A 1990 study by Yong Nam Han, Shi Yong Ryu, and Byung Hoon Han of the Natural Products Research Institute at Seoul National University in Seoul, Korea conducted at study in which they discovered that the antioxidant activity of resveratrol closely correlates with its ability to inhibit monoamine oxidase-A activity (the activity of molecules with a single amino acid).
Goal of This Study of Resveratrol
Resveratrol, a polyhydroxylstilbene, was reported to inhibit the activity of monoamine oxidase-A. In this study the team from Seoul National University hoped to discover a plausible mechanism by which red wine resveratrol is able to slow the activity level of monoamine oxidase-A.
Researchers first isolated a number of phenolic substances (among them resveratrol) in an attempt to find the most potent inhibitor of monoamine oxidase-A. Components of the study were serotonin and the mitochondrial MAO of rat brain.
Resveratrol as an antioxidant
The study revealed that not only was resveratrol the most powerful antioxidant of the monoamine oxidase-A inhibitors, it completely suppressed MAO-A and became, in the view of the research team, the selective agent for MAO-A inhibiting.
In 1998, O.P. Mgbonyebi, J. Russo, and I.H. Russo of the Breast Cancer Research Laboratory, Fox Chase Cancer Center in Philadelphia conducted studies revolving around the antiproliferative effect of resveratrol on breast epithelial cells.
Introduction to Resveratrol
Resveratrol is a phytoalexin, a natural antibiotic produced by plants. It can be found in many sources in the human diet, such as grapes, peanuts, blue berries, white and red wine, etc.
Basics of This Study of Resveratrol
In the current study, researchers examined synthetic resveratrol supplements to determine the extent of its ability to inhibit the proliferation (explosive reproduction) of malignant breast cancer cells.
Three forms of breast cancer were studied (MCF-7, MCF-10F, and MDA-MB-231). Each was treated with a variety of resveratrol doses (5, 10, 20, and 40 microg/ml).
The team determined that all three lines of breast cancer cells were affected by the resveratrol treatment. Results were dependent on the level of resveratrol dosage and the length of time the cells had been treated with the resveratrol.
Resveratrol was found to have substantial effect as a chemopreventative agent in both hormone responsive and non-responsive forms of breast cancer.
In a 2001 report made by researchers at the Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, and the University of Illinois Cancer Center at the University of Illinois at Chicago K.P.L. Bhat, J.W. Kosmeder II, and J.M. Pezzuto endeavored to summarize the health benefits of the naturally occurring polyphenol resveratrol.
Resveratrol naturally occurs in various plant-derived foods and beverages, such as grapes, peanuts, white and red wine, raw cranberry juice, and so forth. Its health benefits have been observed in the form of cancer prevention and prevention of heart disease among other things.
Antioxidant Benefits of Resveratrol
Resveratrol is a known antioxidant and its ability to promote nitric oxide production is well documented. It has also been shown to increase high-density lipoprotein cholesterol which makes it highly beneficial as a cardiopreventative agent due to the fact that it protects against plaque build up in the arteries.
The estrogenic effect of resveratrol supplements make it a valuable instrument in the fight against breast cancer as it transfects breast cancer cells.
Likely, researchers have only scratched the surface of the many health benefits resveratrol has. Additional studies will allow researchers to not only identify the exact mechanisms by which resveratrol positively impacts so many diseases, but also identify additional health issues that can be helped by resveratrol.
Leading up to this 1999 study, there was a great deal of literature surrounding the health benefits of resveratrol, a polyphenol naturally occurring in many foods and beverages. Its cancer preventative and heart disease preventative characteristics have made red wine resveratrol the focus of many studies. However, Calabrese intended to determine if these health benefits would extend themselves beyond cancer and heart disease and might be an influence on menopause.
Calabrese’s Findings Surrounding Resveratrol
The hypothesis of this study is based on the idea that the structure of resveratrol is so much like that of diethylstilbestrol, a drug prescribed to prevent miscarriages, that it might act as a phytoestrogen in humans.
Calabrese’s team conducted a population study, read literature on resveratrol’s effects on female reproduction, osteoporosis, and cancer, and they conducted various trials of their own.
Their findings concluded that moderate wine consumption appeared to act as a phytoestrogen, a compound in plants that simulates estrogen in humans. Resveratrol doses boosted the physiological reactions that typically accompany estrogen increases.
This activity could effectively moderate the effects and symptoms of menopause in women.
A 2001 study by K. Igura, T. Ohta, Y. Kuroda, and K. Kaji of the Laboratory of Cell and Molecular Biology of Aging, Graduate School of Nutritional and Environmental Sciences at the University of Shizuoka, Yada in Shizuoka, Japan analyzed the effects resveratrol had on the creation of blood vessels in tumors.
Intent of the Study
Both resveratrol and quercetin were studied in varying doses on bovine aorta endothelial (BAE) cells.
Effects of Polyphenols on Angiogenesis
Both resveratrol and quercetin inhibited the migration of BAE which, in turn, stalled vascular formation. Resveratrol inhibited cell growth, to a substantial degree at all dosages while quercetin had a weak effect at lower doses.
Overall Conclusions of Resveratrol Study
Resveratrol doses can have a significant effect on vascular growth in tumors. Without blood flow to the tumors, they become oxygen-deprived and inhibiting growth of the tumor cells. In fact, Resveratrol instigates early natural death in tumor cells.
In 2002, researchers from the Johannes Guttenberg University in Mainz, Germany set out to study the effects of resveratrol on Nitric Oxide Synthase (NAS) to determine its value in the fight against heart disease.
Thomas Wallerath, Ph.D., Goran Deckert, Thomas Ternes, Ph.D., Henrik Anderson, Huige Li, MD, Klaus Witte, MD, and Ulrich Forstermann, MD, Ph.D. conducted the study.
