Resveratrol has also shown promise as part of combination therapy, particularly in breast cancer [62]. E. coli and Staphylococcus aureus culture supplemented with resveratrol and treated with antimicrobials reduced ROS concentrations to sublethal levels, that are mutagenic, while the absence of resveratrol allows ROS to high enough to kill mutagenized cells. In addition, resveratrol beneficial effects are also present when adopted as a conventional treatment support to cancer, using chemotherapy and radiotherapy [70,71,72]. Globally, many in vitro and animal-based studies have demonstrated such preventive anticancer activity in colon, cervical, prostate, breast and lungs [50,64,65,66,67,68,69]. Baron S., Bedarida T., Cottart C.H., Vibert F., Vessieres E., Ayer A., Henrion D., Hommeril B., Paul J.L., Renault G., et al. Do resveratrol supplements really deliver on those promises? and transmitted securely. In fact, since copper ions are known to be found in a nucleus bound to guanine bases in chromatin, the mobilization of such endogenous copper by resveratrol result in pro-oxidant DNA cleavage at the site. Licensee MDPI, Basel, Switzerland. Pearson K.J., Baur J.A., Lewis K.N., Peshkin L., Price N.L., Labinskyy N., Swindell W.R., Kamara D., Minor R.K., Perez E., et al. The predominant clinical signs of toxicity at 3000 mg/kg b.w./day dose group were dehydration, piloerection, and red material in cage/urine, body weight gain reduction, hyperalbuminemia, anemia (due to renal injury, which reduced erythropoietin synthesis), white blood cell counts increase due to renal pelvic inflammation. Li M., Kildegaard K.R., Chen Y., Rodriguez A., Borodina I., Nielsen J. This result was confirmed in vivo where resveratrol inhibits TNF- production and NF-B activation, decreases neutrophil infiltration in the intestinal mucosa, and represses intestinal tumorigenesis by regulating anti-inflammatory miRNA [97,98]. Resveratrol rapidly activate mitogen-activated protein kinase (MAPK) in a MEK-1, Src, matrix metalloproteinase, and epidermal growth factor receptor in a dependent manner. Resveratrol plays dual roles in pancreatic cancer cells. Endocytosis of resveratrol via lipid rafts and activation of downstream signaling pathways in cancer cells. Aside from drug metabolizing enzymes, it is now greatly acknowledged that transport function modifications are involved in these resveratrol-drug interactions. Resveratrol molecules are synthesized from phenylalanine pathway through multiple enzymatic reactions. On the other hand, it is also speculated that higher resveratrol doses compete with other polyphenols for transporters, reducing both their uptake and potential synergistic effects. Resveratrol was also able to affect cells with changes in cell morphology and DNA contents [105]. Li L., Qiu R.L., Lin Y., Cai Y., Bian Y., Fan Y., Gao X.J. Zhang F., Liu J., Shi J.S. 812, Yaounde-Cameroon, 8Faculty of Medicine, University of Porto, Alameda Prof. Hernni Monteiro, Porto 4200-319, Portugal, 9Institute for Research and Innovation in Health (i3S), University of Porto, Porto 4200-135, Portugal, 10Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran 11369, Iran, 11Department of Chemistry, Richardson College for the Environmental Science Complex, The University of Winnipeg, Winnipeg, MB R3B 2G3, Canada. UID/BIM/04293/2013 and NORTE2020Programa Operacional Regional do Norte (NORTE-01-0145-FEDER-000012). Contrarily, at physiological concentrations, resveratrol induces vasodilation, and consequently decreases hypertension and cardiovascular diseases risk [79]. Till now, small sample size and high dosage levels were used to conduct most of clinical trials to assess resveratrol significance in chronic diseases [84]. Besides, in absence of estrogen (E2), resveratrol exerts mixed estrogen agonist/antagonist activities in some mammary cancer cell lines, but in the presence of E2, resveratrol acts as an anti-estrogen [134]. In plants, resveratrol acts as a phytoalexin that is synthesized in response to mechanical injury, UV irradiation and fungal attacks. The .gov means its official. Robb E.L., Page M.M., Wiens B.E., Stuart J.A. Valentovic M.A. Numerous studies have demonstrated that resveratrol possesses antitumor action and is a likely candidate for treatment and prevention several types of cancer [31,48]. If you take any medicines or other supplements regularly, talk to your health care provider before you start using resveratrol supplements. Previous studies showed that hydroxyl group in 4 position is not the sole determinant for antioxidant activity, but also the 3- and 5-OH groups [40,41]. The use of natural products is prevalent among patients who are taking conventional medicines, leading to a higher risk of natural product-drug interactions. demonstrated that resveratrol significantly suppressed the TLR-4/MyD88/NF-B signaling pathway in lysophosphatidylcholine-induced damage and inflammation that might be useful for treatment of arteriosclerosis [99]. Therefore, modification of resveratrol structure has received special attention from researchers and many resveratrol derivatives have been synthesized such as methoxylated, hydroxylated and halogenated derivatives, all of them exhibiting favorable therapeutic potential [3,16,17]. Therefore, caution should be taken when using supplemental resveratrol doses for health benefits, such as chemoprevention. Kalantari H., Das Dipak K. Physiological effects of resveratrol. official website and that any information you provide is encrypted As of today, 92 new resveratrol compounds, including 39 dimers, 23 trimers, 13 tetramers, 6 resveratrol monomers, 6 hexamers, 4 pentamers, and 1 octamer have been reported from the Dipterocarpaceae, Paeoniaceae, Vitaceae, Leguminosae, Gnetaceae, Cyperaceae, Polygonaceae