RESVERATROL RESEARCH PROJECT

Openlink is currently studying the phenolic components of Resveratrol for their ability to affect RNA synthesis. Resveratrol is a polyphenolic compound found in red grapes. It is one of the most talked about skincare ingredient of today’s times. It was first reported in a Japanese article in 1939 by Michio Takaoka. It rose to prominence due to its reported anti-ageing properties which could be attributed to its free radical scavenging nature. It is also in the limelight for its anti-cancer activity as well. It also maintains the collagen and moisture of the skin to keep it healthy and young. Recent studies have shown that resveratrol has anti-acne capabilities as well. Resvology, a skincare company, claims that their products contain an ester form of resveratrol called resveratryl acetate which can smoothen lines and wrinkles. Resveratrol has been used as one of the ingredient for the treatment of fungal, inflammatory, hypertensive, allergic, and lipid in the traditional Asian medicine Ko-jo-kon (Crowell et al., 2004).
Resveratrol is found mainly in the skin of red grapes and in the roots of Polygonum cuspidatum (Japanese knotweed). Red wine is considered to be the richest source and contains 0.1-14.3 mg/L of resveratrol (Baur and Sinclair, 2006). It can be consumed in daily diet in the form of peanuts, berries, coco, grapes and chocolate. It has been found that resveratrol is present in more than 70 plant species. Many research groups have concluded that the benefits of wine consumption can be attributed to this polyphenolic compound. In France, there are lower incidences of coronary heart diseases even though they consume a diet rich in saturated fat and cholesterol. This has been attributed to the higher red wine intake by the French population. This ironical situation in which the French consume a rich diet and are still protected from its ill effects was first reported by Renaud and Lorgeril in 1992, who called it the ‘French Paradox’ (Ndiaye et al., 2011).
Resveratrol is chemically called 3,5,4’-trihydroxystilbene. It is a polyphenolic compound produced with the help of enzyme stilbene synthase. Like other polyphenols, resveratrol is also produced in plants in response to stress factors like injury, fungal infections or UV irradiation. Resveratrol is present in two structural isomeric forms: cis and trans. The trans isomer is more active biologically than the cis isomer. The reason for the better biological activity of the trans isomer is its nonplanar conformation. The trans form can isomerise to the cis form on exposure to UV light (Baur and Sinclair, 2006). But the effective use of trans resveratrol is limited because of its short biological half life and rapid metabolism and elimination. It also has low water solubility and is extremely photosensitive (Matos et al., 2013).
Resveratrol is known for its beneficial pharmacological properties like anti- aging, antioxidant, analgesic, anti-inflammatory, chemo-preventive, anti-platelet aggregation, anti-atherogenic, immunomodulation, cardioprotective and neuro-protective actions (Isailovic et al., 2013).
• The antioxidant effect of resveratrol is due to its free radical scavenging action. Studies have shown that resveratrol is a stronger antioxidant than catechin, myricetin, kaempferol, etc. The anti-radical activity of this polyphenol is responsible for most of its beneficial actions (Khanduja and Bhardwaj, 2003). The exact mechanism of action is still unclear but various research groups have pointed out the involvement of sirtuin SIRT1 receptors. Resveratrol activates SIRT1 receptors directly or may inactivate phosphodiesterase enzymes (PDEs) leading to a cascade which leads to activation of SIRT1. It has also been hypothesized to scavenge reactive oxygen species (ROS) and reduce facial redness which might have been caused by sun damage or atopic/contact dermatitis(Ferzil et al., 2013).
• Resveratrol’s antimutagenic activity was reported first in a study in 1997 where it was shown to induce phase II drug-metabolizing enzymes (anti-initiation activity), mediate anti-inflammatory effects by inhibiting cyclooxygenase and hydroperoxidase enzymes and prevented cancer progression (Jang et al., 1997).
• The anti-acne effect of resveratrol was tested in a clinical study using a gel containing the drug. None of the patients showed any adverse effect and all were satisfied with the results. The data was supported by histopathological evidence where a 66.7% mean reduction in the average area of microcomedones on the resveratrol-treated sides of the face was observed. Though the exact mechanism could not be deduced but this study opened a new gateway into resveratrol research for skincare (Fabbrocini et al., 2011).