Resveratrol mimics estrogen’s vascular protective behavior
Estrogens have been known to increase endothelial nitric oxide synthase (eNOS), thus protecting the walls of the blood vessels. Since red wine resveratrol is similar in structure to estrogen, it can induce this vascular protective behavior.
This study tested the effects of resveratrol on human endothelial cells.
Testing Resveratrol’s Influence on Vascular Cells
The researchers used human umbilical vein to test resveratrol’s effect on endothelial cells. Cells were incubated for 12 to 72 hours with resveratrol or were left untreated (as in the case of the control). The team then monitored things such as eNOS mRNA, phytoestrogens, eNOS activity, etc.
Results: Resveratrol an effective preventative agent for heart and cardiovascular disease
Resveratrol increase the activity of the eNOS promoter. The eNOS mRNA was thus stabilized by the resveratrol keeping the vascular cells healthy. This discovery shows that resveratrol supplements can be used effectively as a preventative agent for heart and cardiovascular diseases by maintaining vascular cell health.
At the School of Life Sciences at Lanzhou University, G.A. Liu and R.L. Zheng conducted research into the ability of polyphenols (groups of chemicals found in plants) to protect healthy cells against diseases like heart disease and cancer at the cellular level.
Seven polyphenols were studied, among them resveratrol.
DNA damage was induced by using hydrogen peroxide on human peripheral blood lymphocytes (PBL) which is known to cause single strand breakage in DNA. The researchers then observed the ability of the seven polyphenols to protect the cells against the damage the hydrogen peroxide was invoking on the cellular DNA.
Resveratrol Provides Significant Cell Protection
Resveratrol, as well as others of the seven tested polyphenols, had a substantial impact on inhibiting cell damage. The impact was dose-dependent as higher doses were more effective in cell protection.
Some of the polyphenols, however, failed to provide any protection. In fact, only three had any effect in protecting the cells against hydrogen peroxide damage (resveratrol, quercetin, and 7.8-dihydroxy-4-methyl coumarin), but these had a big enough impact to convince the researchers that they had discovered a possible mechanism explaining resveratrol’s outstanding track record in protecting against cancer and heart disease.
A year 2000 report coordinated by Jiangang, Zou, Yuanzhu Huang, Qi Chen, Enhui Wei, Keijiang Cao, and Joseph M. Wu investigated the effects of resveratrol on low density proteins (LDL) also known as the “bad cholesterol.” This team of researchers tested resveratrol on LDLs using two different oxidation systems.
LDLs were isolated from the plasma of two groups of volunteers. Half of these volunteers’ LDLs were oxidized using Cu(2)-induced oxidation and the other half were oxidized with an Azo compound. In both cases, resveratrol doses were added at different concentrations. Any modifications to their LDL levels resulting from the resveratrol dosage were then monitored.
Effects of Resveratrol on LDLs
The LDLs that were oxidized using Cu(2) experienced a 70.5% reduction in TBARS (Thiobarbituric Acid). Higher concentrations had a greater effect on reduction of TBARS than lower doses did.
In these samples, relative electrophoretic mobility (REM) was reduced by 42.3% and macrophage (white blood cell) degradation by 65.7%.
Use of the LDLs oxidized by the Azo compound were intended to further validate the findings in the Cu(2) oxidized LDLs.
Conclusions of Resveratrol Study
The results of this study show that red wine esveratrol has a significant impact on the bad cholesterol lipoproteins that cause plaque build up in arteries.
The use of resveratrol interrupted known reactors in LDLs that cause the build up of plaque and eventual heart disease. Thus, resveratrol is a viable prevention mechanism for heart disease.
Research conducted at the Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill by D.L. Evers, X. Wang, S.M. Huong, D.Y. Huang, and E.S. Huang on the effects of resveratrol on cytomegalovirus (a variety of herpes) revealed some startling results.
Testing Resveratrol as a Herpes Treatment
In this 2004 study, for the first time, red wine resveratrol was tested to determine its effect on cytomegalovirus.
To accomplish this the researchers tested an IC50 strain of cytomegalovirus to determine whether resveratrol could arrest cell development in the virus in the same way it arrests cell development in cancers.
Resveratrol prevented the appearance of viral proteins. In doing so, it reduced DNA replication of the cytomegalovirus to undetectable levels. The researchers hypothesize that resveratrol blocked epidermal growth in the cells and ceased the continued development of the cells.
What this means for the general population is that resveratrol supplements are an effective inhibitor in the development of the Herpes virus, which can be found in anywhere from 50% to 85% of the human population by the time they are 40 years of age.
Hai-Bo Zhou, Juan-Juan Chen, Wen-Xia Wang, Jian-Ting Cai, and Qin Du of the Department of Gastroenerology in the Second Hospital of Zhejiang University set out to study the effects of resveratrol on stomach cancer. The 2004 study revealed some critical findings about resveratrol.
The researchers transplanted human stomach cancer into the subcutaneous tissue of nude mice to determine resveratrol’s effect on live candidates.
Three different doses of resveratrol were tested (500 mg/kg, 1000 mg/kg, and 1500 mg/kg). The dose was directly injected beside the tumor in each candidate. Changes in tumor size were then monitored.
Effects of Resveratrol on Stomach Cancer Tumors
In all cases, the resveratrol inhibited cell growth significantly. As the dose increased, the inhibition rate also increased. In fact, at 1500 mg/kg inhibition rate reached nearly 40%.
In addition to the growth inhibiting effect, resveratrol also induced cell apoptosis (natural cell death) in the cancer cells. A marked reduction of tumor size was observed.
Resveratrol slowed cell development in the stomach cancer cells at a rate of up to 40% and initiated apoptosis in the gastric carcinoma cells.