape extract has a significant antiproliferative effect in a tumor cell line. These data indicate that grape extract is a promising product to be used as an anti-free radical agent and could exert a chemopreventive action, according to "Grape waste extract obtained by supercritical fluid extraction contains bioactive antioxidant molecules and induces antiproliferative effects in human colon adenocarcinoma cells" by Lazzè MC, Pizzala R, Gutiérrez Pecharromán FJ, Gatòn Garnica P, Antolín Rodríguez JM, Fabris N, Bianchi L.(8)
9. Prostate cancer
In the analyzing the bioflavonoids from Grape seed extract (GSE) and theirs effect on prostate cancer (PCA) found that that GSE possibly causes mitochondrial damage leading to cytochrome c release in cytosol and activation of caspases resulting in PARP cleavage and execution of apoptotic death of human PCA DU145 cells. Furthermore, GSE-caused caspase 3-mediated apoptosis also involves other pathway(s) including caspase 9 activation, according to "Grape seed extract induces apoptotic death of human prostate carcinoma DU145 cells via caspases activation accompanied by dissipation of mitochondrial membrane potential and cytochrome c release" by Agarwal C, Singh RP, Agarwal R.(9)

10. Atherosclerosis
in the association of consumption of red wine and other polyphenolic compounds and prevention of cardiovascular diseases found that aortic atherosclerosis evaluated as the cholesterol content in aortic tissue was comparable in the control and GSE-dosed females, but it was significantly reduced in the abdominal part of GSE-dosed male compared to the controls (P < 0.05). In conclusion, feeding GSE extract to Watanabe heritable hyperlipidemic (WHHL) rabbits had no significant effects in females but was associated with transient less hypercholesterolemic response to semisynthetic diet, according to "Effects of red grape skin and seed extract supplementation on atherosclerosis in Watanabe heritable hyperlipidemic rabbits" by Frederiksen H, Mortensen A, Schrøder M, Frandsen H, Bysted A, Knuthsen P, Rasmussen SE.(10)

11. Arthritis (CIA)
in the examination of whether grape seed proanthocyanidin extract (GSPE) effect on collagen-induced arthritis (CIA) in mice found that GSPE dose-dependently suppressed osteoclastogenesis in vitro. GSPE significantly reduced hydrogen peroxide production by anti-CD3-monoclonal-antibody-stimulated CD4+ splenocytes. These results indicate that intraperitoneal injection of GSPE attenuated CIA in mice. GSPE may be useful in the treatment of rheumatoid arthritis, according to "Grape seed proanthocyanidin extract (GSPE) attenuates collagen-induced arthritis" by Cho ML, Heo YJ, Park MK, Oh HJ, Park JS, Woo YJ, Ju JH, Park SH, Kim HY, Min JK.(11)

12. Etc.

Healthy Happy Herbs
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B. Quoted From Phytochemicals in Foods
B.1. Resveratrol is a phytochemical in the class of Stilbenoids, found abundantly in skins and seed of grape wine, nuts, peanuts, etc.
1. Anti cancers
In the review of resveratrol and it effects as a chemopreventive agent, tumor initation, promotion, and progression via multiple pathways, indicated that resveratrol exerts antioxidant activities, hence contributing to the prevention of tumor initiation. Growing or metastasizing carcinomas are inhibited by resveratrol through prevention of angiogenesis by inhibiting VEGF and matrix metalloproteases. Induction of apoptosis and cell cycle arrest, important mechanisms for cancer therapy, are stimulated by resveratrol through different mechanisms, e.g., activation of p53 and modulation of cell cycle proteins, according to "Fighting cancer with red wine? Molecular mechanisms of resveratrol" by Kraft TE, Parisotto D, Schempp C, Efferth T.(1)

2. Anti cancers and anti inflammatory effects
In the observation of Resveratrol's effects in exhibition of several physiological activities including anticancer and anti-inflammatory activities in vitro and in experimental animal models, as well as in humans, found that Anticancer activity of this compound is mainly due to induction of apoptosis via several pathways, as well as alteration of gene expressions, all leading to a decrease in tumor initiation, promotion, and progression. Resveratrol exhibits anti-inflammatory activity through modulation of enzymes and pathways that produce mediators of inflammation and also induction of programmed cell death in activated immune cells. Resveratrol has been shown to produce no adverse effects, even when consumed at high concentrations, according to "Potential of resveratrol in anticancer and anti-inflammatory therapy" by Udenigwe CC, Ramprasath VR, Aluko RE, Jones PJ.(2)

3. Prostate cancer
In the evaluation of
the tumor suppressor gene PTEN (phosphatase and tensin homolog deleted on chromosome 10) and the androgen receptor (AR) in tumor development and progression in prostate carcinogenesis, found that resveratrol may act as potential adjunctive treatment for late-stage hormone refractory prostate cancer. More importantly, for the first time, our study demonstrates the mechanism by which AR regulates PTEN expression at the transcription level, indicating the direct link between a nuclear receptor and the PI3K/AKT pathway, according to "Resveratrol regulates the PTEN/AKT pathway through androgen receptor-dependent and -independent mechanisms in prostate cancer cell lines' by
Wang Y, Romigh T, He X, Orloff MS, Silverman RH, Heston WD, Eng C.(3)

4. Cardiovascular diseases
In the revie of reviews some of the key studies, and the known mechanisms for these beneficial effects. Evidence from different experimental studies, including from the authors' laboratories, and the beneficial effects of polyphenols found in red wine, especially resveratrol in grape skins.
found that Resveratrol benefits include a reduction in cardiovascular morbidity and mortality, lung cancer and prostate cancer by approximately 30% to 50%, 57% and 50%, respectively. Polyphenols possess antioxidant, superoxide-scavenging, ischemic-preconditioning and angiogenic properties. Some of these properties of polyphenols may explain their protective effects on the cardiovascular system, as well as other body organs, according to "Significance of wine and resveratrol in cardiovascular disease: French paradox revisited" by

Vidavalur R, Otani H, Singal PK, Maulik N.(4)

5. Cardiovascular health
In the review of Resveratrol (3,4',5-trihydroxystilbene), a member of natural, plant-derived chemicals known as polyphenols and is attracting increased attention due to its diverse health benefits especially in case of cardiovascular disease, cancer, diabetes and neurological problems, indicated that Recently, resveratrol was found to induce autophagy and regenerate myocardial ischemic tissue treated with stem cells. Overall observation indicates that resveratrol has a high therapeutic potentials for the treatment of cardiovascular diseases, according to "Resveratrol and cardiovascular health" by Das M, Das DK.(5)

