Resveratrol is a natural molecule with enormous therapeutic potential. It  has been of considerable interest to researchers and clinicians because of the many health promoting properties demonstrated  in preclinical studies. 

https://pmc.ncbi.nlm.nih.gov/articles/PMC9414442/

There have been almost 200 studies evaluating resveratrol for many conditions, including cancer, diabetes, metabolic syndrome, and cardiovascular disease. Resveratrol consistently reduces inflammatory markers and improves aspects of a dysregulated metabolism. In conclusion, the increasing weight of clinical evidence suggests resveratrol can benefit human health, but more large, high-quality clinical trials are required before it could be expect to be widely recommended by clinicians.   Most of the research evaluating resveratrol has been at the preclinical level in cellular and animal models. In the lab, resveratrol has been reported to exert cardioprotective, neuroprotective, antitumor, antidiabetic, antibacterial, and anti-ageing effects; common to some of these effects is its ability to modulate glucose metabolism, oxidative stress, cell death, and inflammation. An extensive review of studies regarding resveratrol was done by accessing publications available online across Medline, and clinicaltrials.gov, . 

There have been over 13,000 publications featuring resveratrol (RSV) in the title since 1977 at which time the research by Jang et al.  documented its potential cancer preventive effects [1].https://pmc.ncbi.nlm.nih.gov/articles/PMC10815776/

Recent research has suggested that resveratrol may prevent events linked to tumor initiation.  This has attracted a lot attention towards resveratrol compared to other natural polyphenols. [75,76]. Resveratrol is an excellent scavenger of free radicals produced in the body as well as the free radicals induced by toxic metals [77]. It also protects against lipid peroxidation within cell membranes and the damaging effects on DNA resulting from reactive oxygen species (ROS) [78]. And it is suggested that  resveratrol functions as an antimutagen[79] . 

Resveratrol has been shown in preclinical studies to protect against cancer chemotherapy induced cardiac toxicity. It has also been reported to possess anticancer properties of its own to enhance the anticancer effect of other cancer treatments. Thus, they may both  protect the cardiovascular system and fight the cancer at the same time [106]. 

Resveratrol as Cardioprotective Agent

Research shows clearly that Resveratrol has anti-inflammatory effects. By downregulating inflammatory factors, RSV has improved coronary injuries from inflammation. Based on this effect, RES might show a beneficial outcome in diabetic cases with coronary heart disease in accord with its protective effects on cardiovascular tissues [105].

In 1992 the suggestion that RSV might favorably impact cardiac disease came from what became known as the ‘French paradox.’ French researchers Renaud and de Lorgeril observed  that people in France had a relatively low incidence of coronary heart disease despite consuming a diet rich in saturated fats [140] and they had a higher wine intake than  many other countries. Therefore it was hypothesized that moderate wine intake might explain this finding and that RSV (resveratrol) the antioxidant constituent of red wine, might account for this beneficial effect[141].  That initial article certainly helped spark interest in RSV and contributed to the notion that persists today that red wine might be beneficial if used in  moderation. That idea has being published many times over the years and even widely accepted among doctors. However further research into alcohol intake seems to debunk this idea. The current research consensus now is that no amount of wine (or any alcohol) is beneficial to health.  https://drsobo.com/any-alcohol-is-harmful-to-health/    As far as the ‘French paradox” is concerned  resveratrol itself, which is found in grapes is the beneficial element that makes wine look healthier than it is. A  recent news report was published asking the question https://apple.news/AZxbVXsAYReOAuGgfr2ZyZA “Is red wine good for your heart’ ?  The authors of the news item got a cardiologist to weigh in.  A cardiovascular surgeon Jeremy London from  Savannah, Georgia, had  a clear and strong opinion about it., “In a nutshell, red wine is not good for your heart,” he says, “The amount of red wine you would have to drink to get any benefit from resveratrol would be excessive.” He continued, “Resveratrol is found in the skins of grapes and in certain other plants, fruits and seeds. It is being studied in the prevention of cancer and heart disease. It is a type of antioxidant and a type of polyphenol.”

Red wine contains resveratrol and he said it “has been shown that this can cause dilation of blood vessels, make platelets slippery so that you don’t get the blockages in the arteries, but this has never really been proven in humans.”