Gramineae, and Poaceae families [9]. The anticancer properties of resveratrol have been confirmed by many in vitro and in vivo studies, which show that resveratrol is able to inhibit all carcinogenesis stages (e.g., initiation, promotion and progression) [49,50,51]. Moreover, depending on enzymatic reactions conditions, resveratrol can be (auto-)oxidized to generate semiquinones and relatively stable 4-phenoxyl radical, finally leading to ROS production [118,119]. Japanese Knotweed contains high concentrations of trans-resveratrol, the active form of the compound. Evaluation of resveratrol oxidation. Resveratrol decreases cholinergic neurotransmission, brain-derived neurotrophic factor expression, and oxidative stress, promotes -amyloid peptides clearance and anti-amyloidogenic cleavage of APP, and reduces neuronal apoptosis [88]. Received 2018 Aug 14; Accepted 2018 Sep 7. Thus, a shift towards H2O2 favors apoptosis, whereas inclination towards O2- obstructs apoptosis. Bhat K.P.L., Lantvit D., Christov K., Mehta R.G., Moon R.C., Pezzuto J.M. Akinwumi B.C., Bordun K.M., Anderson H.D. Resveratrol may interact with several medications. [117] found that neither cytotoxic or cytostatic activities nor cytoprotective and antioxidant activities in cultured (C6 glioma) cells are indicative of a structureactivity relationship stressing the need to explore mechanisms at molecular level. Cheynier V., Sarni-Manchado P., Quideau S. Park S., Lim J., Kim J.R., Cho S. Inhibitory effects of resveratrol on hepatitis B virus X protein-induced hepatocellular carcinoma. Careers. Resveratrol chemical structure (cis and trans forms). It could cause a reaction in those who are allergic to grapes or wine. One of the most fascinating resveratrol aspects for its future development as a promising drug is that, it does not appear to have debilitating or toxic side effects. But most experts and organizations like the American Heart Association still suggest limiting alcoholic drinks to one per day for women and two for men. Effects of exercise training and resveratrol on vascular health in aging. Cardioprotective effect of resveratrol, a natural antioxidant derived from grapes. Burns J., Yokota T., Ashihara H., Lean M.E.J., Crozier A. Otherwise, at doses of 2.5 g or more per day, side effects may occurs, like nausea, vomiting, diarrhea and liver dysfunction in patients with non-alcoholic fatty liver disease [140]. Plauth A., Geikowski A., Cichon S., Wowro S.J., Liedgens L., Rousseau M., Weidner C., Fuhr L., Kliem M., Jenkins G., et al. Zhao X., Tong W., Song X., Jia R., Li L., Zou Y., He C., Liang X., Lv C., Jing B., et al. Nonetheless, resveratrol application is still being a major challenge for pharmaceutical industry, due to its poor solubility and bioavailability, as well as adverse effects. In some cell types, resveratrol acted as a super agonist, whereas in other ones, it produced an equal to or lesser activation than that of estradiol, and as an antagonist at higher concentrations. From another point of view, reactive oxygen species (ROS), superoxide, peroxide, and hydroxyl radicals are thought to contribute to the rapid bactericidal activity of diverse antimicrobial agents. Resveratrol is widely known for its renowned beneficial biological effects, namely involving its chemopreventive and antioxidant properties. This would result in necrosis, renal tubules obstruction and thus tubules dilation behind obstructed region. Presumably, high resveratrol intakes in the form of supplements could enhance both bruising and bleeding risk when taken with anticoagulant drugs, antiplatelet drugs and even non-steroidal anti-inflammatory drugs (NSAIDs). Additionally, resveratrol consumption at modest doses result in a life span increase in 1-year old mice. Stivala L.A., Savio M., Carafoli F., Perucca P., Bianchi L., Maga G., Forti L., Pagnoni U.M., Albini A., Prosperi E., et al. Dvorakova M., Landa P. Anti-inflammatory activity of natural stilbenoids: A review. Mndez-Vilas A. In this sense, this review summarized current data on resveratrol pharmacological effects. Most resveratrol capsules sold in the U.S. contain extracts from an Asian plant called Polygonum cuspidatum. ztrk E., Arslan A.K.K., Yerer M.B., Bishayee A. Resveratrol and diabetes: A critical review of clinical studies. Zykova T.A., Zhu F., Zhai X., Ma W.Y., Ermakova S.P., Lee K.W., Bode A.M., Dong Z. Resveratrol directly targets COX-2 to inhibit carcinogenesis. Yang et al. For instance, resveratrol have demonstrated apoptotic and anti-proliferative effects on human cervical carcinoma by inducing cell shrinkage in HeLa cells and apoptosis through the activation of caspase-3 and -9, upregulation of the expression of the pro-apoptotic B-cell lymphoma (Bcl)-2-associated X protein and downregulation of the expression of the anti-apoptotic proteins Bcl-2 and Bcl-extra-large in HeLa cells, and increased expression of the p53, a protein that is essential for cell survival and cell cycle progression [54]. Overall, the cardiovascular protective effect of resveratrol have been linked to multiple molecular targets and might be useful to the development of novel therapy for atherosclerosis, metabolic syndrome, ischemia/reperfusion, and heart failure [83]. Evaluation of resveratrol in cancer patients and experimental models. Colin D., Limagne E., Jeanningros S., Jacquel A., Lizard G., Athias A., Gambert P., Hichami A., Latruffe N., Solary E., et al. All authors contributed equally to this work. Pterostilbene anti-MRSA potency was related to bacterial membrane leakage, chaperone protein downregulation, and ribosomal protein upregulation and can be topically applied for treatment of skin MRSA infection bearing it less toxicity to mammalian cells [32].
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