6. Anti inflammatory effects
In the study of implantation and growth of metastatic cancer cells at distant organs is promoted by inflammation-dependent mechanism, found that resveratrol remarkably inhibited hepatic retention and metastatic growth of melanoma cells by 50% and 75%, respectively. The mechanism involved IL-18 blockade at three levels: First, resveratrol prevented IL-18 augmentation in the blood of melanoma cell-infiltrated livers. Second, resveratrol inhibited IL-18-dependent expression of VCAM-1 by tumor-activated hepatic sinusoidal endothelium, preventing melanoma cell adhesion to the microvasculature. Third, resveratrol inhibited adhesion- and proliferation-stimulating effects of IL-18 on metastatic melanoma cells through hydrogen peroxide-dependent nuclear factor-kappaB translocation blockade on these cells, according to "Resveratrol prevents inflammation-dependent hepatic melanoma metastasis by inhibiting the secretion and effects of interleukin-18" by Salado C, Olaso E, Gallot N, Valcarcel M, Egilegor E, Mendoza L, Vidal-Vanaclocha F.(6)

7. Oxidative stress and endothelial dysfunction
In the investiagtion of the role of S6K1 in aging-associated endothelial dysfunction and effects of the polyphenol resveratrol on S6K1 in aging endothelial cells, wrote that our data demonstrate a causal role of the hyperactive S6K1 in eNOS uncoupling leading to endothelial dysfunction and vascular aging. Resveratrol improves endothelial function in aging, at least in part, through inhibition of S6K1. Targeting S6K1 may thus represent a novel therapeutic approach for aging-associated vascular disease, according to "Hyperactive S6K1 mediates oxidative stress and endothelial dysfunction in aging: inhibition by resveratrol" by Rajapakse AG, Yepuri G, Carvas JM, Stein S, Matter CM, Scerri I, Ruffieux J, Montani JP, Ming XF, Yang Z.(7)

8. Insulin resistance
In the evaluation of the effects of Res on insulin sensitivity and the underlying mechanism, insulin-resistant KKA(y) mice were treated with 2 and 4 g/kg diets of Res for 12 weeks, found that Res intervention reduces blood glucose and serum insulin levels, improves insulin and glucose tolerance, increases serum adiponectin and adiponectin mRNA levels in epididymal adipose tissues, and more importantly, elevates Sirt1, p-AMPK, p-IRS1, and p-AKT levels in liver and soleus muscles, according to "Effects of resveratrol on the amelioration of insulin resistance in KKA(y) mice" by Chen S, Li J, Zhang Z, Li W, Sun Y, Zhang Q, Feng X, Zhu W.(8)

9. Propionibacterium acnes
In the investigation of whether P. acnes biofilms could be eradicated by plant extracts or their active compounds, and whether other mechanisms besides killing of biofilm cells could be involved, found that out of 119 plant in the study, researchers identified five with potent antibiofilm activity against P. acnes (extracts from Epimedium brevicornum, Malus pumila, Polygonum cuspidatum, Rhodiola crenulata and Dolichos lablab). We subsequently identified icariin, resveratrol and salidroside as active compounds in three of these extracts. Extracts from E. brevicornum and P. cuspidatum, as well as their active compounds (icariin and resveratrol, respectively) showed marked antibiofilm activity when used in subinhibitory concentrations, indicating that killing of microbial cells is not their only mode of action, accoridng to "Eradication of Propionibacterium acnes biofilms by plant extracts and putative identification of icariin, resveratrol and salidroside as active compounds" by Coenye T, Brackman G, Rigole P, De Witte E, Honraet K, Rossel B, Nelis HJ.(9)

10. Healthy heart and longevity
In the review focuses on the anti-aging aspects of resveratrol, the possible mechanisms of action,
found that resveratrol can induce the expression of several longevity genes including Sirt1, Sirt3, Sirt4, FoxO1, Foxo3a and PBEF and prevent aging-related decline in cardiovascular function including cholesterol level and inflammatory response, but it is unable to affect actual survival or life span of mice, according to "Resveratrol and red wine, healthy heart and longevity" by Das DK, Mukherjee S, Ray D.(10)

11. Antioxidants
In the assessment of the effects of the antioxidants resveratrol and quercetin on frozen-thawed ram sperm, found that Semen samples (which exceeded minimum standards) from four mature crossbreed Santa Inês rams were pooled and aliquots of each pool were diluted in Tris-egg yolk-glycerol, with the addition of 0, 5, 10, 15, and 20 μg/mL of resveratrol and quercetin in Experiment 1 and Experiment 2, respectively. In Experiment 1, the proportion of sperm with a high mitochondrial membrane potential was greater (P < 0.02) in the control group than in resveratrol 20 μg/mL group. In Experiment 2, the proportion of sperm with high mitochondrial membrane potential was greater in the control group (P < 0.0001) than in the other experimental groups, and greater in the quercetin 5 μg/mL group (P < 0.05) than in the other quercetin-treated groups, according to "Effect of antioxidants resveratrol and quercetin on in vitro evaluation of frozen ram sperm" by Silva EC, Cajueiro JF, Silva SV, Soares PC, Guerra MM.(11)

12. Incision-induced acute and chronic pain
In the searching for more efficacious treatments in inhibition of incision-induced pain and prevention of the transition to chronic pain following surgery, found that local injection of resveratrol around the surgical wound strongly attenuates incision-induced allodynia. Intraplantar IL-6 injection and plantar incision induces persistent nociceptive sensitization to PGE2 injection into the affected paw after the resolution of allodynia to the initial stimulus. We further show that resveratrol treatment at the time of IL-6 injection or plantar incision completely blocks the development of persistent nociceptive sensitization consistent with the blockade of a transition to a chronic pain state by resveratrol treatment, according to "Resveratrol engages AMPK to attenuate ERK and mTOR signaling in sensory neurons and inhibits incision-induced acute and chronic pain" by Tillu DV, Melemedjian OK, Asiedu MN, Qu N, De Felice M, Dussor G, Price TJ.(12)

13. Anti diabetes
In the evaluation of resveratrol, a polyphenolic SIRT1 activator and its SIRT1 activation in an in vitro fluorescent based assay (EC(50) : 7 μM) and the efficacy of resveratrol was also evaluated in ob/ob mice for its antidiabetic and associated metabolic effects, found that a significant improvement observed in the glucose excursion in the oral glucose tolerance test performed for 120 min; although an insignificant improvement in the triglycerides, total cholesterol, adiponectin and free fatty acid levels was observed at different doses of resveratrol tested. The present findings suggest that resveratrol is an antihyperglycemic agent and drugs similar to resveratrol can be considered as an effective therapeutic adjuvant for the current treatment of diabetes mellitus, according to "Antidiabetic activity of resveratrol, a known SIRT1 activator in a genetic model for type-2 diabetes" by Sharma S, Misra CS, Arumugam S, Roy S, Shah V, Davis JA, Shirumalla RK, Ray A.(13)

14. Neuroprotective effects
In the
elucidation of the neuroprotective effect and influence of resveratrol on the extracellular levels of neurotransmitter and neuromodulator during ischemia/reperfusion in rats,
found that chronic treatment with resveratrol remarkably reduced the release of excitatory neurotransmitter glutamate, aspartate and neuromodulator d-Serine during ischemia and reperfusion; and significantly increased the basal extracellular levels of inhibitory neurotransmitter gamma-amino-n-butyric acid, glycine and taurine. Chronic treatment with resveratrol also ameliorated O-phosphoethanolamine levels and excitotoxic index during ischemia and reperfusio, according to "Neuroprotective effects of resveratrol on ischemic injury mediated by modulating the release of neurotransmitter and neuromodulator in rats" by Li C, Yan Z, Yang J, Chen H, Li H, Jiang Y, Zhang Z(14)

