Resveratrol (3, 4′, 5-trihydroxystilbene) is a stilbenoid class of compound and works as phytoalexin (i.e., a substance that is produced by plant tissues in response to contact with a parasite and specifically inhibits the growth of that parasite) [1]. Because of its intriguing pharmacological potential, it has recently gained a lot of study attention. Early studies have illustrated the presence of substantial amounts of Resveratrol (RVT) in wounded, infected, and UV-treated leaves [2]. It is primarily found in grapes, peanuts, and berries. In the 1940s, RVT was discovered in the white hellebore plant. It is also found in processed plant products; its presence in red wine (concentrations of 0.1–14.3 mg/L) has been proposed as a possible explanation for the “French paradox,” the observation of an unusually low rate of heart disease among Southern French people who drink a lot of red wine, despite a high saturated fat diet ^[3][4][3,4]. SIRT1, one of the mammalian versions of the sirtuin family of proteins, is activated by RVT [5], deacetylates histones and non-histone proteins, such as transcription factors [6]. Metabolism, stress resistance, cell survival, cellular senescence, inflammation-immune function, endothelial functions, and circadian rhythms are all affected by the SIRT1-regulated pathway [5]. Since RVT has been demonstrated to activate SIRT1, it is expected to help people with disorders such as improper metabolic regulation, inflammation, and cell cycle abnormalities. RVT’s usage as a nutraceutical and a therapeutic agent for a variety of disorders has been extensively investigated in preclinical trials as a natural molecule. Moreover, clinical trials are been conducted globally so as to establish its therapeutic efficacy for treatment of different diseases. A detailed description of it is mentioned in subsequent subtopics.

Because of the substantial dangers associated with standard cancer therapies, such as surgery and chemotherapy, its usage is of particular interest to cancer patients [7]. The intricacies of cancer cell signalling networks make it difficult for targeted inhibitors that target only one network to be effective. RVT, on the other hand, has been found to have chemo-preventive and chemotherapeutic effects on tumours in vitro and in vivo by targeting various pathways, making it a promising anticancer drug [8]. RVT has an effect on carcinogenesis at all three stages: initiation, promotion, and progression. Additionally, RVT has been demonstrated to directly trigger the apoptotic pathway via a variety of methods ^[9][10][9,10]. For example it has an effect on the nuclear factor κB (NF-B) signalling system, which governs inflammation, immunological response to infection, and cellular response to stimuli [11]. Furthermore, it has also been demonstrated that it blocks the IGF-1R/Akt/Wnt pathways and activates p53, influencing cell development and carcinogenesis [12]. Moreover, it can also block the PI3K/Akt pathway, which regulates cell differentiation, development, and proliferation, and other factors [13]. Several studies have been conducted to investigate the various methods by which RVT operates the PI3K/Akt pathway.

Considering its diverse potentials, an attempt has been made to advocate the development of RVT as a drug molecule. Although there are several dietary supplement products available in the global market, a thorough investigation in terms of clinical safety and efficacy may pave the way for a new therapeutic molecule.

Since resveratrol is a well-known antioxidant and has been utilised as a nutraceutical for many years, it possesses a range of therapeutic properties. As some of its clinical trials are completed, it could therefore be regarded as a promising drug candidate to be used in the treatment of certain diseases.

Dark grape extracts (Vitis vinifera) and giant knot weed (Polygonnum cuspidatum, a perennial shrub) are the richest natural sources of RVT (Table 1). It is also abundant in labrusca and muscadine grapes. Additionally, it is also found in plants such as eucalyptus, spruce, and lily, as well as in foods such as mulberries, peanuts, blueberries, strawberries, hops, and their derivatives ^[14][15][14,15]. It may also be found in the vines, roots, seeds, and stalks, but the skin has the highest concentration, with 50–100 g per gm [16]. RVT is a phytoalexin, which is a kind of antibiotic molecule generated by plants as part of their defense against diseases. For example, in reaction to an invading fungus, RVT is produced from p-coumaroyl CoA and malonyl CoA ^[1][17][1,17]. As fungal infections are more prevalent in cooler areas, grapes produced in cooler climates have a higher quantity of RVT [18]. Table 2 shows the total RVT concentration of several wines and foods. Similarly, Figure 1 shows the occurrence of RVT in different sources.