Williams and coworkers have performed the safety studies of resveratrol using high purity trans isomer. The safety studies included skin and eye irritation study, dermal sensitization study, genotoxicity study, subchronic and reproductive toxicity studies, and absorption, metabolism and excretion studies. It was found to be non-irritating to skin and eyes and non-sensitizing as well. Its mutagenic potential was tested using the bacterial reverse mutation assay in Salmonella typhimurium and Escherichia coli, in which it was found to be non mutagenic. This high purity compound was also found to be non genotoxic in an in vivo bone marrow micronucleus test in rats (Williams et al., 2009).
But the question arises about the safety of resveratrol for human use because of the limited clinical studies that have been conducted and thus very limited data is present. Majority of preclinical data of safety and toxicity studies has been carried out using assay procedures. But it is always doubtful to extrapolate assay data to humans because in preclinical assay studies, in vitro tests are carried out with non-physiological metabolites and there are short-term exposures, etc. Hence, there are still a number of questions that need to be answered regarding resveratrol research (Tome-Carneiro et al., 2013).
But the benefits of resveratrol are unquestionable and it indeed is a very useful skin care product. Its long term effect studies are lacking because it is a relatively new compound and has not been in use for long. But as time passes, newer studies will supplement all the lacking data and bring forward detailed mechanisms and effects of resveratrol. Thanks to Advanced Dermatology and Skinacea for the research funding for this project. Advanced Dermatology and Skinacea are specialists in Botox research Sydney treatment.

References -
Revelations into resveratrol’s mechanism. Nature Medicine, 18, 500-501.

BAUR, J. A. & SINCLAIR, D. A. (2006) Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov, 5, 493-506.

CROWELL, J. A., KORYTKO, P. J., MORRISSEY, R. L., BOOTH, T. D. & LEVINE, B. S. (2004) Resveratrol-associated renal toxicity. Toxicol Sci, 82, 614-9.

FABBROCINI, G., STAIBANO, S., DE ROSA, G., BATTIMIELLO, V., FARDELLA, N., ILARDI, G., LA ROTONDA, M. I., LONGOBARDI, A., MAZZELLA, M., SIANO, M., PASTORE, F., DE VITA, V., VECCHIONE, M. L. & AYALA, F. (2011) Resveratrol-containing gel for the treatment of acne vulgaris: a single-blind, vehicle-controlled, pilot study. Am J Clin Dermatol, 12, 133-41.
FERZIL, G., PATEL, M., PHRSAI, N. & BRODY, N. (2013) Reduction of facial redness with resveratrol added to topical product containing green tea polyphenols and caffeine. J Drugs Dermatol, 12, 770-4.

ISAILOVIC, B. D., KOSTIC, I. T., ZVONAR, A., DORDEVIC, V. B., GASPERLIN, M., NEDOVIC, V. A. & BUGARSKI, B. M. (2013) Resveratrol loaded liposomes produced by different techniques. Innovative Food Science & Emerging Technologies, 19, 181-189.

JANG, M., CAI, L., UDEANI, G. O., SLOWING, K. V., THOMAS, C. F., BEECHER, C. W., FONG, H. H., FARNSWORTH, N. R., KINGHORN, A. D., MEHTA, R. G., MOON, R. C. & PEZZUTO, J. M. (1997) Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science, 275, 218-20.

KHANDUJA, K. L. & BHARDWAJ, A. (2003) Stable free radical scavenging and antiperoxidative properties of resveratrol compared in vitro with some other bioflavonoids. Indian J Biochem Biophys, 40, 416-22.

MATOS, M., GUTIERREZ, G., COCA, J. & PAZOS, C. (2013) Preparation of water-in-oil-in-water (W1/O/W2) double emulsions containing trans-resveratrol. Colloids and Surfaces A: Physicochemical and Engineering Aspects.

NDIAYE, M., PHILIPPE, C., MUKHTAR, H. & AHMAD, N. (2011) The grape antioxidant resveratrol for skin disorders: promise, prospects, and challenges. Arch Biochem Biophys, 508, 164-70.

TOME-CARNEIRO, J., LARROSA, M., GONZALEZ-SARRIAS, A., TOMAS-BARBERAN, F. A., GARCIA-CONESA, M. T. & ESPIN, J. C. (2013) Resveratrol and clinical trials: the crossroad from in vitro studies to human evidence. Curr Pharm Des, 19, 6064-93.

WILLIAMS, L. D., BURDOCK, G. A., EDWARDS, J. A., BECK, M. & BAUSCH, J. (2009) Safety studies conducted on high-purity trans-resveratrol in experimental animals. Food Chem Toxicol, 47, 2170-82.