15. Neuroprotective effects
In the investigation of the neuroprotective properties of resveratrol found that Resveratrol has neuroprotective features both in vitro and in vivo in models of Alzheimer's disease (AD), but it has proved to be beneficial also in ischemic stroke, Parkinson's disease, Huntington's disease, and epilepsy, according to "Neuroprotective properties of resveratrol in different neurodegenerative disorders" by Albani D, Polito L, Signorini A, Forloni G.(15)

16. Etc.

Pterostilbene is a phytochemical in the class of Stilbenoids, found abundantly in grapes, blueberries, etc.
1. Colon cancer
In the identification of the chemopreventive potential of pterostilbene with colonic tumor formation as an end point and further to evaluate the mechanistic action of pterostilbene during colon carcinogenesis, found that Colon tumors from pterostilbene-fed animals showed reduced expression of inflammatory markers as well as nuclear staining for phospho-p65, a key molecule in the nuclear factor-kappaB pathway. In HT-29 cells, pterostilbene reduced the protein levels of beta-catenin, cyclin D1 and c-MYC, altered the cellular localization of beta-catenin and inhibited the phosphorylation of p65, according to "Dietary intake of pterostilbene, a constituent of blueberries, inhibits the beta-catenin/p65 downstream signaling pathway and colon carcinogenesis in rats' by Paul S, DeCastro AJ, Lee HJ, Smolarek AK, So JY, Simi B, Wang CX, Zhou R, Rimando AM, Suh N.(1)

2. Antioxidant effect
In the study of the antioxidant activities of trans-resveratrol, pterostilbene and quercetin, and the effect of their combination were investigated in human erythrocytes in vitro, found that Resveratrol was significantly less effective. However, the three compounds protected the erythocytes against hemolysis and GSH (reduced glutathione) depletion to the same extent. Combinations consisting of two compounds (molar ratio 1:1) influenced lipid peroxidation in a concentration-dependent manner. At lower concentrations, resveratrol with quercetin or pterostilbene inhibited synergistically the oxidative injury of membrane lipids At higher concentrations, an additive effect was observed, according to "Antioxidant effect of trans-resveratrol, pterostilbene, quercetin and their combinations in human erythrocytes in vitro" by Mikstacka R, Rimando AM, Ignatowicz E.(2)

3. Breast cancer
In the study of receptor pathways- estrogen receptor (ER) and tyrosine kinase receptors, especially the epidermal growth factor receptor (EGFR) family and theirs effects on cell-proliferation and in the development of both primary and recurrent breast cancer,
indicated that there is strong evidence to show that several phytochemicals present in berries such as cyanidin, delphinidin, quercetin, kaempferol, ellagic acid, resveratrol and pterostilbene, interact with and alter the effects of these pathways, according to " Influence of Berry-Polyphenols on Receptor Signaling and Cell-Death Pathways: Implications for Breast Cancer Prevention" by Aiyer H, Warri AM, Woode DR, Hilakivi-Clarke L, Clarke R.(3)

4. Anti-adipogenic effects
In the assessment of the effects of garcinol and pterostilbene on cell proliferation and adipogenesis in 3T3-L1 cells, found that garcinol and pterostilbene caused an inhibition of lipid accumulation in the 3T3-L1 adipocyte differentiation phase. Garcinol and pterostilbene also significantly up-regulated the gene expression of adiponectin as well as down-regulated the gene expressions of leptin, resistin, and fatty acid synthase (FAS) in 3T3-L1 adipocyte differentiation. In 3T3-L1 adipocytes, garcinol significantly down-regulated the protein expressions of PPARγ and FAS as well as up-regulated the protein expressions of adipose triglyceride lipase (ATGL) and adiponectin, according to "Inhibitory effects of garcinol and pterostilbene on cell proliferation and adipogenesis in 3T3-L1 cells" by Hsu CL, Lin YJ, Ho CT, Yen GC.(4)

5. Aging and Alzheimer's disease
In the investigation of resveratrol and pterostilbene, a resveratrol derivative, in the protection against age-related diseases including Alzheimer's disease (AD), found that two months of pterostilbene diet but not resveratrol significantly improved radial arm water maze function in SAMP8 compared with control-fed animals. Neither resveratrol nor pterostilbene increased sirtuin 1 (SIRT1) expression or downstream markers of sirtuin 1 activation. Importantly, markers of cellular stress, inflammation, and AD pathology were positively modulated by pterostilbene but not resveratrol and were associated with upregulation of peroxisome proliferator-activated receptor (PPAR) alpha expression, according to "Low-dose pterostilbene, but not resveratrol, is a potent neuromodulator in aging and Alzheimer's disease" by Chang J, Rimando A, Pallas M, Camins A, Porquet D, Reeves J, Shukitt-Hale B, Smith MA, Joseph JA, Casadesus G.(5)

6. Cholesterol
In the investigation of whether resveratrol and its three analogues (pterostilbene, piceatannol, and resveratrol trimethyl ether) would activate the peroxisome proliferator-activated receptor alpha (PPARalpha) isoform, found that the maximal luciferase activity responses to pterostilbene were higher than those obtained with the hypolipidemic drug, ciprofibrate (33910 and 19460 relative luciferase units, respectively), at 100 microM. Hypercholesterolemic hamsters fed with pterostilbene at 25 ppm of the diet showed 29% lower plasma low density lipoprotein (LDL) cholesterol, 7% higher plasma high density lipoprotein (HDL) cholesterol, and 14% lower plasma glucose as compared to the control group. The LDL/HDL ratio was also statistically significantly lower for pterostilbene, as compared to results for the control animals, at this diet concentration, according to "Pterostilbene, a new agonist for the peroxisome proliferator-activated receptor alpha-isoform, lowers plasma lipoproteins and cholesterol in hypercholesterolemic hamsters" by Rimando AM, Nagmani R, Feller DR, Yokoyama W.(6)

7. Atherosclerosis
In the determination of the effect of Pterostilbene (PT) on Vascular endothelial cell (VEC) apoptosis, the main event occurring during the development of atherosclerosis, found that Cotreatment with PT and siRNA of LOX-1 synergistically reduced oxLDL-induced apoptosis in HUVECs. Overexpression of LOX-1 attenuated the protection by PT and suppressed the effects of PT on oxLDL-induced oxidative stress. PT may protect HUVECs against oxLDL-induced apoptosis by downregulating LOX-1-mediated activation through a pathway involving oxidative stress, p53, mitochondria, cytochrome c and caspase protease. PT might be a potential natural anti-apoptotic agent for the treatment of atherosclerosis, according to "Pterostilbene protects vascular endothelial cells against oxidized low-density lipoprotein-induced apoptosis in vitro and in vivo" by Zhang L, Zhou G, Song W, Tan X, Guo Y, Zhou B, Jing H, Zhao S, Chen L.(7)

