Red grape polyphenol, resveratrol: a multifaceted therapeutic powerhouse under review

In a recent review published in Nutrients, researchers reviewed existing data on the therapeutic potential of resveratrol, a red grape polyphenol.

Study: The Pharmacological Properties of Red Grape Polyphenol Resveratrol: Clinical Trials and Obstacles in Drug Development. Image Credit: Danijela Maksimovic/Shutterstock.comStudy: The Pharmacological Properties of Red Grape Polyphenol Resveratrol: Clinical Trials and Obstacles in Drug Development. Image Credit: Danijela Maksimovic/


Resveratrol, an antioxidant-rich medication, has been shown to have anticancer, anti-inflammatory, cardioprotective, and neurological effects.

Despite its potential for cancer therapy and prevention, obstacles such as low solubility, bioavailability, and side effects impede drug development. The potential of resveratrol remains a viable path for therapeutic development.

About the review

In the present review, researchers described the sources, metabolism, health benefits, properties, and mechanism of action of resveratrol.

Resveratrol- Natural sources, metabolism, and health benefits

Grapes and grape products, chocolate and cocoa items, pistachios, red wine, blueberries, raspberries, huckleberries, and peanuts all contain resveratrol.

Resveratrol-3' glucoside is released by grape phytochemicals into the stomach and duodenum, where it undergoes phase I and II metabolisms to become resveratrol-4'-glucuronide, which is taken up by cells via systemic circulation and excreted in feces as resveratrol-4' sulfate and in urine as resveratrol-3' sulfate.

Resveratrol is anticancer, analgesic, anti-inflammatory, anti-diabetic, neuroprotective, antiviral, anti-obesity, cardioprotective, antioxidant, anti-aging, and nephroprotective. Resveratrol can decrease cardiac muscle hypertrophy, control cellular differentiation, and improve blood circulation.

The drug also aids in treating depression, preventing brain damage, and improving cognition. Further, resveratrol can help with intestinal swelling, digestion, and constipation. In adipose tissues, it can affect fat cell development and mitochondrial synthesis.

In addition, the drug can reduce the risk of osteoporosis and arthritis, increase bone regeneration, and improve insulin responsiveness in muscles. Resveratrol can decrease oxidative stress and drug toxicity in the kidneys, lower asthma symptoms, and suppress lung tumor formation pathways.

It can also minimize the creation of scar tissue and the risk of diabetes. Resveratrol can also help with lipid storage, cholesterol reduction, and protection against hepatitis C, fibrosis, and cancer. It can also lengthen ovarian life, decrease age-related infertility, and improve estrogen metabolism.

Pharmacological properties and mechanism of action of resveratrol

Resveratrol protects the heart by lowering reactive oxygen species (ROS), preventing inflammation, inhibiting low-density lipoprotein (LDL) oxidation, increasing lipoprotein lipase, high-density lipoprotein (HDL), and vascular endothelial growth factor (VEGF) levels, and improving Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) scores.  

Resveratrol has anti-diabetic effects via lowering glucose bioavailability and boosting the levels of 5′-AMP-activated protein kinase (AMPK), sirtuin type 1 (SIRT1), and peroxisome proliferator-activated receptor-coactivator one alpha (PGC-1α).

The red grape polyphenol stimulates the immune system by raising the levels of cytokines, matrix metalloproteinases (MMPs), vascular cell adhesion molecule (VCAM), intercellular adhesion molecule (ICAM), VEGF, and cyclooxygenase 2 (COX2).

The drug can reduce obesity by increasing AMPK and PGC-1α levels, in addition to decreasing ROS-induced inflammation.

Furthermore, resveratrol protects the brain by boosting the levels of nuclear factor erythroid 2-related factor 2 (Nrf2), insulin-like growth factor 1 (IGF-1), COX2, and insulin-like growth factor-binding protein 3 (IGFBP-3).

Resveratrol inhibits cancer growth by preventing cell proliferation and deoxyribonucleic acid (DNA) damage, increasing nuclear factor-kB (NF-B), wingless-related integration site (Wnt), tumor necrosis factor-alpha (TNF-), RAS association domain family isoform A (RASSF-), and B-cell lymphoma 2 (Bcl-2) levels, and decreasing Bcl-2-associated X protein (Bax) and caspase-3 levels.

Clinical trials and recent advances related to resveratrol

In clinical trials, resveratrol at doses ranging from 20 to 600 mg daily for three to 84 days raised serological non-HDL cholesterol (non-HDL-C) and total cholesterol (TC) levels, reduced the weight of cholesterol and lipid in atherosclerosis-associated plaques and lowered serological TC/HDL-C  levels in individuals with coronary heart disease. 

Sixty to 300mg daily of resveratrol promoted flow-mediated dilatation (FMD) among hypertensive women and individuals with higher levels of LDL-C and lowered diastolic-type blood pressure.

Resveratrol in 250 mg daily doses for 90 days reduced glycated hemoglobin (HbA1c), systolic blood pressure, total protein, and TC levels in type 2 diabetic patients. Even 5.0 mg two times a day for 30 days of the drug decreased insulin and glucose levels and delayed post-meal glucose increases.  

Resveratrol increased the prostate-specific antigen doubling time (PSADT), decreased androstenedione and dehydroepiandrosterone (DHEAS) levels, increased caspase-3 levels, and blocked RASSF-1 methylation in cancer patients.

Resveratrol at doses ranging from 5.0 to 1,000 mg per day for eight to 120 days was safe and well-tolerated by individuals, with reported adverse effects including nausea, weight loss, and diarrhea.

Recent advances in increasing resveratrol's biological activity include self-emulsification-based resveratrol medication delivery systems, resveratrol micellar solubilization, resveratrol-filled nanoparticles delivered using oat-shellac proteins, resveratrol nanoencapsulation in casein, trans-resveratrol nanocrystals, and RES-BSANP (RES-BSANP).

The nanoformulations enhanced absorption, pharmacokinetics, solubility, bioavailability, systemic exposure, targeting, and cytotoxicity while reducing metabolism.


Overall, the review findings highlighted the pharmacological properties and underlying mechanisms of resveratrol, which are associated with hormetic effects, i.e., low doses have beneficial effects, and high doses are toxic.

Further research must validate the findings and facilitate drug development to decrease the global burden of medical conditions such as diabetes, obesity, hypertension, neurodegenerative disorders, and cancer.

Journal reference:
Pooja Toshniwal Paharia

Written by

Pooja Toshniwal Paharia

Pooja Toshniwal Paharia is an oral and maxillofacial physician and radiologist based in Pune, India. Her academic background is in Oral Medicine and Radiology. She has extensive experience in research and evidence-based clinical-radiological diagnosis and management of oral lesions and conditions and associated maxillofacial disorders.


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  1. Nick Christopherson Nick Christopherson United States says:

    if this stuff works so well how come GSK bought it for 720 million dollars...put an extra 300 million into research then just drop it after a year

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
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