Data pertaining to marketed products have been collected from the National Institute of Health, dietary supplement label database and other websites. These items include either RVT or a combination of RVT. These items have a great variation of doses, such as 20 mg per serving to 1400 mg. It indicates a better safety profile of the molecule.

RVT has also been studied clinically, such as assessment of the effect of RVT on cognitive and cerebral blood flow in the United Kingdom. In Canada, an analysis on the effect of antioxidants on cardio vascular risk was assessed. Furthermore, in Brazil the RVT was examined for its effectiveness in the management of pain due to endometriosis. Moreover, in Taiwan the effect of RVT on complications in patients with haemodialysis was investigated. Additionally, RVT with or without Piperine to enhance the plasma level of RVT was also assessed (USA). Meanwhile, in Singapore, a phase-1 trial is being conducted to analyse the effect of RVT in patients with Type-2 Diabetes (RED). The impact of RVT on brain function and structure was also studied. Moreover, in Italy, RVT’s anti-inflammatory and antioxidants effects on healthy adults were examined. In Tamil Nadu (India), RVT was evaluated as a potent supplement for patient with Type-2 Diabetes Mellitus. Likewise, a similar study was conducted in Maharashtra (India) to confirm whether the addition of RVT is beneficial and safe for patient with diabetes, dyslipidemia and hypertension (who are already on standard therapy). In Karnataka (India), the effect of nutritional supplementation of RVT on patients with advanced cancers and undergoing chemotherapy was evaluated. A similar trial was conducted in Maharashtra (India), to study the effects of nutritional supplementation of extremely active RVT (XAR) in healthy human individuals. In Maharashtra, effect of RVT and copper in reducing toxic side-effects of chemotherapy in patients with advanced mouth cancer was analysed. A similar trial was held in Maharashtra (India), to study the effect of RVT-copper in reducing oral mucositis in patients receiving concurrent chemo radiotherapy for locally advanced oropharyngeal cancer. Additionally, a similar trial was performed in Maharashtra (India) to assess the effect of the addition of RVT with chemotherapeutic agents in patients with gastric cancer. Likewise, the effect of RVT-copper on treating COVID-19 pneumonia was analysed in Maharashtra (India). Additionally, a study to assess the effect of oral RVT and copper combination on life span of glioblastoma patients undergoing surgery was conducted in Maharashtra (India). In Australia, RVT as an option for the treatment of Friedreich ataxia was assessed. A study of dietary RVT on glucose and lipid metabolism disorder is being conducted in China. In Australia, the effect of RVT on circulatory function of obese people with elevated blood pressure was examined. Another trial on similar lines was conducted in Australia where the sustained effect of RVT on circulatory functions in obese adults were assessed. Additionally, the role of RVT in the prevention of colorectal polyps was also investigated in Australia. Moreover, the effect of RVT’s supplementation on gut hormone secretion, gastric emptying and blood glucose responses to meals in patients with type-2 diabetes was assessed in Australia. Meanwhile, another study on RVT supplementation on cerebrovascular function, mood and cognitive performance in type-2 diabetes mellitus (T2DM) was completed in Australia. Another clinical trial was executed in Australia to establish whether RVT can enhance mood, physical function and cerebrovascular function and counteract cognitive decline in post-menopausal women. In Germany, the bioavailability of three different RVT products was evaluated in healthy individuals. Likewise, a similar study was also conducted in Germany, to examine the bioavailability and metabolism of RVT as a constituent of berries in humans. Furthermore, a biokinetic study on the impact of formulation on RVT bioavailability was also performed in Germany. More details about clinical trials are mentioned in Table 3.

The medicinal advantages and other beneficial features of RVT have drawn the attention of numerous researchers to investigate and develop some intellectual property in the form of patents; some of them are included in Table 46.