8. Adjuvant arthritis
In the evaluation of the effects of pinosylvin (PIN) and pterostilbene (PTE), natural substances from the stilbenoid group, on the development of adjuvant arthritis in rats, found that the effect of PTE on CL was only partial. PIN, on the other hand, had a beneficial anti-inflammatory and antioxidant effect on oxidative stress induced biochemical changes occurring in AA, as determined by all three functional parameters, according to "In vivo effect of pinosylvin and pterostilbene in the animal model of adjuvant arthritis" by Macickova T, Drabikova K, Nosal R, Bauerova K, Mihalova D, Harmatha J, Pecivova J.(8)

9. Bladder cancer
In the study of Pterostilbene (PT), a naturally occurring phytoalexin, and its effects in a variety of pharmacologic activities, including antioxidant, cancer prevention activity and cytotoxicity to many cancers, found that PT causes autophagy in cancer cells and suggests that PT could serve as a new and promising agent for the treatment of sensitive and chemoresistant bladder cancer cells, according to "Pterostilbene induces autophagy and apoptosis in sensitive and chemoresistant human bladder cancer cells" by Chen RJ, Ho CT, Wang YJ.(9)

10. Anti-inflammatory effects
In the examination of the molecular mechanisms of the action of pterostilbene in colon cancer,
indicated that A combination of cytokines (tumor necrosis factor-alpha, IFN-gamma, and bacterial endotoxin lipopolysaccharide) induced inflammation-related genes such as inducible nitric oxide synthase and cyclooxygenase-2, which was significantly suppressed by treatment with pterostilbene. We further identified upstream signaling pathways contributing to the anti-inflammatory activity of pterostilbene by investigating multiple signaling pathways, including nuclear factor-kappaB, Janus-activated kinase-signal transducer and activator of transcription, extracellular signal-regulated kinase, p38, c-Jun NH(2)-terminal kinase, and phosphatidylinositol 3-kinase, according to "Anti-inflammatory action of pterostilbene is mediated through the p38 mitogen-activated protein kinase pathway in colon cancer cells" by Paul S, Rimando AM, Lee HJ, Ji Y, Reddy BS, Suh N.(10)

11. Etc.
B.3. Piceatannol
Piceatannol is a phytochemical in the class of Stilbenoids, found abundantly in grapes, etc.
1. Anti cancers
In the determination of the apoptotic effects of piceatannol and myricetin, naturally occurring polyphenols in red wine, alone or in combination, in two human cell lines: HL-60 (leukemia) and HepG2 (hepatoma), found that on the signaling pathways responsible for induction of HO-1 expression.found that piceatannol or myricetin alone induced apoptotic cell death in a concentration- and time-dependent manners in HL-60 cells. Furthermore, in combined treatment the percentage of apoptotic HL-60 cells was significantly higher. Nevertheless, the percentage of TUNEL positive HepG2 cells only was significant after piceatannol treatment and in combined treatment was even lower than in cells treated with piceatannol alone, according to "Selective apoptotic effects of piceatannol and myricetin in human cancer cells" by Morales P, Haza AI.(1)

2. Breast cancer
found that PIC inhibited migration and anchorage-independent growth of human mammary epithelial cells (MCF-10A) treated with the prototypic tumor promoter, 12-O-tetradecanoylphorbol-13-aceate (TPA). PIC treatment suppressed the TPA-induced activation of NF-kappaB and expression of cyclooxygenase-2 (COX-2) in MCF-10A cells. We speculate that an electrophilic quinone formed as a consequence of oxidation of PIC bearing the catechol moiety may directly interact with critical cysteine thiols of IKKbeta, thereby inhibiting its catalytic activity "Piceatannol, a catechol-type polyphenol, inhibits phorbol ester-induced NF-{kappa}B activation and cyclooxygenase-2 expression in human breast epithelial cells: cysteine 179 of IKK{beta} as a potential target" by Son PS, Park SA, Na HK, Jue DM, Kim S, Surh YJ.(2)

3. Anti-inflammatory activities and cardioprotective effect
In the investigation of the modulation of inflammation by resveratrol and its metabolites by determining the expression and release of chemokine, eotaxin-1, in cultured human pulmonary artery endothelial cells, found that piceatannol showed potency similar to resveratrol. We propose that control of eotaxin-1 expression and release by proinflammatory cytokines in HPAEC may be considered as an in vitro model for screening and discovering polyphenols with anti-inflammatory activities and cardioprotective potentials, according to "Control of eotaxin-1 expression and release by resveratrol and its metabolites in culture human pulmonary artery endothelial cells" by Yang CJ, Lin CY, Hsieh TC, Olson SC, Wu JM.(3)

4. Alzheimer's disease
In the demonstration of the presence of autoantibodies to ecto-F1-ATPase (ASabs) in sera and cerebrospinal fluids from patients with Alzheimer's disease (AD), found that ASabs, unlike irrelevant antibodies, can increase cellular uptake of HDL, a risk factor for the development of AD, via a mechanism involving the prototypical function of ecto-F1-ATPase: the generation of ADP due to the hydrolysis of ATP. Piceatannol, a specific inhibitor ecto-F1-ATPase, completely hindered these effects. We hypothesize that ASabs could exert a pathogenetic role in AD, according to "Anti-ATP synthase autoantibodies from patients with Alzheimer's disease reduce extracellular HDL level" by Vacirca D, Barbati C, Scazzocchio B, Masella R, Rosano G, Malorni W, Ortona E.(4)

5. Prostate cancer
In the determination of whether piceatannol inhibits the lung metastasis of prostate cancer cells, MAT-Ly-Lu (MLL) rat prostate cancer cells expressing luciferase were injected into the tail veins of male nude mice, found that Piceatannol increased the protein levels of tissue inhibitor of metalloproteinase-2 in a concentration-dependent fashion. Additionally, piceatannol inhibited the phosphorylation of signal transducer and activator of transcription (STAT) 3. Furthermore, piceatannol effected reductions in both basal and EGF-induced interleukin (IL)-6 secretion. An IL-6 neutralizing antibody inhibited EGF-induced STAT3 phosphorylation and EGF-stimulated migration of DU145 cells. Interleukin-6 treatment was also shown to enhance the secretion of uPA and VEGF, STAT3 phosphorylation and the migration of DU145 cells; these increases were suppressed by piceatannol. These results demonstrate that the inhibition of IL-6/STAT3 signaling may constitute a mechanism by which piceatannol regulates the expression of proteins involved in regulating the migration and invasion of DU145 cells, according to "Piceatannol inhibits migration and invasion of prostate cancer cells: possible mediation by decreased interleukin-6 signaling" by Kwon GT, Jung JI, Song HR, Woo EY, Jun JG, Kim JK, Her S, Park JH.(5)

