Introductory Chapter: Resveratrol – Recent Advances, Application, and Therapeutic Potential

1. Introduction

Owing to its conceivable health advantages, resveratrol has received a great deal of interest lately. One such is the “French paradox,” where despite the French population’s excessive consumption of saturated fat, red wine drinking, which has a high resveratrol concentration, has been related to reduced cardiovascular disease mortality in the population. Since then, resveratrol has been the subject of extensive research aimed at a range of diverse health-beneficial impacts, which include however are not restricted to those related to anti-obesity, anti-inflammation, cardiovascular protection, antidiabetes type 2, anti-aging, anti-carcinogenesis, and neuroprotection [1]. Resveratrol has undergone significant research on a wide range of illnesses, but it has also been tested for its ability to fight against germs and fungi. The stilbene family of naturally stirring polyphenolic antioxidants includes resveratrol (3,5,4′-trihydroxystilbene). Resveratrol is a hydroxylated derivative of a stilbene with a C6-C2-C6 carbon skeleton (1,2- diphenylethylene). Numerous plants, including grapevines (Vitis vinifera), blueberries, cranberries (Vaccinium spp.), and peanuts (Arachis hypogea), as well as traditional Asian herbal medicines, contain resveratrol. However, grapevines are the primary natural source for human consumption. Resveratrol is a naturally up phytoalexin that a plant produces when they are damaged by fungus or ultraviolet (UV) rays [2]. As evidenced by the Botrytis cinerea fungus, the cause of gray mold. According to Jeandet et al. [3], the production of resveratrol is more common in the grapes that are not infected but are in close proximity to grapevines that have been infected with a fungus. This mechanism helps in inhibiting the spread of infection to the healthy grapes. Both a cis and a trans isomer of resveratrol exist; the opposite geometric isomer is the supplementary predominant arrangement in red wine and is the subject of the utmost research because of its higher bioavailability and increased stability. Overall, red wine has more resveratrol than white wine. Trans-resveratrol levels in red wine can range from 1.9 mg/L on average to 14.3 mg/L, according to Stervbo et al. [4]. Over twenty proteins in eukaryotic species interact with the promiscuous chemical resveratrol. Resveratrol has the ability to attach itself to the F1-domain of bovine ATP synthase, specifically within a small space located between a β-subunit and the γ-subunit, as demonstrated by crystallization complexes [5]. The maintenance of the Mitochondrial ATPase or ATP synthase residues implies that Escherichia coli has a comparable binding site for resveratrol. In E. coli, a facultative aerobe, resveratrol has the ability to bind to ATP synthase in a reversible manner. This binding process leads to a partial obstruction of both ATP hydrolysis and synthesis.

2. Therapeutic application

Resveratrol lowers the metabolic rate of Arcobacter spp. and inhibits Mycobacterium smegmatis’s hydrolysis of Adenosine triphosphate. Resveratrol administration to E. coli chambers decreases the growth of fermentable glucose and prohibits development of the non-fermentable source of carbon succinate, which indicates that resveratrol suppresses oxidative phosphorylation. According to Boogerd et al. [6], the growth of E. coli mutants lacking ATP synthase can still occur in the presence of fermentable carbon sources such as glucose, pyruvate, or lactate. This suggests that ATP synthase alone cannot be the sole target responsible for inhibiting growth in E. coli. Furthermore, in E. coli, resveratrol induces DNA fragmentation and leads to the upregulation of the SOS stress-response regulon. Yet, growth suppression is not a direct result of DNA fragmentation or the elevation of the SOS stress response. The cellular multiplication machinery is also impacted by resveratrol due to the elongation of resveratrol-treated E. coli cells, which happens when ftsZ expression is suppressed. Resveratrol is considered to obstruct FtsZ-mediated septum formation and cellular replication since FtsZ is a crucial protein in septum synthesis throughout cellular replication. Subramanian et al. [7] found that resveratrol administration was associated with cell membrane damage because it enhanced potassium leakage and propidium iodide absorption. Whereas Staphylococcus aureus Nohr-Meldgaard et al. [8] found no evidence of resveratrol-induced membrane damage. Numerous human investigations have shown that after oral administration, resveratrol exhibits significant absorption but limited bioavailability of unaltered resveratrol. Following oral treatment, resveratrol is easily metabolized; sulfate- and glucuronide-resveratrol conjugates achieve plasma concentrations that are 3–8 times greater than those of free resveratrol. Following a single oral dose of 5 g of trans-resveratrol, the peak plasma concentration of resveratrol reached 539 ng/mL after 1.5 hours. However, the average plasma concentration decreased to approximately 52 ng/mL after 24 hours. Similarly, to this, after taking 1 g of resveratrol orally, the average plasma concentration was 73 ng/mL. Given the inhibitory doses required, the systemic application of resveratrol for the treatment of infections caused by bacteria is restricted by the limited bioavailability of orally given resveratrol. It could be intriguing to look into the antibacterial qualities of such conjugates given that in humans, resveratrol undergoes rapid metabolism, resulting in higher levels of resveratrol conjugates in the bloodstream compared to the unmodified form of the molecule. The effects of resveratrol administered intravenously (IV) in humans have also been studied, but the directed dosage was small, being 0.2 mg, and it was rapidly metabolized, suggesting that i.v. resveratrol administration might have limited, if any, anti-microbial uses for systemic diseases. Furthermore, the application of resveratrol topically offers the potential to utilize concentrations that have a beneficial effect against numerous infectious diseases, as suggested by Zhou et al. [9].

3. Conclusion

In the nutshell, the resveratrol holds medicinal and preservative activity mainly attributed to its strong antioxidant potential. Moreover, it showed the tendency to be used in the formulation of different functional products. Furthermore, more human-based efficacy trials are suggested to unveil its true therapeutic potential.