5.2. Resveratrol in Wound Healing 

Numerous studies have suggested that resveratrol could increase wound healing [87,90,91]. Inflammation, proliferation, maturation, and remodeling are the four phases which rebuild tissue integrity after injury.  Resveratrol seems to be a promising treatment as it interacts with the healing cascade at multiple levels as shown in published studies – [87,88,89].  Resveratrol-induced vascular endothelial growth factor (VEGF) regulates tissue regeneration and revascularization in wounds. It can  inhibit the expression of the pro-inflammatory substance tumor necrosis factor-α (TNF-α), [92,93,94].  In resveratrol-treated patients the inflammatory markers  TNF-α, IL-1β, IL-6, MMP-2, -3, -9, and C-reactive protein (CRP) were shown to be reduced in published studies-[97,98,99,100].

Resveratrol’s impact on the regulation of inflammation benefits skin repair [101]. In vitro investigations showed that due to its antioxidant properties resveratrol can influence cell proliferation, ultrastructural preservation, and migration quality [102,103], whereas in vivo studies reported a significant improvement in wound healing properties [104].

Diabetes and the metabolic syndrome

The most common clinical applications of resveratrol which have been studied are type 2 diabetes mellitus and glucose control (23 studies),  followed by cardiovascular disease (21). The positive findings of preclinical research has focused on the metabolic effects of RSV and has led to a total of 39 investigations across a spectrum of cardio-metabolic disease, metabolic syndrome, NAFLD, and obesity . 

Resveratrol For Fighting Infections

Resveratrol has been reported to affect many viruses like influenza A virus by altering cellular pathways influencing viral replication itself. Epstein–Barr Virus (EBV), the agent causing mononucleosis, relates to different proliferative diseases and establishes a latent and/or a lytic infection. De Leo and co-workers [109] examined the antiviral activity of RES against the EBV replicative cycle and studied the molecular targets involved.  With this work, De Leo and co-authors constructed the basis for evaluating the antiviral activity of RES against EBV infection, envisaging the possibility to extend it to other types of infections.

It has been shown that Resveratrol can block critical pathways involved in SARS-CoV-2 pathogenesis, and body immune activation, and downregulate pro-inflammatory cytokine release.  [112,113]. Available studies may envisage that it could be a strategic adjunctive antiviral agent to use in synergy with others.

Other potential uses

Resveratrol showed a protective role in preclinical models of osteoarthritis and rheumatoid arthritis by reducing the production of pro-inflammatory  factors, and through modulation of cellular and humoral responses [81].

The general anti-inflammatory and antioxidant effects of RSV in humans  has led to trials for conditions, such as ulcerative colitis and arthritis-related diseases. Ten studies have addressed the effects of RSV on cognitive function, and three have explored its ability to modulate biomarkers of Alzheimer’s disease. [109,110]. 

Thirty five percent of all RSV studies recruited healthy volunteers; a further 9% specifically involved overweight or obese individuals who were classed as otherwise healthy.  Just over half of all RSV studies (56%) involved patients with an underlying disease or pathology . The near-even split between healthy individuals and patients with a diagnosed pathology reflects a focus on health maintenance and prevention, as well as using RSV as a potential treatment. RSV has been investigated in adults of all ages including elderly populations over 70 years, 

 One of the limitations associated with the existing clinical data is that the most have been relatively small. Few trials (5% of the total) have involved over 100 people taking RSV. Also most trials have involved a short duration of RSV administration (median 8 weeks). Six trials involved participants consuming RSV for 12 months [8,11,89,98,108,109] and in a recent small open-label dose–escalation study in 11 patients with muscular dystrophy, RSV was taken for 2 years [150]; Thus RSV must still be considered at an early stage of development in showing any clinical efficacy.  https://pmc.ncbi.nlm.nih.gov/articles/PMC6317057/

Studies have shown that RSV is well-tolerated at daily doses of less than 1,000mg [109]. 

Side effects associated with RSV were relatively minor and mostly gastrointestinal in nature- diarrhea, constipation, nausea, abdominal cramps, vomiting, heartburn, reflux, and bloating. 

RSV pharmacokinetics and metabolism have been well characterized, although there is still a need for the assessment of different dosing schedules and a greater understanding of the potential role of RSV metabolites, both human- and bacteria-derived, in contributing to any clinical efficacy.