6. Antiallergic and radical scavenging activities
In the assessment of the methanolic extract of the whole plant of Cyperus longus originating in Egypt and its antiallergic effect on ear passive cutaneous anaphylaxis reactions in mice,
found that Among the isolates, longusol B (IC(50)=96 µM), luteolin (3.0 µM), resveratrol (17 µM), piceatannol (24 µM), and cassigarols E (84 µM) and G (84 µM) were found to inhibit the release of β-hexosaminidase, as a marker of antigen-induced degranulations, in rat basophilic leukemia (RBL-2H3) cells, accoridng to "Structures of novel norstilbene dimer, longusone A, and three new stilbene dimers, longusols A, B, and C, with antiallergic and radical scavenging activities from Egyptian natural medicine Cyperus longus" by Morikawa T, Xu F, Matsuda H, Yoshikawa M.(6)

7. Anti aging
In the review of the cellular senescence, characterized by cellular hypertrophy: cell growth in the absence of cell division, indicated that the genes that regulate this process can be activated or inactivated by numerous plant polyphenols such as resveratrol, quercetin, butein, fistein, piceatannol, curcumin. Many of these substances have been shown to lengthen the lifespan of invertebrates. Many of these compounds have other potential beneficial effects on lifespan as antiatherogenic or antineoplastic agents, according to "The potential influence of plant polyphenols on the aging process" by Cherniack EP.(7)

8. Melanogenesis and collagen synthesis
In the evaluation of The effect of passion fruit, the fruit of Passiflora edulis , on melanin inhibition and collagen synthesis, using cultured human melanoma and fibroblast cells, found that treatment of melanoma cells with PF-S led to inhibition of melanogenesis. In addition, the production of total soluble collagen was elevated in dermal fibroblast cells cultured in the presence of PF-S. PF-R and PF-P did not yield these effects. Furthermore, the removal of polyphenols from PF-S led to the abolishment of the effects described above. We discovered that piceatannol (3,4,3',5'-tetrahydroxy-trans-stilbene) is present in passion fruit seeds in large amounts and that this compound is the major component responsible for the PF-S effects observed on melanogenesis and collagen synthesis, according to "Extract of Passion Fruit ( Passiflora edulis ) Seed Containing High Amounts of Piceatannol Inhibits Melanogenesis and Promotes Collagen Synthesis" by Matsui Y, Sugiyama K, Kamei M, Takahashi T, Suzuki T, Katagata Y, Ito T.(8)

9. Colitis
In the investigation of the possible protective effects of resveratrol and piceatannol against dextran sulfate sodium (DSS)-induced inflammation in mouse colonic mucosa, found that oral administration of resveratrol or piceatannol (10 mg/kg body weight each) for 7 constitutive days attenuated the DSS-induced inflammatory injury, upregulation of iNOS expression, and activation of NF-kappaB, STAT3, and ERK, according to "Resveratrol and piceatannol inhibit iNOS expression and NF-kappaB activation in dextran sulfate sodium-induced mouse colitis" by Youn J, Lee JS, Na HK, Kundu JK, Surh YJ.(9)

10. Etc.

C. Quoted From Foods to prevent and treat diseases
1. Acne
Grapes Resveratrol is a phytochemical in the class of Stilbenoids, found abundantly in skins and seed of grape. Dr. Fabbrocini G,and the scientists at the University of Naples Federico in the study of resveratrol-containing hydrogel administered to 20 patients affected by acne vulgaris enrolled in this single-blind study, showed  a 53.75% mean reduction in the GAGS score on the resveratrol-treated sides of the face compared with 6.10% on the vehicle-treated sides of the face. These data were supported by histologic analysis, which showed a 66.7% mean reduction in the average area of microcomedones on the resveratrol-treated sides of the face. The comparison with the vehicle-treated side of the face (9.7% reduction) showed a clinically relevant and statistically significant decrease of lesions in areas treated with resveratrol-containing hydrogel(1).

2. Anxiety
In the study  to determine the effect of resveratrol on hippocampal damage and behavioral deficits in 7-day-old rat pups subjected to contusion injury, showed that  treatment with resveratrol decreased anxiety and increased cortex/hippocampus dependent memory of animals subjected to blunt head trauma. These results show that acute treatment of resveratrol has a neuroprotective role against trauma induced hippocampal neuron loss and associated cognitive impairment in rats(2).

3. Alzheimer's disease
Resveratrol is a phytochemical in the class of Stilbenoids, found abundantly in skins and seed of grape wine, nuts, peanuts, etc. In the investigation of the neuroprotective properties of resveratrol found that Resveratrol has neuroprotective features both in vitro and in vivo in models of Alzheimer's disease (AD), but it has proved to be beneficial also in ischemic stroke, Parkinson's disease, Huntington's disease, and epilepsy, according to "Neuroprotective properties of resveratrol in different neurodegenerative disorders" by Albani D, Polito L, Signorini A, Forloni G.(3). Others, in the elucidation of the neuroprotective effect and influence of resveratrol on the extracellular levels of neurotransmitter and neuromodulator during ischemia/reperfusion in rats, found that chronic treatment with resveratrol remarkably reduced the release of excitatory neurotransmitter glutamate, aspartate and neuromodulator d-Serine during ischemia and reperfusion; and significantly increased the basal extracellular levels of inhibitory neurotransmitter gamma-amino-n-butyric acid, glycine and taurine. Chronic treatment with resveratrol also ameliorated O-phosphoethanolamine levels and excitotoxic index during ischemia and reperfusio, according to "Neuroprotective effects of resveratrol on ischemic injury mediated by modulating the release of neurotransmitter and neuromodulator in rats" by Li C, Yan Z, Yang J, Chen H, Li H, Jiang Y, Zhang Z(3)

4. Rheumatoid Arthritis (RA)
Resveratrol found abundantly in red wine and the skin and seed of grape is said to have an anti RA effect. In the study of Effects of resveratrol in inflammatory arthritis, showed that according to control group in the resveratrol group, significantly decreased cartilage destruction was determined by H&E staining (p = 0.04). Loss of matrix proteoglycan content in the cartilage was much lower, as determined by safranin O staining (p = 0.03). We also observed marked synovial inflammation after intra-articular injection to control knees, but not in the resveratrol treated group knees (p = 0.01)(4).

5. Polymalagia Arthritis(PMR)
Green tea contains more amount of antioxidants than any drinks or food with the same volume, and is the leaves of Camellia sinensis, undergone minimal oxidation during processing, originated from China. Green tea has been a precious drink in traditional Chinese culture and used exceptional in socialization for more than 4000 thousand years. Because of their health benefits, they have been cultivated for commercial purposes all over the world.
a.  Immune system
a. 1. In the investigation of the immunomodulatory effects of decaffeinated green tea extract in rain bow of the study of "Immunomodulatory effects of decaffeinated green tea (Camellia sinensis) on the immune system of rainbow trout (Oncorhynchus mykiss)" by Sheikhzadeh N, Nofouzi K, Delazar A, Oushani AK.(32), researchers found that showed that decaffeinated green tea in lower doses of administration could be optimum to enhance the immunity of rainbow trout(5).

a.2. In the investigation of Green tea and Arthritis of the study of "Green tea polyphenol epigallocatechin 3-gallate in arthritis" by Ahmed S., researcher indicated that although these findings provide scientific evidence of the anti-rheumatic activity of EGCG, further preclinical studies are warranted before phase clinical trials could be initiated with confidence for patients with joint diseases(6).

6. Cataracts
In the study to evaluate the potential role that FoxO transcription factors play in modulating resveratrol's protective effects against oxidative stress in lens epithelial cells, showed that RES exerts a protective effect against oxidative damage in LEC cultures. The levels of expression of FoxO1A, FoxO3A, and FoxO4 appear to play a central role in determining the pro- or anti-apoptotic effects of RES. This has implications for future studies on oxidative stress-related lenticular disorders such as cataract formation(7).

7. Chronic obstructive pulmonary disease (COPD)
In the study to investigate the effect of dexamethasone versus resveratrol on the release of COPD-related inflammatory mediators (IL-6, IL-8, GM-CSF and MCP-1) and matrix-metalloprotease-9 (MMP-9) from alveolar macrophages exposed to gram-negative bacterial endotoxin (lipopolysaccharide, LPS), found that resveratrol almost completely reduced the release of all cytokines and MMP-9 without significant differences between the cohorts. Our data provide evidence for a corticosteroid resistance of alveolar macrophage-dependent inflammatory responses induced by gram-negative bacteria in COPD and thus question the utility of corticosteroids in COPD therapy. Instead, resveratrol may prove an alternative(8).

8. Chronic fatigue syndrome (CFS)
Resveratrol is a photochemical found abundantly in skin and seeds of grape. In the study of a chronic fatigue murine model by six repeated injections of Brucella abortus antigen to mice, which was manifested as reduced daily running activity and hippocampal atrophy, showed that resveratrol may be effective for improving fatigue symptoms and enlarging the atrophic hippocampus by repressing apoptosis and promoting neurogenesis(9).

10. Autoimmune diseases
Mast cells are immune cells critical in the pathogenesis of allergic, but also inflammatory and autoimmune diseases through release of many pro-inflammatory cytokines such as IL-8 and TNF. Compared the flavonoid quercetin (Que) and cromolyn on cultured human mast cells. Que and cromolyn (100 µM) can effectively inhibit secretion of histamine and PGD(2). Que and cromolyn also inhibit histamine, leukotrienes and PGD(2) from primary human cord blood-derived cultured mast cells (hCBMCs) stimulated by IgE/Anti-IgE. However, Que is more effective than cromolyn in inhibiting IL-8 and TNF release from LAD2 mast cells stimulated by SP. Moreover, Que reduces IL-6 release from hCBMCs in a dose-dependent manner. Que inhibits cytosolic calcium level increase and NF-kappa B activation. Interestingly, Que is effective prophylactically, while cromolyn must be added together with the trigger or it rapidly loses its effect(10). 

11. Candidiasis
In the study to investigate the antifungal action by resveratrol in Candida albicans, which is a human infectious fungi as an agent of candidiasis, showed that A significant accumulation of intracellular trehalose was induced by stress responses to resveratrol action, and a remarkable arrest of cell-cycle processes at the S-phase in C. albicans occured. Therefore, the fungicidal effects of resveratrol demonstrate that this compound is a potential candidate as an antifungal agent in treating infectious diseases by candidal infections(11). 

12. Crohn's disease
in the study to examine the response to resveratrol by cultured smooth muscle cells isolated from colons of untreated Lewis rats, found that resveratrol decreases intestinal smooth muscle cell numbers through its effects on cell cycle arrest and apoptosis and also decreases collagen synthesis by the cells. These effects could be useful in preventing the smooth muscle cell hyperplasia and collagen deposition that characterize stricture formation in Crohn's disease(12).

13. Endometriosis
In the study to investigate the effects of resveratrol on human endometriotic implants in a nude mouse model and to examine its impact on human endometrial stromal (HES) cell invasiveness in vitro, found that resveratrol decreased the number of endometrial implants per mouse by 60% (P < 0.001) and the total volume of lesions per mouse by 80% (P < 0.001). Resveratrol (10-30 μM) also induced a concentration-dependent reduction of invasiveness of HES by up to 78% (P < 0.0001). Resveratrol inhibits development of endometriosis in the nude mouse and reduces invasiveness of HES cells. These observations may aid in the development of novel treatments of endometriosis(13).  

14. Flu (influenza)
In the study of assayed the bioactivity of resveratrol as antiproliferative and antiviral drug in cultured fibroblasts. Studies by other Authors showed that this natural compound inhibits the proliferation of different viruses such as herpes simplex, varicella-zoster and influenza A. Resveratrol can effectively inhibit the synthesis of polyomavirus DNA. A possible interpretation is that, due to the damage caused by resveratrol to the plasma membrane, the transfer of the virus from the endoplasmic reticulum to the nucleus, may be hindered thus inhibiting the production of viral DNA(14). 

15. Hepatitis
Resveratrol (RES), a well-known antioxidant and anti-inflammatory compound is associated of reduced risk of chronic liver diseases, researchers at the Ohio Universities Colleges of Medicine and Pharmacy indicated that enhancement of the dissolution of RES through a nanoparticle engineering process can result in increased hepatoprotective effects mediated by antioxidant and anti-inflammatory activities. Consequently, we suggest that RESN deserves further study, perhaps in prophylaxis of chronic liver diseases(15)

16. Human immunodeficiency virus (HIV)
In the study of Resveratrol is a polyphenolic plant-derived antioxidant abundantly found in certain grapes, roots, berries, peanuts and red wine, indicated that using primary human cardiomyocytes, evaluated the effects of AZT and pre-treatment with resveratrol on mitochondrial ROS generation and the cell death pathways. AZT induced concentration-dependent cell death, involving both caspase-3 and -7 and poly(ADP-ribose) polymerase activation, coupled with increased mitochondrial ROS generation in human cardiomyocytes(16). 

17. Genital herpes
Resveratrol, a phytochemicals found in skin and seed of grape and red wine esveratrol  (i) suppresses HSV induced activation of NF-kappaB within the nucleus and (ii) impairs expression of essential immediate-early, early and late HSV genes and synthesis of viral DNA(17). 

18. Liver disease
Resveratrol is a plant-derived polyphenol that has a potential as a food source to extend lifespan and healthspan in model organism. In the study of the effect of resveratrol on mTOR signalingshowed that
resveratrol is an inhibitor of global protein synthesis, and that this effect is mediated through modulation of mTOR-dependent and independent signaling(18) 

19. Multiple Sclerosis
In the study to investigate whether polyphenols modulate the expression and activity of the enzymes gelatinases A (MMP-2) and B (MMP-9), involved in the pathogenesis of multiple sclerosis (MS),
indicate that the flavonoids and non-flavonoids (flavonoids quercetin (QRC) and cathechins [green tea extract (GTE)] and the non-flavonoids resveratrol (RSV) and tyrosol/hydroxytyrosol (Oliplus)) tested exert their inhibitory effect on MMPs, displaying different mechanisms of action, possibly related to their structure. Therefore, their combined use may represent a powerful tool for the down-regulation of MMPs in the course of MS(19). 

20. Osteoporosis
In the study to investigate the molecular mechanism of how resveratrol can modulate the lineage commitment of human mesenchymal stem cells to osteogenesis other than adipogenesis, showed that
resveratrol promoted spontaneous osteogenesis but prevented adipogenesis in human embryonic stem cell-derived mesenchymal progenitors. Resveratrol upregulated the expression of osteo-lineage genes RUNX2 and osteocalcin while suppressing adipo-lineage genes PPARγ2 and LEPTIN in adipogenic medium. Furthermore,  the osteogenic effect of resveratrol was mediated mainly through SIRT1/FOXO3A with a smaller contribution from the estrogenic pathway(20). 

21. Parkinson's disease
In the study to investigate the neuroprotective effects of resveratrol on 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease in rats. 6-OHDA-induced Parkinson's disease rat model involves chronic inflammation, mitochondrial dysfunction, and oxidative stress, and the loss of the dopaminergic neurons in the substantia nigra is the predominant lesion, found that resveratrol treatment also significantly decreased the levels of COX-2 and TNF-alpha mRNA in the substantia nigra as detected by real-time RT-PCR. COX-2 protein expression in the substantia nigra was also decreased as evidenced by Western blotting. These results demonstrate that resveratrol exerts a neuroprotective effect on 6-OHDA-induced Parkinson's disease rat model, and this protection is related to the reduced inflammatory reaction(21).

22. Pelvic inflammatory disease
 Anti-inflammatory effects of resveratrol and its potential use in therapy of immune-mediated diseases  review provides an up-to-date discussion on recent advances regarding anti-inflammatory effects of resveratrol, mechanisms of action, and its potential for therapeutic use(22). 

23. Thyroid disorders
In the study of resveratrol, the main ingredient found in skin and seed of grape and its impact on aging and thyroid function, showed that resveratrol is believed to regulate several biological processes, mainly metabolism and aging, by modulating the mammalian silent information regulator 1 (SIRT1) of the sirtuin family. Resveratrol may arrest, among various tumors, cell growth in both papillary and follicular thyroid cancer by activation of the mitogen-activated protein kinase (MAPK) signal transduction pathway as well as increase of p53 and its phosphorylation. Finally, resveratrol also influences thyroid function by enhancing iodide trapping and, by increasing TSH secretion via activation of sirtuins and the phosphatidylinositol- 4-phosphate 5 kinase γ (PIP5Kγ) pathway, positively affects metabolism(23)

24. Etc. 

D. Quoted From Foods to prevent and treat cancers
1.  Brain and Spinal Cord Cancer
Resveratrol is a type of natural phenol found abundantly in Grapes, red wine, berries and peanuts of the group of Stilbenoids, produced naturally by many plants when under attack by bacteria or fungi. It has been studied by many researchers for it health benefits in treating chronic diaereses, including cancer, diabetes, heart disease, etc. Resveratrol is known to have antioxidant, anti-inflammatory and antiproliferative effects on a variety of cancer cells in vitro and in various animal models. However, the effect(s) of resveratrol in vivo on humans are still controversial. This study discusses current knowledge with regard to the effects of resveratrol in relation to its potential as a chemopreventive and/or chemotherapeutic molecule against human gliomas(1).

2. Esophageal cancer
Resveratrol (3,5,4'-trihydroxy-trans-stilbene), a polyphenol found in the skin of the grape and red wine, has been found to have chemopreventitive effects in some carcinogenic models. In the observation to evaluate the effects of resveratrol on the transition from reflux esophagitis to Barrett's metaplasia to dysplasia to esophageal adenocarcinoma in an established rat model. Male Sprague-Dawley rats underwent esophagoduodenal anastomosis as per institutional approved protocol, showed that morphological characteristics consistent with decreased esophagitis and incidences of metaplasia and esophageal adenocarcinoma were seen on histopathology in the resveratrol group. Resveratrol resulted in a small diminution of the carcinogenic effects and progression to metaplasia, and further human studies are designed to explore the potential anticarcinogenic mechanism(2).

3. Cervical Cancer
Resveratrol, a polyphenol found a abundantly in  skins of grapes and red wine has been shown to significantly alter the cellular physiology of tumor cells, as well as block the process of initiation and progression, some studies found that tumor cells may exhibit changes in the cellular response to IR following exposure to resveratrol, a naturally occurring compound that inhibits cyclooxygenase-1 (COX-1) activity. Thus, clonogenic cell survival assays were performed using irradiated HeLa and SiHa cells pretreated with resveratrol prior to IR exposure, and resulted in enhanced tumor cell killing by IR in a dose-dependent manner(3).

4. Breast cancer
In study of red wine intake and its beneficial health effects on the proliferation of hormone-dependent breast cancer cells found that the estrogenic activity of PIC(piceatannol) and MYR(myricetin) might be considered at least as a potential factor in the association of red wine intake and breast tumors, particularly in postmenopausal women, according to "The red wine phenolics piceatannol and myricetin act as agonists for estrogen receptor alpha in human breast cancer cells" by Maggiolini M, Recchia AG, Bonofiglio D, Catalano S, Vivacqua A, Carpino A, Rago V, Rossi R, Andò S.(4)

5. Hodgkin's lymphoma
In the study to explore the effect of resveratrol on B-cell leukemia/lymphoma-2 (Bcl-2) and vascular endothelial growth factor (VEGF) expression in rats with oxygen-induced retinopathy of prematurity (ROP), found that Resveratrol can significantly inhibit expression of Bcl-2 and VEGF in the retina of neonatal rats with oxygen-induced ROP. It may provide a protective effect on retinal neovascular diseases, including ROP(5).

6. Renal cell carcinoma (Kidney cancer/renal cells)
Resveratrol (Res) is a phytochemical in the class of Stilbenoids, found abundantly in skins and seed of grape wine, nuts, peanuts, etc. has potential to be used in treating kidney cancer. In the study to investigated the effects of Res on the expression of the vascular endothelial growth factor (VEGF) gene and on cell proliferation in human renal cancer (786-0) cells, suggested that Res inhibited the expression of the VEGF gene, and its inhibitory effect increased according to the concentration and treatment time. These results indicate that Res significantly inhibits the proliferation of 786-0 cells and exerts an antitumor effect by suppressing the expression of the VEGF gene(6).

7. Ovarian cancer
Myricetin is a flavonol, belong to the flavonoid in Flavonoids (polyphenols), found in many grapes, berries, etc.. In the research of inverse associations with certain flavonoids or flavonoid subclasses (myricetin, kaempferol, quercetin, luteolin, and apigenin) and ovarian cancer risk, found that In analyses of each individual flavonoid, only intake of apigenin was associated with a borderline significant decrease in risk (RR, highest vs. lowest quintile = 0.79, 95% CI = 0.59-1.06; p-trend = 0.26), and this association was significant after adjustment for intake of the other 4 individual flavonoids (comparable RR = 0.72, 95% CI = 0.53-0.98; p-trend = 0.09), according to "Flavonoid intake and ovarian cancer risk in a population-based case-control study" by Gates MA, Vitonis AF, Tworoger SS, Rosner B, Titus-Ernstoff L, Hankinson SE, Cramer DW.(7)

8. Skin cancer
in the study to evaluate the chemopreventive effects of resveratrol against UVB radiation-mediated skin tumorigenesis in the SKH-1 hairless mouse model, suggests that resveratrol enhanced apoptosis in UVB-exposure-mediated skin tumors. Our study, for the first time, demonstrated that 1) resveratrol imparts strong chemopreventive effects against UVB exposure-mediated skin carcinogenesis (relevant to human skin cancers), and 2) the chemopreventive effects of resveratrol may, at least in part, be mediated via modulations in Survivin and other associated events. On the basis of our work, it is conceivable to design resveratrol-containing emollient or patch, as well as sunscreen and skin-care products for prevention of skin cancer and other conditions, which are believed to be caused by UV radiation(8).

9. Prostate cancers
Myricetin, a flavonol, belong to the flavonoid in Flavonoids (polyphenols), found in many grapes, berries, fruits, etc has been used as antioxidant to lower cholesterol, treat certain types of cancer, etc.
In the selection of several potential uPA inhibitors (antipain, leupeptin, folic acid, rosmarinic acid, lavendustin A, fisetin, myricetin, tolfenamic acid) and examination of theirs effects in prostate cancer found that a proper diet rich in uPA-inhibiting nutraceuticals might support the prevention of prostrate cancer and be a supportive tool in prostate cancer treatment, according to "Nutraceutical inhibitors of urokinase: potential applications in prostate cancer prevention and treatment" by Jankun J, Selman SH, Aniola J, Skrzypczak-Jankun E.(9)

10. Pancreatic cancer
Myricetin, a flavonol, belong to the flavonoid in Flavonoids (polyphenols), found in many grapes, berries, etc. has been used as antioxidant to lower cholesterol, treat certain types of cancer, etc. In the observation of the flavonoid myricetin and its effect on metastatic pancreatic cancer cell lines, found that myricetin resulted in tumor regression and decreased metastatic spread. Importantly, myricetin was non-toxic, both in vitro and in vivo, underscoring its use as a therapeutic agent against pancreatic cancer, according to the study of "Myricetin induces pancreatic cancer cell death via the induction of apoptosis and inhibition of the phosphatidylinositol 3-kinase (PI3K) signaling pathway" by Phillips PA, Sangwan V, Borja-Cacho D, Dudeja V, Vickers SM, Saluja AK.(10)

11. Multiple myeloma (Myeloma)
In the study to investigate the effect of Resveratrol trans-3, 4', 5,-trihydroxystilbene, insuppressing the multiple myeloma (MM), found that Resveratrol activated IRE1α as evidenced by XBP1 messenger RNA splicing and phosphorylation of both IRE1α and its downstream kinase c-Jun N-terminal kinase in MM cells. These responses were associated with resveratrol-induced cytotoxicity of MM cells. Resveratrol selectively suppressed the transcriptional activity of XBP1s while it stimulated gene expression of the molecules that are regulated by the non-IRE1/XBP1 axis of the ER stress response. Luciferase assays indicated that resveratrol suppressed the transcriptional activity of XBP1s through sirtuin 1, a downstream molecular target of resveratrol. Chromatin immunoprecipitation studies revealed that resveratrol decreased the DNA binding capacity of XBP1 and increased the enrichment of sirtuin 1 at the XBP1 binding region in the XBP1 promoter(11).

12. Oral cancer
Resveratrol and quercetin are polyphenols which have been found in abundantly in significant amounts in green vegetables, citrus fruits and red grape wines. Quercetin exhibited a biphasic effect, stimulation at 1 and 10 microM, and minimal inhibition at 100 microM in cell growth and DNA synthesis. Combining 50 microM of resveratrol with 10, 25 and 50 microM of quercetin resulted in a gradual and significant increase in the inhibitory effect of quercetin on cell growth and DNA synthesis(12).

13. Melanoma skin cancer
In the examined the effect of grape seed proanthocyanidins (GSPs) on melanoma cancer cell migration and the molecular mechanisms underlying these effects using highly metastasis-specific human melanoma cell lines, A375 and Hs294t, indicated that GSPs have the ability to inhibit melanoma cell invasion/migration by targeting the endogenous expression of COX-2 and reversing the process of epithelial-to-mesenchymal transition(13).

14. Non-Hodgkin's Lymphoma
Resveratrol is a phytochemical in the class of Stilbenoids, found abundantly in skins and seed of grape wine, etc. Resveratrol (trans-3,4,5-trihydroxystilbene) has received attention for its potential chemopreventive and antitumor effects in experimental systems. Dr. Jazirehi AR and Dr. Bonavida B. at the  University of California at Los Angeles, in the study investigated whether resveratrol can sensitize NHL and MM cell lines to paclitaxel-mediated apoptosis and to delineate the underlying molecular mechanism of sensitization. Both resveratrol and paclitaxel negatively modulated tumor cell growth by arresting the cells at the G(2)-M phase of the cell cycle, suggested that  Resveratrol selectively down-regulated the expression of antiapoptotic proteins Bcl-x(L) and myeloid cell differentiation factor-1 (Mcl-1) and up-regulated the expression of proapoptotic proteins Bax and apoptosis protease activating factor-1 (Apaf-1)(14).

15. Lung cancer
In the examination of study the mechanism of myricetin and its effect on the HepG-2 cell line found that Myricetin significantly inhibits the proliferation and induces the apoptosis of HepG-2 in a dose-dependent manner, which is accompanied with G2/M and S phase arrest. In addition, myricetin also increases the activation of caspase 3,9 and results in a depolarization and delta psi m collapse in a dose-dependent manner, according to "[Studies on mechanism of myricetin-induced apoptosis in human hepatocellular carcinoma HepG-2 cells].[Article in Chinese]" by Zhang X, Ling Y, Yu H, Ji Y.(15)

16. Larynx Cancer or Laryngeal Cancer
Flavonoids  found abundantly in wine have exerted  the potential effect in preventing and treating Laryngeal Cancer. Dr. Garavello W and the research team at the Istituto di Ricerche Farmacologiche Mario Negri, indicated that Significant inverse relations were found for the highest versus the lowest quintile of intake for flavan-3-ols (OR = 0.64), flavanones (OR = 0.60), flavonols (OR = 0.32) and total flavonoids (OR = 0.60), although the overall trends in risk were significant only for flavanones and flavonols. No consistent associations were observed for isoflavones, anthocyanidins and flavones. The estimates did not differ substantially across strata of alcohol drinking, tobacco smoking, body mass index and education, and tended to persist even after controlling for vegetable and fruit intake(16).

17. Etc.

Side Effects
1. Overdose may cause headache, itchy scalp, dizziness, and nausea, abdominal pain etc.
2. Do not take the herbs if you have high blood pressure
3. Grape seed extract may interact with other medication, such blood thinner, NSAID painkiller, etc.
4. Do not take the herb in children or if you are pregnant without approval of the related field specialist.
5. etc.

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A. Quoted From The World Most Healthy herbs


B. Quoted From Phytochemicals in Foods
B.1. Resveratrol  

B.2. Pterostilbene

B.3. Piceatannol
C. Quoted Foods to prevent and treat diseases

D. Quoted Foods to prevent and treat cancers 

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